Pharmacology of corticosteroids for diabetic macular edema

Investigative Ophthalmology and Visual Science

Volumn 59, Issue 1, 2018, Pages 1-12

  Whitcup, Scott M ^a   Cidlowski, John A ^b   Csaky, Karl G ^c   Ambati, Jayakrishna ^d  

^a JULES STEIN EYE INSTITUTE   (United States)

^b NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^c RETINA FOUNDATION OF THE SOUTHWEST   (United States)

^d UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Corticosteroids; Drug differentiation; Intravitreal drug delivery; Retinal disease

Indexed keywords

CORTICOSTEROID; CYTOCHROME P450; CYTOKINE; DEXAMETHASONE; FLUOCINOLONE ACETONIDE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MONOCYTE CHEMOTACTIC PROTEIN 1; PREDNISOLONE; TRIAMCINOLONE ACETONIDE; VASCULOTROPIN A; GLUCOCORTICOID;

CARDIAC MUSCLE CELL; CENTRAL RETINA VEIN OCCLUSION; DIABETIC MACULAR EDEMA; DIABETIC RETINOPATHY; DOWN REGULATION; DRUG DELIVERY SYSTEM; DRUG POTENCY; DRUG SOLUBILITY; GENE ACTIVATION; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE INACTIVATION; HEART FAILURE; HEART VENTRICLE HYPERTROPHY; LEUKOSTASIS; MACULAR DEGENERATION; PRIORITY JOURNAL; RETINA ISCHEMIA; REVIEW; UPREGULATION; UVEITIS; COMPLICATION; HUMAN; INTRAVITREAL DRUG ADMINISTRATION; MACULAR EDEMA;

DIABETIC RETINOPATHY; DRUG DELIVERY SYSTEMS; GLUCOCORTICOIDS; HUMANS; INTRAVITREAL INJECTIONS; MACULAR EDEMA;

EID: 85040221859     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.17-22259     Document Type: Review

References (80)

