Continuous Delivery of Ranibizumab Via the Port Delivery System for Proliferative Diabetic Retinopathy-related Vitreous Hemorrhage With Pars Plana Vitrectomy and Limited PRP.

Summary

In Prolifertive Diabetic Retinopathy eyes with bleeding known as vitreous hemorrhage (VH) requiring a surgical procedure to remove the vitreous, called a vitrectomy, we will determine if the benefit and safety of adding a small implant that will be filled with medication called Susvimo is better with limited laser treatment.

Timeline

Start

2026-09

Primary completion

2029-09

Completion

2029-12

Publications

• Background Centers for Disease Control and Prevention (CDC). State-specific incidence of diabetes among adults--participating states, 1995-1997 and 2005-2007. MMWR Morb Mortal Wkly Rep. 2008 Oct 31;57(43):1169-73.
• Background International Diabetes Federation: Facts and figures. Accessed 26 September 2016, 1612-1613
• Background Varma R, Bressler NM, Doan QV, Gleeson M, Danese M, Bower JK, Selvin E, Dolan C, Fine J, Colman S, Turpcu A. Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol. 2014 Nov;132(11):1334-40. doi: 10.1001/jamaophthalmol.2014.2854.
• Background Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012 Mar 29;366(13):1227-39. doi: 10.1056/NEJMra1005073. No abstract available.
• 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 Klein R, Klein BE, Moss SE. A population-based study of diabetic retinopathy in insulin-using patients diagnosed before 30 years of age. Diabetes Care. 1985 Sep-Oct;8 Suppl 1:71-6. doi: 10.2337/diacare.8.1.s71.
• Background Sivaprasad S, Prevost AT, Vasconcelos JC, Riddell A, Murphy C, Kelly J, Bainbridge J, Tudor-Edwards R, Hopkins D, Hykin P; CLARITY Study Group. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. Lancet. 2017 Jun 3;389(10085):2193-2203. doi: 10.1016/S0140-6736(17)31193-5. Epub 2017 May 7.
• Background Gross JG, Glassman AR, Liu D, Sun JK, Antoszyk AN, Baker CW, Bressler NM, Elman MJ, Ferris FL 3rd, Gardner TW, Jampol LM, Martin DF, Melia M, Stockdale CR, Beck RW; Diabetic Retinopathy Clinical Research Network. Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2018 Oct 1;136(10):1138-1148. doi: 10.1001/jamaophthalmol.2018.3255.
• Background Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.
• Background Obeid A, Su D, Patel SN, Uhr JH, Borkar D, Gao X, Fineman MS, Regillo CD, Maguire JI, Garg SJ, Hsu J. Outcomes of Eyes Lost to Follow-up with Proliferative Diabetic Retinopathy That Received Panretinal Photocoagulation versus Intravitreal Anti-Vascular Endothelial Growth Factor. Ophthalmology. 2019 Mar;126(3):407-413. doi: 10.1016/j.ophtha.2018.07.027. Epub 2018 Aug 2.
• Background Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, Jhaveri CD, Punjabi OS, Salehi-Had H, Wells JA 3rd, Maguire MG, Stockdale CR, Martin DF, Sun JK; DRCR Retina Network. Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2020 Dec 15;324(23):2383-2395. doi: 10.1001/jama.2020.23027.
• Background Pieramici DJ, Awh CC, Chang M, Emanuelli A, Holekamp NM, Hu AY, Suner IJ, Wykoff CC, Brittain C, Howard D, Quezada-Ruiz C, Santhanakrishnan A, Latkany P. Port Delivery System With Ranibizumab vs Monitoring in Nonproliferative Diabetic Retinopathy Without Macular Edema: The Pavilion Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):317-325. doi: 10.1001/jamaophthalmol.2025.0001.
