The South African macular oedema in diabetics study (the same study): a prospective randomized non-inferiority trial
Background: Diabetic retinopathy is the most common cause of visual loss affecting the economically productive age group globally. Diabetic macular oedema (DMO) results from leakage of fluid into the retinal interstitial space. Anti-vascular endothelial growth factor (anti-VEGF) drugs are the first line treatment for DMO. Since monthly injections are required, this treatment regimen can prove very costly. Of the anti-VEGF drugs, bevacizumab is the most cost-effective. The pro re nata (PRN) method is the current standard of care. However, the treat and extend (T and E) regimen can potentially decrease the patient burden on hospitals. Thus far, no randomised clinical trials have been performed using Bevacizumab in a treat and extend versus pro re nata regimen.
Methods: A prospective randomised non-inferiority clinical trial testing bevacizumab (1.25 mg) in a treat and extend method versus the pro re nata method is being conducted. Patients will be randomised using a simple computer-based randomised algorithm. The primary outcome is non-inferiority within a five-letter margin for the T and E regimen versus the PRN regimen.
Conclusions: This study aims to inform a key area in the literature on the treatment of DMO, i.e. whether a T and E regimen is non-inferior to a PRN regimen in the treatment of DMO with bevacizumab, which is the only anti VEGF available in resource poor settings. It is motivated by the cost involved in the treatment of DMO as well as the treatment burden on both the patient and the health institution at which the patient is receiving treatment.
Trial registration: The trial has been registered on the Pan-African clinical trials registry (PACTR202001624880-753).
Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus- present and future perspectives. Nat Rev Endocrinol. 2012;8(4):228-36.
Klein BEK. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007;14(4):179-83.
Ford JA, Lois N, Royle P, Clar C, Shyangdan D, Waugh N. Current treatments in diabetic macular oedema: systematic review and meta-analysis. BMJ Open. 2013;3(3).
Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol Chic Ill 1960. 1985;103(12):1796-806.
Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, et al. Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmol. 2010;117(11):2146-51.
Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmol. 2016;123(6):1351-9.
Grover DA, Li T, Chong CC. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2008. Available at: http://www.cochrane-library.com/cdsr/doi/10.1002/14651858.CD005656.pub2/full. Accessed on 17 August 2020.
Anti‐vascular endothelial growth factor for diabetic macular oedema: a network meta‐analysis - Virgili, G 2018. Cochrane Library. 2018. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007419.pub6/full. Accessed on 17 August, 2020.
Romero-Aroca P, Riva-Fernandez S de la, Valls-Mateu A, Sagarra-Alamo R, Moreno-Ribas A, Soler N, et al. Cost of diabetic retinopathy and macular oedema in a population, an eight year follow up. BMC Ophthalmol. 2016;16(1):1-7.
Resnikoff S, Lansingh VC, Washburn L, Felch W, Gauthier T-M, Taylor HR, et al. Estimated number of ophthalmologists worldwide (International Council of Ophthalmology update): will we meet the needs? Br J Ophthalmol. 2020 ;104(4):588-92.
Chin-Yee D, Eck T, Fowler S, Hardi A, Apte RS. A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration. Br J Ophthalmol. 2015;100(7):914-7.
Prünte C, Fajnkuchen F, Mahmood S, Ricci F, Hatz K, Studnička J, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016;100(6):787-95.
Main Place. Statistics South Africa. Available at: http://www.statssa.gov.za/?page_id=4286&id=11317. Accessed on 17 August, 2020.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-81.
Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye Lond Engl. 2013;27(7):78794.
Kornblau IS, El-Annan JF. Adverse reactions to fluorescein angiography: A comprehensive review of the literature. Surv Ophthalmol. 2019;64(5):679-93.
Maniadakis N, Konstantakopoulou E. Cost Effectiveness of Treatments for Diabetic Retinopathy: A Systematic Literature Review. PharmacoEconomics. 2019;37(8):995-1010.
Senra H, Ali Z, Balaskas K, Aslam T. Psychological impact of anti-VEGF treatments for wet macular degeneration-a review. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2016;254(10):1873-80.