1. Hench PS, Kendall EC, Slocumb CH, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorti-costerone: compound E) and of pituitary adrenocortical hormone in arthritis: preliminary report. Ann Rheum Dis. 1949;8:97–104.
2. Hench PS, Kendall EC, Slocumb CH, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorti-costerone; compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Staff Meet Mayo Clin. 1949;24:181–197.
3. Duke-Elder S, Perkins ES. System of Ophthalmology Vol IX, Diseases of the Uveal Tract. London: Henry Kimpton Publishers; 1966:176.
4. Kasper DL, Fauci AS, Hauser S, Longo D, Jameson JL, Loscalzo J. Harrison’s Principles of Internal Medicine. 19th ed. New York: McGraw Hill Professional; 2015.
5. Nussenblatt RB, Whitcup SM. Uveitis Fundamentals and Clinical Practice. 4th ed. Elsevier Health Sciences; 2010.
6. Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002;96: 23–43.
7. Edelman JL. Differentiating intraocular glucocorticoids. Ophthalmologica. 2010;224(suppl 1):25–30.
8. Knollman BC. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011.
9. Kamppeter BA, Cej A, Jonas JB. Intraocular concentration of triamcinolone acetonide after intravitreal injection in the rabbit eye. Ophthalmology. 2008;115:1372–1375.
10. Yang Y, Bailey C, Loewenstein A, Massin P. Intravitreal corticosteroids in diabetic macular edema: pharmacokinetic considerations. Retina. 2015;35:2440–2449.
11. Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci. 2011;52:80–86.
12. Chang-Lin JE, Burke JA, Peng Q, et al. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vi- trectomized and nonvitrectomized eyes. Invest Ophthalmol Vis Sci. 2011;52:4605–4609.
13. Allergan, Inc. Ozurdex Prescribing Information. 2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/la bel/2014/022315s010lbl.pdf. Accessed April 2015.
14. Kane FE, Green KE. Ocular pharmacokinetics of fluocinolone acetonide following Iluvien implantation in the vitreous humor of rabbits. J Ocul Pharmacol Ther. 2015;31:11–16.
15. 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;20:269–275.
16. Meireles A, Goldsmith C, El-Ghrably I, et al. Efficacy of 0.2 lg/ day fluocinolone acetonide implant (ILUVIEN) in eyes with diabetic macular edema and prior vitrectomy. Eye (Lond). 2017;31:684–690.
17. Campochiaro PA, Nguyen QD, Hafiz G, et al. Aqueous levels of fluocinolone acetonide after administration of fluocinolone acetonide inserts or fluocinolone acetonide implants. Ophthalmology. 2013;120:583–587.
18. Campochiaro PA, Hafiz G, Shah SM, et al. Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert. Ophthalmology. 2010;117:1393–1399.e3.
19. Bausch & Lomb. Retisert Prescribing Information. 2012. Available at: http://www.bausch.com/Portals/77/-/m/BL/United%20States/Files/Package%20Inserts/Pharma/retisert-pre scribing-information.pdf. Accessed December 10, 2017.
20. Yilmaz T, Cordero-Coma M, Federici TJ. Pharmacokinetics of triamcinolone acetonide for the treatment of macular edema. Expert Opin Drug Metab Toxicol. 2011;7:1327–1335.
21. Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB III, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology. 2003;110:681–686.
22. Audren F, Tod M, Massin P, et al. Pharmacokinetic-pharmaco-dynamic modeling of the effect of triamcinolone acetonide on central macular thickness in patients with diabetic macular edema. Invest Ophthalmol Vis Sci. 2004;45:3435–3441.
23. Chin HS, Park TS, Moon YS, Oh JH. Difference in clearance of intravitreal triamcinolone acetonide between vitrectomized and nonvitrectomized eyes. Retina. 2005;25:556–560.
24. Zacharias LC, Lin T, Migon R, et al. Assessment of the differences in pharmacokinetics and pharmacodynamics between four distinct formulations of triamcinolone acetonide. Retina. 2013;33:522–531.
25. Chen H, Sun S, Li J, et al. Different intravitreal properties of three triamcinolone formulations and their possible impact on retina practice. Invest Ophthalmol Vis Sci. 2013;54:2178– 2185.
26. Bhagat R, Zhang J, Farooq S, Li XY. Comparison of the release profile and pharmacokinetics of intact and fragmented dexamethasone intravitreal implants in rabbit eyes. J Ocul Pharmacol Ther. 2014;30:854–858.
27. Trotter JL, Garvey WF. Prolonged effects of large-dose methylprednisolone infusion in multiple sclerosis. Neurology. 1980;30:702–708.