• Background Khanani AM, Campochiaro PA, Graff JM, Marcus DM, Miller D, Mittra RA, Regillo C, Sheth VS, Bobbala A, Gune S, Lin S, Quezada-Ruiz C, Malhotra V. Continuous Ranibizumab via Port Delivery System vs Monthly Ranibizumab for Treatment of Diabetic Macular Edema: The Pagoda Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):326-335. doi: 10.1001/jamaophthalmol.2025.0006.
• Background Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic Retinopathy Vitrectomy Study report 2. The Diabetic Retinopathy Vitrectomy Study Research Group. Arch Ophthalmol. 1985 Nov;103(11):1644-52.
• Background Ho T, Smiddy WE, Flynn HW Jr. Vitrectomy in the management of diabetic eye disease. Surv Ophthalmol. 1992 Nov-Dec;37(3):190-202. doi: 10.1016/0039-6257(92)90137-i.
• Background El Annan J, Carvounis PE. Current management of vitreous hemorrhage due to proliferative diabetic retinopathy. Int Ophthalmol Clin. 2014 Spring;54(2):141-53. doi: 10.1097/IIO.0000000000000027.
• 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 Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.
• Background Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.
• Background Heier JS, Korobelnik JF, Brown DM, Schmidt-Erfurth U, Do DV, Midena E, Boyer DS, Terasaki H, Kaiser PK, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Vitti R, Berliner AJ, Zeitz O, Metzig C, Holz FG. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies. Ophthalmology. 2016 Nov;123(11):2376-2385. doi: 10.1016/j.ophtha.2016.07.032. Epub 2016 Sep 17.
• Background Wong TY, Haskova Z, Asik K, Baumal CR, Csaky KG, Eter N, Ives JA, Jaffe GJ, Korobelnik JF, Lin H, Murata T, Ruamviboonsuk P, Schlottmann PG, Seres AI, Silverman D, Sun X, Tang Y, Wells JA, Yoon YH, Wykoff CC; YOSEMITE and RHINE Investigators. Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials. Ophthalmology. 2024 Jun;131(6):708-723. doi: 10.1016/j.ophtha.2023.12.026. Epub 2023 Dec 28.
• Background Bressler SB, Liu D, Glassman AR, Blodi BA, Castellarin AA, Jampol LM, Kaufman PL, Melia M, Singh H, Wells JA; Diabetic Retinopathy Clinical Research Network. Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab. JAMA Ophthalmol. 2017 Jun 1;135(6):558-568. doi: 10.1001/jamaophthalmol.2017.0821.
• Background Figueira J, Fletcher E, Massin P, Silva R, Bandello F, Midena E, Varano M, Sivaprasad S, Eleftheriadis H, Menon G, Amaro M, Ayello Scheer S, Creuzot-Garcher C, Nascimento J, Alves D, Nunes S, Lobo C, Cunha-Vaz J; EVICR.net Study Group. Ranibizumab Plus Panretinal Photocoagulation versus Panretinal Photocoagulation Alone for High-Risk Proliferative Diabetic Retinopathy (PROTEUS Study). Ophthalmology. 2018 May;125(5):691-700. doi: 10.1016/j.ophtha.2017.12.008. Epub 2018 Feb 1.
• Background Diabetic Retinopathy Clinical Research Network*. Randomized clinical trial evaluating intravitreal ranibizumab or saline for vitreous hemorrhage from proliferative diabetic retinopathy. JAMA Ophthalmol. 2013 Mar;131(3):283-93. doi: 10.1001/jamaophthalmol.2013.2015.
• Background Marcus, D., Singh, H., Starnes, D., Walia, H., Farooq, A., & Frazier, H. et al. Endolaserless Vitrectomy With Intravitreal Aflibercept Injection for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage (LASER LESS TRIAL). Journal Of Vitreoretinal Diseases 2018; 2(3), 127-137
• Background D'Amico, D.. From the Editor-in-Chief. Journal Of Vitreoretinal Diseases 2018;2(3), 125-126.
