Brolucizumab and faricimab as new treatment options for diabetic macular edema: perspective


  • Ho Lam Wong Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR
  • Nicholas Siu Kay FUNG Department of Ophthalmology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR
  • Alvin Kwan Ho Kwok Dept. of OphthalmologyHK Sanatorium and Hospital


Brolucizumab, Diabetic retinopathy, Faricimab, Macular edema


Diabetic macular edema (DME) is the leading cause of blindness in the working populations, with patients requiring 10.7 intravitreal injections of anti- vascular endothelial growth factor (VEGF) agents per year. The high rate of non-compliance of anti-VEGF injection in patients with DME and the unmet need in current regimen may result in suboptimal visual outcome. Brolucizumab, an antibody fragment anti-VEGF-A agent, has been approved to treat neovascular age-related macular degeneration, as illustrated in the HAWK and HARRIER trials. Similarly, the KESTREL and KITE DME trials have shown that brolucizumab 6 mg achieves greater improvement in best-corrected visual acuity and greater reduction in central subfield thickness at week 52, compared with aflibercept 2 mg. Fewer patients with brolucizumab have intraretinal and subretinal fluid. Careful monitoring, prompt diagnosis, and timely intervention enable early management of adverse effects including intraocular inflammation and retinal artery occlusion. Moreover, in the BOULEVARD trial, patients with DME on faricimab 1.5 and 6.0 mg have demonstrated greater gain in Early Treatment Diabetic Retinopathy Study letters and greater reduction in central subfield thickness, compared with patients on ranibizumab 0.3 mg. The YOSEMITE and RHINE trials have demonstrated greater improvement in best-corrected visual acuity and two-step Diabetic Retinopathy Severity Scale at week 52 after faricimab 6 mg than after aflibercept 2 mg. Thus, brolucizumab and faricimab are efficacious, durable, and well tolerated, with improved treatment outcome and patient compliance.


Romero-Aroca P. Managing diabetic macular edema: the leading cause of diabetes blindness. World J Diabetes 2011;2:98-104.

Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 2021;128:1580-91.

Chauhan MZ, Rather PA, Samarah SM, Elhusseiny AM, Sallam AB. Current and novel therapeutic approaches for treatment of diabetic macular edema. Cells 2022;11:1950.

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.

Jansen ME, Krambeer CJ, Kermany DS, et al. Appointment compliance in patients with diabetic macular edema and exudative macular degeneration. Ophthalmic Surg Lasers Imaging Retina 2018;49:186-90.

Sivaprasad S, Oyetunde S. Impact of injection therapy on retinal patients with diabetic macular edema or retinal vein occlusion. Clin Ophthalmol 2016;10:939-46.

Ramakrishnan MS, Yu Y, VanderBeek BL. Visit adherence and visual acuity outcomes in patients with diabetic macular edema: a secondary analysis of DRCRnet Protocol T. Graefes Arch Clin Exp Ophthalmol 2021;259:1419-25.

Angermann R, Rauchegger T, Nowosielski Y, et al. Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism. Acta Ophthalmol 2021;99:e869-e875.

Payne JF, Wykoff CC, Clark WL, et al. Randomized trial of treat and extend ranibizumab with and without navigated laser for diabetic macular edema: TREX-DME 1 year outcomes. Ophthalmology 2017;124:74-81.

Sheth JU, Gopal L, Gillies M, et al. Vitreoretinal Society of India practice pattern survey 2020: medical retina. Indian J Ophthalmol 2021;69:1430-9.

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;105:216-21.

Tan GS, Cheung N, Simó R, Cheung GCM, Wong TY. Diabetic macular oedema. Lancet Diabetes Endocrinol 2017;5:143-55.

Nicolo M, Ferro Desideri L, Vagge A, Traverso CE. Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases. Expert Opin Investig Drugs 2021;30:193-200.

Browning DJ, Stewart MW, Lee C. Diabetic macular edema: evidence-based management. Indian J Ophthalmol 2018;66:1736-50.

Roberts PK, Vogl WD, Gerendas BS, et al. Quantification of fluid resolution and visual acuity gain in patients with diabetic macular edema using deep learning: a post hoc analysis of a randomized clinical trial. JAMA Ophthalmol 2020;138:945-53.

Massin P, Bandello F, Garweg JG, et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010;33:2399-405.

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.

Bressler SB, Ayala AR, Bressler NM, et al. Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol 2016;134:278-85.

Tadayoni R, Sararols L, Weissgerber G, Verma R, Clemens A, Holz FG. Brolucizumab: a newly developed anti-VEGF molecule for the treatment of neovascular age-related macular degeneration. Ophthalmologica 2021;244:93-101.

Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020;127:72-84.

Holz FG, Dugel PU, Weissgerber G, et al. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology 2016;123:1080-9.

Tietz J, Spohn G, Schmid G, et al. Affinity and potency of RTH258 (ESBA1008), a novel inhibitor of vascular endothelial growth factor A for the treatment of retinal disorders. Invest Ophthalmol Vis Sci 2015;56:1501.

Gaudreault J, Gunde T, Floyd HS, et al. Preclinical pharmacology and safety of ESBA1008, a single-chain antibody fragment, investigated as potential treatment for age related macular degeneration. Invest Ophthalmol Vis Sci 2012;53:3025.

Nimz EL, Van't Land CW, Yáñez JA, Chastain JE. Intraocular and systemic pharmacokinetics of brolucizumab (RTH258) in nonhuman primates. Invest Ophthalmol Vis Sci 2016;57:4996.

Brown DM, Emanuelli A, Bandello F, et al. KESTREL and KITE: 52-week results from two phase III pivotal trials of brolucizumab for diabetic macular edema. Am J Ophthalmol 2022;238:157-72.

Monés J, Srivastava SK, Jaffe GJ, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology 2021;128:1050-9.

Motevasseli T, Mohammadi S, Abdi F, Freeman WR. Side effects of brolucizumab. J Ophthalmic Vis Res 2021;16:670-5.

Baumal CR, Spaide RF, Vajzovic L, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology 2020;127:1345-59.

Witkin AJ, Hahn P, Murray TG, et al. Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis 2020;4:269-79.

Pearce I, Amoaku W, Bailey C, et al. The changing landscape for the management of patients with neovascular AMD: brolucizumab in clinical practice. Eye (Lond) 2022;36:1725-34.

Mukai R, Matsumoto H, Akiyama H. Risk factors for emerging intraocular inflammation after intravitreal brolucizumab injection for age-related macular degeneration. PLoS One 2021;16:e0259879.

Kilmartin DJ. Literature review and proposal of best practice for ophthalmologists: monitoring of patients following intravitreal brolucizumab therapy. Iran J Med Sci 2022.

Baumal CR, Bodaghi B, Singer M, et al. Expert opinion on management of intraocular inflammation, retinal vasculitis, and vascular occlusion after brolucizumab treatment. Ophthalmol Retina 2021;5:519-27.

Sahni J, Patel SS, Dugel PU, et al. Simultaneous inhibition of angiopoietin-2 and vascular endothelial growth factor-A with faricimab in diabetic macular edema: BOULEVARD phase 2 randomized trial. Ophthalmology 2019;126:1155-70.

Wykoff CC, Abreu F, Adamis AP, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 2022;399:741-55.




How to Cite

Wong HL, FUNG NSK, Kwok AKH. Brolucizumab and faricimab as new treatment options for diabetic macular edema: perspective. Hong Kong J Ophthalmol [Internet]. 2022Dec.29 [cited 2024Apr.13];26(2). Available from:




Most read articles by the same author(s)

1 2 > >>