Consensus on managing center-involving diabetic macular edema in Hong Kong: perspective
Keywords:Angiopoietin-2, Intravitreal injections, Laser therapy, Vascular endothelial growth factors, Visual acuity
Diabetic macular edema is a common cause of vision loss in the working-age population, and its prevalence is increasing in Asian countries. Managing diabetic macular edema encompasses effective control of systemic factors and intraocular treatment including anti-vascular endothelial growth factor therapy, corticosteroid implants, and laser photocoagulation. Based on several guidelines and the available evidence, we present consensus on managing diabetic macular edema in Hong Kong to ensure optimal anatomical and visual outcomes. Although anti-vascular endothelial growth factor agents are recommended first-line treatment for patients with diabetic macular edema experiencing vision loss; however, the frequent dosing regimen imposes great clinical and patient burden. Longer-acting anti-vascular endothelial growth factor agents are needed to allow forendothelial longer intervals between treatments. As demonstrated in the KITE and KESTREL studies, brolucizumab, an antivascular endothelial growth factor A agent, is associated with fewer cases of intraretinal or subretinal fluid than aflibercept, despite fewer injections. Similarly, faricimab, a bispecific antibody targeting both vascular endothelial growth factor A and angiopoietin-2, demonstrated comparable vision gains with longer treatment intervals and larger improvements in anatomical outcome in the YOSEMITE and RHINE trials. Early intensive antivascular endothelial growth factor therapy leads to greater improvements in visual acuity and anatomical outcomes. Patients who respond inadequately to anti-vascular endothelial growth factor therapy, as monitored by optical coherence tomography, should switch treatment modality.
Bressler N, Chan CKM, Wong IY, et al. Optimizing management of diabetic macular edema in Hong Kong: a collaborative position paper. Hong Kong J Ophthalmol 2017;21:59-64.
Cheung GC, Yoon YH, Chen LJ, et al. Diabetic macular oedema: evidence-based treatment recommendations for Asian countries. Clin Exp Ophthalmol 2018;46:75-86.
Furino C, Boscia F, Reibaldi M, Alessio G. Intravitreal therapy for diabetic macular edema: an update. J Ophthalmol 2021;2021:6654168.
Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica 2017;237:185-222.
Browning DJ, Stewart MW, Lee C. Diabetic macular edema: evidence-based management. Indian J Ophthalmol 2018;66:1736-50.
Urias EA, Urias GA, Monickaraj F, McGuire P, Das A. Novel therapeutic targets in diabetic macular edema: beyond VEGF. Vision Res 2017;139:221-7.
Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 2015;372:1193-203.
EURETINA. 2020 Clinical Survey Outcomes. Accessed October 3, 2022. Available at: https://eplatform.euretina.org//app/uploads/2021/09/EURETINA-Clinical-Outcomes-2020.pdf.
Wykoff CC, Garweg JG, Regillo C, et al. Brolucizumab for treatment of diabetic macular edema (DME): 100-week results from the KESTREL and KITE studies. Invest Ophthalmol Vis Sci 2022;63:3849.
Ferrone PJ, Wykof CC, Tadayoni R, et al. Efficacy and safety of faricimab in diabetic macular edema: one-year results from the phase 3 YOSEMITE and RHINE trials. Presented at: American Academy of Ophthalmology 2021; New Orleans, Louisiana, USA.
Sung JJ, Chiu PW, Chan FKL, et al. Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018. Gut 2018;67:1757-68.
Daruich A, Matet A, Moulin A, et al. Mechanisms of macular edema: beyond the surface. Prog Retin Eye Res 2018;63:20-68.
Bandello F, Battaglia Parodi M, Lanzetta P, et al. Diabetic macular edema. Dev Ophthalmol 2017;58:102-38.
Grant MB, Afzal A, Spoerri P, Pan H, Shaw LC, Mames RN. The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs 2004;13:1275-93.
Gohil R, Crosby-Nwaobi R, Forbes A, Burton B, Hykin P, Sivaprasad S. Caregiver burden in patients receiving ranibizumab therapy for neovascular age related macular degeneration. PLoS One 2015;10:e0129361.
