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The dexamethasone drug delivery system: Indications and evidence

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An Erratum to this article was published on 12 June 2013

Abstract

Introduction

The Ozurdex® (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 μg of preservativefree dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options.

Methods

Published data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed.

Results

The dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management.

Conclusions

The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.

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References

  1. Leopold IH. Nonsteroidal and steroidal antiinflammatory agents. In: Sears M, Tarkkanen A, eds. Surgical pharmacology of the eye. New York: Raven Press, 1985:83–133.

    Google Scholar 

  2. Nauck M, Karakiulakis G, Perruchoud A, et al. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Euro J Pharmacol. 1998;341:309–315.

    Article  CAS  Google Scholar 

  3. Woods AC. The present status of ACTH and cortisone in clinical ophthalmology. Am J Ophthalmol. 1951;34:945–960.

    PubMed  CAS  Google Scholar 

  4. Mc LJ, Gordon DM, Koteen H. Clinical experiences with ACTH and cortisone in ocular diseases. Trans Am Acad Ophthalmol Otolaryngol. 1951;55:565–572.

    Google Scholar 

  5. Gordon DM, McLean JM. Effects of pituitary adrenocorticotropic hormone (ACTH) therapy in ophthalmologic conditions. JAMA. 1950;142:1271–1276.

    Google Scholar 

  6. Leopold IH, Purnell JE, Cannon EJ, Steinmetz CG, Mc DP. Local and systemic cortisone in ocular disease. Am J Ophthalmol. 1951;34:361–371.

    PubMed  CAS  Google Scholar 

  7. Scheie HG, Tyner GS, Buesseler JA, Alfano JE. Adrenocorticotropic hormone ACTH and cortisone in ophthalmology; report of cases. AMA Arch Ophthalmol. 1951;45:301–316.

    PubMed  CAS  Google Scholar 

  8. Fitzgerald JR, Bellows JG, Donegan JM, et al. Early clinical results of ACTH and cortisone treatment of ocular diseases. AMA Arch Ophthalmol. 1951;45:320–323.

    PubMed  CAS  Google Scholar 

  9. Weijtens O, Feron EJ, Schoemaker RC, et al. High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection. Am J Ophthalmol. 1999;128:192–197.

    Article  PubMed  CAS  Google Scholar 

  10. Weijtens O, Schoemaker RC, Cohen AF, et al. Dexamethasone concentration in vitreous and serum after oral administration. Am J Ophthalmol. 1998;125:673–679.

    Article  PubMed  CAS  Google Scholar 

  11. Weijtens O, Schoemaker RC, Lentjes EG, Romijn FP, Cohen AF, van Meurs JC. Dexamethasone concentration in the subretinal fluid after a subconjunctival injection, a peribulbar injection, or an oral dose. Ophthalmology. 2000;107:1932–1938.

    Article  PubMed  CAS  Google Scholar 

  12. Weijtens O, Schoemaker RC, Romijn FP, Cohen AF, Lentjes EG, van Meurs JC. Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. Ophthalmology. 2002;109:1887–1891.

    Article  PubMed  Google Scholar 

  13. Tano Y, Chandler D, Machemer R. Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. Am J Ophthalmol. 1980;90:810–816.

    PubMed  CAS  Google Scholar 

  14. Tano Y, Sugita G, Abrams G, Machemer R. Inhibition of intraocular proliferations with intravitreal corticosteroids. Am J Ophthalmol. 1980;89:131–136.

    PubMed  CAS  Google Scholar 

  15. Conti SM, Kertes PJ. The use of intravitreal corticosteroids, evidence-based and otherwise. Curr Opin Ophthalmol. 2006;17:235–244.

    Article  PubMed  Google Scholar 

  16. Penfold PL, Wen L, Madigan MC, Gillies MC, King NJ, Provis JM. Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration. Clin Exp Immunol. 2000;121:458–465.

    Article  PubMed  CAS  Google Scholar 

  17. Singer KL, Stevenson BR, Woo PL, Firestone GL. Relationship of serine/threonine phosphorylation/ dephosphorylation signaling to glucocorticoid regulation of tight junction permeability and ZO-1 distribution in nontransformed mammary epithelial cells. J Biol Chem. 1994;269:16108–16115.

    PubMed  CAS  Google Scholar 

  18. Sherif Z, Pleyer U. Corticosteroids in ophthalmology: past-present-future. Ophthalmologica. 2002;216:305–315.

    Article  PubMed  Google Scholar 

  19. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW. Penn State Retina Research Group. Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Diabetes. 1998;47:1953–1959.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Edelman JL, Lutz D, Castro MR. Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood aqueous barrier breakdown. Exp Eye Res. 2005;80:249–258.

