Combined Ranibizumab and Iluvien for Diabetic Macular Oedema

Summary

This trial investigated whether adding Iluvien sustained release steroid intravitreal eye implant at the beginning of regular anti-VEGF (anti Vascular Endothelial Growth Factor) intravitreal eye injection treatment for diabetic macular oedema would improve disease stability and reduce the need for regular anti-VEGF intravitreal eye injections over first two years. Diabetic macular oedema, accumulation of microscopic fluid at the back of the eye, is a major cause of poor vision in patients with diabetes. This is a double mask randomized control multisite trial, to be conducted at 10 NHS hospital eye clinics in England.

Timeline

Start

2019-09-01

Primary completion

2022-09-01

Completion

2023-09-01

Publications

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• Background Moss SE, Klein R, Klein BE. The 14-year incidence of visual loss in a diabetic population. Ophthalmology. 1998 Jun;105(6):998-1003. doi: 10.1016/S0161-6420(98)96025-0.
• Background Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012 Mar;35(3):556-64. doi: 10.2337/dc11-1909. Epub 2012 Feb 1.
• Background Virgili G, Parravano M, Menchini F, Evans JR. Anti-vascular endothelial growth factor for diabetic macular oedema. Cochrane Database Syst Rev. 2014 Oct 24;(10):CD007419. doi: 10.1002/14651858.CD007419.pub4.
• Background Grover D, Li TJ, Chong CC. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005656. doi: 10.1002/14651858.CD005656.pub2.
• Background Goni FJ, Stalmans I, Denis P, Nordmann JP, Taylor S, Diestelhorst M, Figueiredo AR, Garway-Heath DF. Elevated Intraocular Pressure After Intravitreal Steroid Injection in Diabetic Macular Edema: Monitoring and Management. Ophthalmol Ther. 2016 Jun;5(1):47-61. doi: 10.1007/s40123-016-0052-8. Epub 2016 May 10.
• Background Parrish RK 2nd, Campochiaro PA, Pearson PA, Green K, Traverso CE; FAME Study Group. Characterization of Intraocular Pressure Increases and Management Strategies Following Treatment With Fluocinolone Acetonide Intravitreal Implants in the FAME Trials. Ophthalmic Surg Lasers Imaging Retina. 2016 May 1;47(5):426-35. doi: 10.3928/23258160-20160419-05.
• Background Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2003 Sep;110(9):1690-6. doi: 10.1016/S0161-6420(03)00568-2.
• Background Funatsu H, Yamashita H, Sakata K, Noma H, Mimura T, Suzuki M, Eguchi S, Hori S. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology. 2005 May;112(5):806-16. doi: 10.1016/j.ophtha.2004.11.045.
• Background Aiello LP. Angiogenic pathways in diabetic retinopathy. N Engl J Med. 2005 Aug 25;353(8):839-41. doi: 10.1056/NEJMe058142. No abstract available.
• Background 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 Aug;31(8):1541-6. doi: 10.1248/bpb.31.1541.
• Background Minassian DC, Owens DR, Reidy A. Prevalence of diabetic macular oedema and related health and social care resource use in England. Br J Ophthalmol. 2012 Mar;96(3):345-9. doi: 10.1136/bjo.2011.204040. Epub 2011 May 20.
• Background Arevalo JF, Lasave AF, Wu L, Acon D, Farah ME, Gallego-Pinazo R, Alezzandrini AA, Fortuna V, Quiroz-Mercado H, Salcedo-Villanueva G, Maia M, Serrano M, Rojas S; Pan-American Collaborative Retina Study Group (PACORES). Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan-American Collaborative Retina Study group. Br J Ophthalmol. 2016 Dec;100(12):1605-1610. doi: 10.1136/bjophthalmol-2015-307950. Epub 2016 Feb 24.
• Background Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, Brucker AJ, Ferris FL, Hampton GR, Jhaveri C, Melia M, Beck RW; Diabetic Retinopathy Clinical Research Network. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016 Jun;123(6):1351-9. doi: 10.1016/j.ophtha.2016.02.022. Epub 2016 Feb 27.
• Background Mehta H, Gillies M, Fraser-Bell S. Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema. Ther Adv Chronic Dis. 2015 Sep;6(5):234-45. doi: 10.1177/2040622315590319.
• Background Hernandez-Bel L, Cervera-Taulet E, Navarro-Palop C, Castro-Navarro V, Chiarri-Toumit C, Montero-Hernandez J. Sequential Dexamethasone and Aflibercept Treatment in Patients with Diabetic Macular Edema: Structural and Functional Outcomes at 52 Weeks. Ophthalmologica. 2019;241(2):98-104. doi: 10.1159/000489345. Epub 2018 Jul 11.
• Background Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, Garretson B, Gupta A, Hariprasad SM, Bailey C, Reichel E, Soubrane G, Kapik B, Billman K, Kane FE, Green K; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012 Oct;119(10):2125-32. doi: 10.1016/j.ophtha.2012.04.030. Epub 2012 Jun 21.
• Background Cunha-Vaz J, Ashton P, Iezzi R, Campochiaro P, Dugel PU, Holz FG, Weber M, Danis RP, Kuppermann BD, Bailey C, Billman K, Kapik B, Kane F, Green K; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous implants: long-term benefit in patients with chronic diabetic macular edema. Ophthalmology. 2014 Oct;121(10):1892-903. doi: 10.1016/j.ophtha.2014.04.019. Epub 2014 Jun 14.
• Background Shimura M, Yasuda K, Minezaki T, Noma H. Reduction in the frequency of intravitreal bevacizumab administrations achieved by posterior subtenon injection of triamcinolone acetonide in patients with diffuse diabetic macular edema. Jpn J Ophthalmol. 2016 Sep;60(5):401-7. doi: 10.1007/s10384-016-0458-9. Epub 2016 Jun 15.
• Background Prunte C, Fajnkuchen F, Mahmood S, Ricci F, Hatz K, Studnicka J, Bezlyak V, Parikh S, Stubbings WJ, Wenzel A, Figueira J; RETAIN Study Group. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016 Jun;100(6):787-95. doi: 10.1136/bjophthalmol-2015-307249. Epub 2015 Oct 9.

Drugs

Indications