• Background Zhao XY, Xia S, Chen YX. Antivascular endothelial growth factor agents pretreatment before vitrectomy for complicated proliferative diabetic retinopathy: a meta-analysis of randomised controlled trials. Br J Ophthalmol. 2018 Aug;102(8):1077-1085. doi: 10.1136/bjophthalmol-2017-311344. Epub 2017 Dec 15.
• Background Maguire MG, Liu D, Glassman AR, Jampol LM, Johnson CA, Baker CW, Bressler NM, Gardner TW, Pieramici D, Stockdale CR, Sun JK; DRCR Retina Network. Visual Field Changes Over 5 Years in Patients Treated With Panretinal Photocoagulation or Ranibizumab for Proliferative Diabetic Retinopathy. JAMA Ophthalmol. 2020 Mar 1;138(3):285-293. doi: 10.1001/jamaophthalmol.2019.5939.
• Background Marcus D. Endolaserless Vitrectomy with Intravitreal Aflibercept Injection (IAI) for Proliferative Diabetic Retinopathy (PDR)-Related Vitreous Hemorrhage: 1 Year Results (LASER LESS TRIAL). Presented at the annual meeting of the American Society of Retina Specialists (ASRS). Vancouver, Canada, July, 2018.
• Background Kasetty VM, Starnes DC, Sood N, Qin LG, Moses MM, Frazier HK, Singh H, Marcus DM. Complications, Compliance, and 3-Year Outcomes After Endolaserless Vitrectomy With Aflibercept Monotherapy for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage. Ophthalmic Surg Lasers Imaging Retina. 2023 Feb;54(2):89-96. doi: 10.3928/23258160-20221216-02. Epub 2023 Feb 1.
• Background Levy R, Marcus DM. Complications, Compliance and 2 Year Outcomes after Endolaserless Vitrectomy with Aflibercept Monotherapy for PDR-Related Vitreous Hemorrhage. Presented virtually at the Association of Research in Vision and Ophthalmology (ARVO) meeting. May, 2020
• Background Marcus DM, Taylor C, Starnes, D, et al. Ultra wide-field fluorescein angiographic-guided aflibercept (WFFAGA) monotherapy for proliferative diabetic retinopathy (PDR). J. Clin. Ophthalmol. 2019;3(2):197-204.
• Background Wubben TJ, Johnson MW; Anti-VEGF Treatment Interruption Study Group. Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Retinopathy: Consequences of Inadvertent Treatment Interruptions. Am J Ophthalmol. 2019 Aug;204:13-18. doi: 10.1016/j.ajo.2019.03.005. Epub 2019 Mar 13.
• Background Gao X, Obeid A, Aderman CM, Talcott KE, Ali FS, Adam MK, Rovner BW, Hyman L, Ho AC, Hsu J. Loss to Follow-up After Intravitreal Anti-Vascular Endothelial Growth Factor Injections in Patients with Diabetic Macular Edema. Ophthalmol Retina. 2019 Mar;3(3):230-236. doi: 10.1016/j.oret.2018.11.002. Epub 2018 Nov 10.
• Background Bressler SB, Beaulieu WT, Glassman AR, Gross JG, Melia M, Chen E, Pavlica MR, Jampol LM; Diabetic Retinopathy Clinical Research Network. Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Factors Associated with Vision and Edema Outcomes. Ophthalmology. 2018 Nov;125(11):1776-1783. doi: 10.1016/j.ophtha.2018.04.039. Epub 2018 Jul 3.
• Background Campochiaro PA, Marcus DM, Awh CC, Regillo C, Adamis AP, Bantseev V, Chiang Y, Ehrlich JS, Erickson S, Hanley WD, Horvath J, Maass KF, Singh N, Tang F, Barteselli G. The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial. Ophthalmology. 2019 Aug;126(8):1141-1154. doi: 10.1016/j.ophtha.2019.03.036. Epub 2019 Apr 1.
• Background Holekamp NM, Campochiaro PA, Chang MA, Miller D, Pieramici D, Adamis AP, Brittain C, Evans E, Kaufman D, Maass KF, Patel S, Ranade S, Singh N, Barteselli G, Regillo C; all Archway Investigators. Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2022 Mar;129(3):295-307. doi: 10.1016/j.ophtha.2021.09.016. Epub 2021 Sep 29.

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Indications