    Article  PubMed  CAS  Google Scholar 

  22. Grosser T, Smyth EM, FitzGerald GA. Antiinflammatory, Antipyritic, and Analgesic Agents; Pharmacology of Gout. In: Brunton L, Chabner B, Knollmann B. eds. Goodman and Gilman’s Pharmacological Basis of Therapeutics. 12th edition. New York: McGraw-Hill Professional: 2010:959–1004.

    Google Scholar 

  23. Nabih M, Peyman GA, Tawakol ME, Naguib K. Toxicity of high-dose intravitreal dexamethasone. Int Ophthalmol. 1991;15:233–235.

    Article  PubMed  CAS  Google Scholar 

  24. Kwak HW, D’Amico DJ. Evaluation of the retinal toxicity and pharmacokinetics of dexamethasone after intravitreal injection. Arch Ophthalmol. 1992;110:259–266.

    PubMed  CAS  Google Scholar 

  25. Maxwell DP, Jr., Brent BD, Diamond JG, Wu L. Effect of intravitreal dexamethasone on ocular histopathology in a rabbit model of endophthalmitis. Ophthalmology 1991;98:1370–1375.

    PubMed  Google Scholar 

  26. Narayanan R, Mungcal JK, Kenney MC, Seigel GM, Kuppermann BD. Toxicity of triamcinolone acetonide on retinal neurosensory and pigment epithelial cells. Invest Ophthalmol Vis Sci. 2006;47:722–728.

    Article  PubMed  Google Scholar 

  27. Yeung CK, Chan KP, Chan CK, Pang CP, Lam DS. Cytotoxicity of triamcinolone on cultured human retinal pigment epithelial cells: comparison with dexamethasone and hydrocortisone. Jpn J Ophthalmol. 2004;48:236–242.

    Article  PubMed  CAS  Google Scholar 

  28. Yu SY, Damico FM, Viola F, D’Amico DJ, Young LH. Retinal toxicity of intravitreal triamcinolone acetonide: a morphological study. Retina. 2006;26:531–536.

    Article  PubMed  Google Scholar 

  29. Graham RO, Peyman GA. Intravitreal injection of dexamethasone. Treatment of experimentally induced endophthalmitis. Arch Ophthalmol. 1974;92:149–154.

    PubMed  CAS  Google Scholar 

  30. Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of the sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci. 2011;52:80–86.

    Article  PubMed  Google Scholar 

  31. Haller JA, Kuppermann BD, Blumenkranz MS, et al. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol. 2010;128:289–296.

    Article  PubMed  CAS  Google Scholar 

  32. Haller JA, Bandello F, Belfort R, Jr., et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117:1134–1146, e1133.

    Article  PubMed  Google Scholar 

  33. Ip MS, Scott IU, VanVeldhuisen PC, et al. 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. 2009;127:1101–1114.

    Article  PubMed  Google Scholar 

  34. Scott IU, Ip MS, VanVeldhuisen PC, et al. 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. 2009;127:1115–1128.

    Article  PubMed  Google Scholar 

  35. Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1102–1112,e1101.

    Article  PubMed  Google Scholar 

  36. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1124–1133,e1121.

    Article  PubMed  Google Scholar 

  37. Bressler NM, Schachat AP. Management of macular edema from retinal vein occlusions: you can never have too many choices. Ophthalmology. 2010;117:1061–1063.

    Article  PubMed  Google Scholar 

  38. Williams GA, Haller JA, Kuppermann BD, et al. Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol. 2009;147:1048–54,1054.e 1–2.

    Article  PubMed  CAS  Google Scholar 

  39. Boyer, D for the OZURDEX™ CHAMPLAIN Study Group. Open-label phase IIIb study of dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Presented at the 33rd Annual Macular Society Meeting; February 24, 2010; Tucson, Arizona, USA.

  40. Yanyali A, Nohutcu AF, Horozoglu F, Celik E. Modified grid laser photocoagulation versus pars plana vitrectomy with internal limiting membrane removal in diabetic macular edema. Am J Ophthalmol. 2005;139:795–801.

    Article  PubMed  Google Scholar 

  41. Schindler RH, Chandler D, Thresher R, Machemer R. The clearance of intravitreal triamcinolone acetonide. Am J Ophthalmol. 1982;93:415–417.

    PubMed  CAS  Google Scholar 

  42. 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.

    Article  PubMed  Google Scholar 

  43. Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB 3rd, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology. 2003;110:681–686.

    Article  PubMed  Google Scholar 

  44. Yanyali A, Aytug B, Horozoglu F, Nohutcu AF. Bevacizumab (Avastin) for diabetic macular edema in previously vitrectomized eyes. Am J Ophthalmol. 2007;144:124–126.

    Article  PubMed  CAS  Google Scholar 

  45. Lowder C, Belfort R Jr., Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011; Jan 10 [Epub ahead of print].

  46. Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92:467–471.

    PubMed  CAS  Google Scholar 

  47. Mangione CM, Berry S, Spritzer K, et al. Identifying the content area for the 51-item National Eye Institute Visual Function Questionnaire: results from focus groups with visually impaired persons. Arch Ophthalmol. 1998;116:227–233.