Ciulla TA, Hussain RM, Pollack JS, Williams DF. Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: a real-world analysis of 49 485 eyes. Ophthalmol Retina 2020;4:19-30.
Ciulla TA, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes. Br J Ophthalmol 2021;105:216-221.
Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Maguire MG, Martin DF, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology 2016;123:1751-61.
Lingam G, Wong TY. Systemic medical management of diabetic retinopathy. Middle East Afr J Ophthalmol 2013;20:301-8.
Makaroff L. Advocating for Improved Treatment and Outcomes for Diabetic Macular Edema. Presented at: Diabetic Macular Edema Internal Expert Summit; June 2022, 2014, Paris, France.
Sharma S, Karki P, Joshi SN, Parajuli S. Optical coherence tomography patterns of diabetic macular edema and treatment response to bevacizumab: a short-term study. Ther Adv Ophthalmol 2022;14:25158414221074519.
Pieramici D, Singh RP, Gibson A, et al. Outcomes of diabetic macular edema eyes with limited early response in the VISTA and VIVID studies. Ophthalmol Retina 2018;2:558-66.
Cai S, Bressler NM. Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Curr Opin Ophthalmol 2017;28:636-43.
Li YF, Ren Q, Sun CH, et al. Efficacy and mechanism of anti-vascular endothelial growth factor drugs for diabetic macular edema patients. World J Diabetes 2022;13:532-42.
Adamis AP, Brittain CJ, Dandekar A, Hopkins JJ. Building on the success of anti-vascular endothelial growth factor therapy: a vision for the next decade. Eye (Lond) 2020;34:1966-72.
Madjedi K, Pereira A, Ballios BG, et al. Switching between anti-VEGF agents in the management of refractory diabetic macular edema: a systematic review. Surv Ophthalmol 2022;67:1364-72.
Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology 2016;123:1351-9.
Chen JT, Chen LJ, Chen SN, et al. Management of diabetic macular edema: experts’ consensus in Taiwan. Jpn J Ophthalmol 2020;64:235-42.
Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID studies. Ophthalmology 2016;123:2376-85.
Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 2012;119:789-801.
Arevalo JF, Sanchez JG, Wu L, et al. Primary intravitreal bevacizumab for diffuse diabetic macular edema: the Pan-American Collaborative Retina Study Group at 24 months. Ophthalmology 2009;116:1488-97.
Rajendram R, Fraser-Bell S, Kaines A, et al. A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol 2012;130:972-9.
Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 2010;117:1078-86.e2.
Diabetic Retinopathy Clinical Research Network, Scott IU, Edwards AR, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114:1860-7.
Regillo C. Brolucizumab for the treatment of DME: 100-week results from the two pivotal Phase III KESTREL and KITE studies. Presented at: Angiogenesis, Exudation and Degeneration annual meeting 2022; February11-12, 2022; Miami, Florida, United States.
Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology 2015;122:2044-52.
Regula JT, Lundh von Leithner P, Foxton R, et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol Med 2016;8:1265-88.
Loukovaara S, Robciuc A, Holopainen JM, et al. Ang-2 upregulation correlates with increased levels of MMP-9, VEGF, EPO and TGFβ1 in diabetic eyes undergoing vitrectomy. Acta Ophthalmol 2013;91:531-9.
ClinicalTrials.gov. A study to evaluate the long-term safety and tolerability of faricimab in participants with diabetic macular edema. Accessed October 3, 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT04432831.
National Institute for Health and Care Excellence. Brolucizumab for treating diabetic macular oedema. Accessed January 8, 2023. Available at: https://www.nice.org.uk/guidance/ta820.
National Institute for Health and Care Excellence. Faricimab for treating diabetic macular oedema. Accessed January 8, 2023. Available at: https://www.nice.org.uk/guidance/ta799/resources/faricimab-for-treating-diabetic-macular-oedema-pdf-82611625700293.
National Institute for Health and Care Excellence. Ranibizumab for treating diabetic macular oedema. Accessed January 8, 2023. Available at: https://www.nice.org.uk/guidance/ta274/resources/ranibizumab-for-treating-diabetic-macular-oedema-pdf-82600612458181.