28. Beck RW, Cleary PA, Anderson MM Jr, et al.; for the The Optic Neuritis Study Group. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med. 1992;326:581–588.
29. Perandones CE, Illera VA, Peckham D, Stunz LL, Ashman RF. Regulation of apoptosis in vitro in mature murine spleen T cells. J Immunol. 1993;151:3521–3529.
30. Migita K, Eguchi K, Kawabe Y, et al. Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy. Transplantation. 1997;63:583–587.
31. Andreau K, Lemaire C, Souvannavong V, Adam A. Induction of apoptosis by dexamethasone in the B cell lineage. Immuno-pharmacology. 1998;40:67–76.
32. Druilhe A, Letuve S, Pretolani M. Glucocorticoid-induced apoptosis in human eosinophils: mechanisms of action. Apoptosis. 2003;8:481–495.
33. Gelati M, Corsini E, De Rossi M, et al. Methylprednisolone acts on peripheral blood mononuclear cells and endothelium in inhibiting migration phenomena in patients with multiple sclerosis. Arch Neurol. 2002;59:774–780.
34. Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects. Ann Rheum Dis. 1989;48:662– 666.
35. Buttgereit F, Scheffold A. Rapid glucocorticoid effects on immune cells. Steroids. 2002;67:529–534.
36. Jewell CM, Scoltock AB, Hamel BL, Yudt MR, Cidlowski JA. Complex human glucocorticoid receptor dim mutations define glucocorticoid induced apoptotic resistance in bone cells. Mol Endocrinol. 2012;26:244–256.
37. Oakley RH, Ren R, Cruz-Topete D, et al. Essential role of stress hormone signaling in cardiomyocytes for the prevention of heart disease. Proc Natl Acad Sci U S A. 2013;110:17035– 17040.
38. Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol. 2013;132:1033–1044.
39. Hadley KE, Louw A, Hapgood JP. Differential nuclear localisation and promoter occupancy play a role in glucocorticoid receptor ligand-specific transcriptional responses. Steroids. 2011;76:1176–1184.
40. Fan BJ, Wang DY, Tham CC, Lam DS, Pang CP. Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone. Invest Ophthalmol Vis Sci. 2008;49:1886–1897.
41. Nehmé A, Lobenhofer EK, Stamer WD, Edelman JL. Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. BMC Med Genomics. 2009;2:58.
42. Schaaf MJ, Cidlowski JA. Molecular determinants of glucocorticoid receptor mobility in living cells: the importance of ligand affinity. Mol Cell Biol. 2003;23:1922–1934.
43. Schaaf MJ, Lewis-Tuffin LJ, Cidlowski JA. Ligand-selective targeting of the glucocorticoid receptor to nuclear subdo-mains is associated with decreased receptor mobility. Mol Endocrinol. 2005;19:1501–1515.
44. Fine BS, Brucker AJ. Macular edema and cystoid macular edema. Am J Ophthalmol. 1981;92:466–481.
45. Yanoff M, Fine BS, Brucker AJ, Eagle RC Jr. Pathology of human cystoid macular edema. Surv Ophthalmol. 1984; 28(suppl):505–511.
46. Funatsu H, Noma H, Mimura T, Eguchi S, Hori S. Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology. 2009;116:73–79.
47. Dong N, Xu B, Wang B, Chu L. Study of 27 aqueous humor cytokines in patients with type 2 diabetes with or without retinopathy. Mol Vis. 2013;19:1734–1746.
48. Rajab HA, Baker NL, Hunt KJ, et al. The predictive role of markers of inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes. J Diabetes Complications. 2015;29:108–114.
49. Skala MC, Riching KM, Gendron-Fitzpatrick A, et al. In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precan-cerous epithelia. Proc Natl Acad Sci U S A. 2007;104:19494– 19499.
50. Schweitzer D, Deutsch L, Klemm M, et al. Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy. J Biomed Opt. 2015;20:61106.
51. Burton JL, Kehrli ME Jr, Kapil S, Horst RL. Regulation of L-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone. J Leukoc Biol. 1995; 57:317–325.
52. Mizuno S, Nishiwaki A, Morita H, Miyake T, Ogura Y. Effects of periocular administration of triamcinolone acetonide on leukocyte-endothelium interactions in the ischemic retina. Invest Ophthalmol Vis Sci. 2007;48:2831–2836.
53. Miyamoto K, Khosrof S, Bursell SE, et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci U S A. 1999;96:10836–10841.
54. Lutty GA, Cao J, McLeod DS. Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid. Am J Pathol. 1997;151:707–714.
55. Lutty GA. Effects of diabetes on the eye. Invest Ophthalmol Vis Sci. 2013;54:ORSF81–ORSF87.