    PubMed  CAS  Google Scholar 

  48. Kupperman, B. Safety and efficacy of dexamethasone intravitreal implant as adjunctive therapy to Lucentis neovascularization secondary to age-related macular degeneration. Presented at the 33rd Annual Macular Society Meeting; February 24, 2010; Tucson, Arizona, USA.

  49. Patelli F, Fasolino G, Radice P, et al. Time course of changes in retinal thickness and visual acuity after intravitreal triamcinolone acetonide for diffuse diabetic macular edema with and without previous macular laser treatment. Retina. 2005;25:840–845.

    Article  PubMed  Google Scholar 

  50. Cardillo JA, Melo LA Jr., Costa RA, et al. Comparison of intravitreal versus posterior sub-Tenon’s capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology. 2005;112:1557–1563.

    Article  PubMed  Google Scholar 

  51. Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. Intravitreal injection versus sub-Tenon’s infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial. Invest Ophthalmol Vis Sci. 2005;46:3845–3849.

    Article  PubMed  Google Scholar 

  52. Larsson J, Zhu M, Sutter F, Gillies MC. Relation between reduction of foveal thickness and visual acuity in diabetic macular edema treated with intravitreal triamcinolone. Am J Ophthalmol. 2005;139:802–806.

    Article  PubMed  Google Scholar 

  53. Ozdemir H, Karacorlu M, Karacorlu SA. Regression of serous macular detachment after intravitreal triamcinolone acetonide in patients with diabetic macular edema. Am J Ophthalmol. 2005;140:251–255.

    Article  PubMed  CAS  Google Scholar 

  54. Ozkiris A, Erkilic K. Complications of intravitreal injection of triamcinolone acetonide. Can J Ophthalmol. 2005;40:63–68.

    PubMed  Google Scholar 

  55. Moshfeghi AA, Scott IU, Flynn HW Jr., Puliafito CA. Pseudohypopyon after intravitreal triamcinolone acetonide injection for cystoid macular edema. Am J Ophthalmol. 2004;138:489–492.

    Article  PubMed  CAS  Google Scholar 

  56. Roth DB, Chieh J, Spirn MJ, Green SN, Yarian DL, Chaudhry NA. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol. 2003;121:1279–1282.

    Article  PubMed  Google Scholar 

  57. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115:1447–1459.e10.

    Article  Google Scholar 

  58. Ober MD, Barile GR, Tari SR, Tosi GM, Schiff WM, Chang S. Measurement of the actual dose of triamcinolone acetonide delivered by common techniques of intravitreal injection. Am J Ophthalmol. 2006;142:597–600.

    Article  PubMed  CAS  Google Scholar 

  59. Shaikh S, Ho S, Engelmann LA, Klemann SW. Cell viability effects of triamcinolone acetonide and preservative vehicle formulations. Br J Ophthalmol. 2006;90:233–236.

    Article  PubMed  CAS  Google Scholar 

  60. Chang YS, Wu CL, Tseng SH, Kuo PY, Tseng SY. Cytotoxicity of triamcinolone acetonide on human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007;48:2792–2798.

    Article  PubMed  Google Scholar 

  61. Chang YS, Wu CL, Tseng SH, Kuo PY, Tseng SY. In vitro benzyl alcohol cytotoxicity: implications for intravitreal use of triamcinolone acetonide. Exp Eye Res. 2008;86:942–950.

    Article  PubMed  CAS  Google Scholar 

  62. Kamppeter B, Cej A, Jonas J. Intraocular concentration of triamcinolone acetonide after intravitreal injection in the rabbit eye. Ophthalmology 2008;115:1372–1375.

    Article  PubMed  Google Scholar 

  63. Bakri SJ, Snyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ. Pharmacokinetics of intravitreal ranibizumab. Ophthalmology. 2007;114:2179–2182.

    Article  PubMed  Google Scholar 

  64. Center for Drug Evaluation and Research. Summary Review for application NDA. Application number 22–315. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022315s000_SumR.pdf Accessed March 22, 2011.

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Authors and Affiliations

  1. Retina Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Nikolas J. S. London, Allen Chiang & Julia A. Haller

  2. Wills Eye Institute, 840 Walnut Street, Suite 1510, Philadelphia, PA, USA

    Julia A. Haller

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  1. Nikolas J. S. London
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  2. Allen Chiang
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  3. Julia A. Haller
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Correspondence to Julia A. Haller.

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An erratum to this article is available at http://dx.doi.org/10.1007/s12325-013-0035-2.

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London, N.J.S., Chiang, A. & Haller, J.A. The dexamethasone drug delivery system: Indications and evidence. Adv Therapy 28, 351–366 (2011). https://doi.org/10.1007/s12325-011-0019-z

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