National Institute for Health and Care Excellence. Aflibercept for treating diabetic macular oedema. Accessed January 8, 2023.Available at: https://www.nice.org.uk/guidance/ta346/resources/aflibercept-for-treating-diabetic-macular-oedema-pdf-82602611201221.
Pharmaceutical Benefits Advisory Committee. Meeting outcomes May 2022 PBAC Intracycle Meeting. Accessed October 3, 2022. Available at: https://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2022-05/May-2022-PBAC-Web-Outcomes.pdf.
Pharmaceutical Benefits Advisory Committee. Meeting outcomes March 2021 PBAC Meeting. Accessed January 5, 2023. Available at: https://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2021-03/march-2021-pbac-web-outcomes.pdf.
Avery RL, Gordon GM. Systemic safety of prolonged monthly anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis. JAMA Ophthalmol 2016;134:21-9.
Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 2010;117:1064-77.e35.
Brown DM, Nguyen QD, Marcus DM, et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 2013;120:2013-22.
Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology 2014;121:2247-54.
Boyer DS, Nguyen QD, Brown DM, asu K, Ehrlich JS; RIDE and RISE Research Group. Outcomes with as-needed ranibizumab after initial monthly therapy: long-term outcomes of the phase III RIDE and RISE trials. Ophthalmology 2015;122:2504-13.e1.
Baker CW, Glassman AR, Beaulieu WT, et al. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial. JAMA 2019;321:1880-94.
Rush RB, Rush SW. Faricimab for treatment-resistant diabetic macular edema. Clin Ophthalmol 2022;16:2797-801.
Perente I, Alkin Z, Ozkaya A, et al. Focal laser photocoagulation in non-center involved diabetic macular edema. Med Hypothesis Discov Innov Ophthalmol 2014;3:9-16.
Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 2014;121:1904-14.
Khalane L, Alkunte A, Birajdar A. Sustained release drug delivery system: a concise review. Accessed November 4, 2022. Available at: https://www.pharmatutor.org/articles/sustained-release-drug-delivery-system-concise-review#:~:text=There%20are%20several%20advantages%20of%20sustained%20release%20drug,costs%20through%20improved%20therapy%20and%20shorter%20treatment%20period.
Maturi RK, Glassman AR, Liu D, et al. Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: a DRCR Network phase 2 randomized clinical trial. JAMA Ophthalmol 2018;136:29-38.
Diabetic Retinopathy Clinical Research Network. The course of response to focal/grid photocoagulation for diabetic macular edema. Retina 2009;29:1436-43.
Relhan N, Flynn HW Jr. The Early Treatment Diabetic Retinopathy Study historical review and relevance to today’s management of diabetic macular edema. Curr Opin Ophthalmol 2017;28:205-12.
Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA 2015;314:2137-46.
Kulikov AN, Sosnovskii SV, Berezin RD, Maltsev DS, Oskanov DH, Gribanov NA. Vitreoretinal interface abnormalities in diabetic macular edema and effectiveness of anti-VEGF therapy: an optical coherence tomography study. Clin Ophthalmol 2017;11:1995-2002.
Flikier S, Wu A, Wu L. Revisiting pars plana vitrectomy in the primary treatment of diabetic macular edema in the era of pharmacological treatment. Taiwan J Ophthalmol 2019;9:224-32.
Hsieh TC, Deng GH, Chang YC, Chang FL, He MS. A real-world study for timely assessing the diabetic macular edema refractory to intravitreal anti-VEGF treatment. Front Endocrinol (Lausanne) 2023;14:1108097.
Huang CH, Yang CH, Hsieh YT, Yang CM, Ho TC, Lai TT. Hyperreflective foci in predicting the treatment outcomes of diabetic macular oedema after anti-vascular endothelial growth factor therapy. Sci Rep 2021;11:5103.
Ophir A, Martinez MR, Mosqueda P, Trevino A. Vitreous traction and epiretinal membranes in diabetic macular oedema using spectral-domain optical coherence tomography. Eye (Lond) 2010;24:1545-53.
Ivastinovic D, Haas A, Weger M, et al. Vitrectomy for diabetic macular edema and the relevance of external limiting membrane. BMC Ophthalmol 2021;21:334.
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