56. Yao XL, Cowan MJ, Gladwin MT, Lawrence MM, Angus CW, Shelhamer JH. Dexamethasone alters arachidonate release from human epithelial cells by induction of p11 protein synthesis and inhibition of phospholipase A2 activity. J Biol Chem. 1999;274:17202–17208.
57. Uckermann O, Kutzera F, Wolf A, et al. The glucocorticoid triamcinolone acetonide inhibits osmotic swelling of retinal glial cells via stimulation of endogenous adenosine signaling. J Pharmacol Exp Ther. 2005;315:1036–1045.
58. Pannicke T, Iandiev I, Wurm A, et al. Diabetes alters osmotic swelling characteristics and membrane conductance of glial cells in rat retina. Diabetes. 2006;55:633–639.
59. Nagelhus EA, Veruki ML, Torp R, et al. Aquaporin-4 water channel protein in the rat retina and optic nerve: polarized expression in Muller cells and fibrous astrocytes. J Neurosci. 1998;18:2506–2519.
60. Salaria S, Chana G, Caldara F, et al. Microarray analysis of cultured human brain aggregates following cortisol exposure: implications for cellular functions relevant to mood disorders. Neurobiol Dis. 2006;23:630–636.
61. Keil JM, Liu X, Antonetti DA. Glucocorticoid induction of occludin expression and endothelial barrier requires transcription factor p54 NONO. Invest Ophthalmol Vis Sci. 2013; 54:4007–4015.
62. Wang K, Wang Y, Gao L, Li X, Li M, Guo J. Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008;31:1541– 1546.
63. Wurm A, Lipp S, Pannicke T, et al. Involvement of A(1) adenosine receptors in osmotic volume regulation of retinal glial cells in mice. Mol Vis. 2009;15:1858–1867.
64. Aveleira CA, Lin CM, Abcouwer SF, Ambrosio AF, Antonetti DA. TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability. Diabetes. 2010;59:2872–2882.
65. Stewart EA, Saker S, Amoaku WM. Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro. Exp Eye Res. 2016; 151:75–81.
66. Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol. 2011;152:686–694.
67. Campochiaro PA, Hafiz G, Mir TA, et al. Pro-permeability factors in diabetic macular edema; the Diabetic Macular Edema Treated With Ozurdex Trial. Am J Ophthalmol. 2016; 168:13–23.
68. Gonzalez VH, Campbell J, Holekamp NM, et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of Protocol I data. Am J Ophthalmol. 2016;172:72–79.
69. Lazic R, Lukic M, Boras I, et al. Treatment of anti-vascular endothelial growth factor-resistant diabetic macular edema with dexamethasone intravitreal implant. Retina. 2014;34: 719–724.
70. Alimera Sciences. Iluvien Prescribing Information. 2016. Available at: http://www.alimerasciences.com/wp-content/uploads/2016/02/Prescribing-Information.pdf. Accessed September 15, 2017.
71. Kim MW, Moon H, Yang SJ, Joe SG. Effect of posterior subtenon triamcinolone acetonide injection on diabetic macular edema refractory to intravitreal bevacizumab injection. Korean J Ophthalmol. 2016;30:25–31.
72. Schmit-Eilenberger VK. A novel intravitreal fluocinolone acetonide implant (Iluvien®) in the treatment of patients with chronic diabetic macular edema that is insufficiently responsive to other medical treatment options: a case series. Clin Ophthalmol. 2015;9:801–811.
73. Zucchiatti I, Lattanzio R, Querques G, et al. Intravitreal dexamethasone implant in patients with persistent diabetic macular edema. Ophthalmologica. 2012;228:117–122.
74. Augustin AJ, Kuppermann BD, Lanzetta P, et al. Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: subgroup analysis of the MEAD study. BMC Ophthalmol. 2015;15:150.
75. Tan H, Wang W, Yin X, Li Y, Yin R. Identification of a selective glucocorticoid receptor ligand for the treatment of chronic inflammation in type 2 diabetes mellitus. Exp Ther Med. 2014;8:1111–1114.
76. Harcken C, Riether D, Liu P, et al. Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate. ACS Med Chem Lett. 2014;5:1318–1323.
77. Quinn MA, Cidlowski JA. Endogenous hepatic glucocorticoid receptor signaling coordinates sex-biased inflammatory gene expression. FASEB J. 2016;30:971–982.
78. Loukovaara S, Piippo N, Kinnunen K, et al. NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy [published online ahead of print March 8, 2017]. Acta Ophthalmol. doi:10.1111/aos.13427.
79. Paugh SW, Bonten EJ, Savic D, et al. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells. Nat Genet. 2015;47:607–614.
80. Kupperman BD. Differentiating steroid delivery systems for macular edema. Adv Stud Ophthalmol. 2010;7:35–41.