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Neovascular Age-Related Macular Degeneration: Updates on Current Treatment Paradigms and Future Directions


Age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over the age of 60 years. Neovascular AMD (nAMD) is characterized by the development of choroidal neovascularization and is the main cause of vision loss in AMD patients. Despite remarkable advances in the therapeutic paradigm for nAMD, a high treatment burden and suboptimal response to existing agents in some patients still exist. In this issue of Ophthalmology Rounds, we review the current evidence-based treatments for nAMD and explore the future directions for the management of this condition. 

Age-related macular degeneration (AMD) is among the most common causes of visual impairment and blindness in the older population across the developed world.¹⁻³ Our understanding of the pathophysiology of AMD continues to expand, and multimodal imaging has refined our diagnostic approach in this disease. Diagnostic imaging modalities have advanced considerably for both dry and wet (neovascular) AMD (nAMD) and are summarized in Part 1 of the update on AMD that appeared in a recent previous issue of Ophthalmology Rounds.⁴ The development of new pharmacologic agents has provided more options in the therapeutic paradigm of nAMD. In this review, we evaluate the current treatments and future directions for therapy in nAMD.

Current Treatments in nAMD

As described in Part 2 of the recent AMD update,⁵ photodynamic therapy and laser photo-coagulation were historically used in the treatment of nAMD. These treatments were aimed at stabilizing progression of disease and avoiding severe vision loss; however, they were unable to offer robust visual improvement to patients.  

The advent of anti-vascular endothelial growth factor (VEGF) agents revolutionized the care of patients with nAMD. Those who are treated with anti-VEGF agents often experience improvements in visual acuity and visual quality, as well as a reduction in metamorphopsia. Anti-VEGF agents became the standard of care for patients with nAMD and the ensuing utilization of these agents grew considerably, with a compound annual growth rate of 21.8% from 2012 to 2017 and a total of 49,784 Canadians receiving these medications in 2017.⁶ 

Ranibizumab, a humanized anti-VEGF-A recombinant Fab fragment, inhibits all active isoforms of VEGF-A. It was approved by the United States (US) Food and Drug Administration (FDA) and Health Canada for the treatment of nAMD based on the results of the landmark phase III MARINA and ANCHOR trials, in which once-monthly ranibizumab demonstrated significant improvement in vision compared to control (placebo and verteporfin, respectively).⁷⁻⁸ Aflibercept, a soluble fusion protein, inhibits VEGF-A, VEGF-B, and placental growth factor. The phase III VIEW-1 and VIEW-2 trials showed that intravitreal aflibercept administered either monthly or every 2 months after 3 initial monthly loading doses achieved similar efficacy and safety outcomes as monthly ranibizumab.⁹ Bevacizumab is a humanized monoclonal antibody that inhibits all isoforms of VEGF-A. Originally approved for metastatic colon cancer, bevacizumab is not approved by either the FDA or Health Canada for nAMD. However, its off-label use in patients with nAMD is widespread and its efficacy and safety have been supported in multiple prospective, randomized, controlled nAMD trials.¹⁰⁻¹⁴

Despite substantial visual and anatomic improvements seen with monthly administration of anti-VEGF agents, the treatment burden on patients and caregivers remains high with this treatment regimen. Most recipients of traditional anti-VEGF agents require frequent injections and follow-up appointments, which can predispose them to procedural risks, pain, and adversely affect compliance, quality of life, and productivity.¹⁵⁻¹⁸ Alternative treatment approaches have been developed for this reason, the most common of which are pro re nata (PRN) dosing and dosing with treat-and-extend (T&E) approaches. With a PRN approach, patients undergo a clinical examination each month, but they only receive anti-VEGF therapy in the case of decreased vision, active fluid, or hemorrhage. With a T&E regimen, patients are treated each visit; however, the interval between visits may be extended in the case of disease inactivity. Typical T&E regimens extend the treatment interval in a gradual manner by 2- or 4-week increments until a maximum interval of 12-16 weeks.¹⁹ Large, multicentre, randomized trials have evaluated differences in efficacy and safety between T&E approaches and monthly dosing, including the CANTREAT trial performed at centres across Canada.²⁰⁻²² PRN dosing may not be as proactive as T&E dosing, with the possibility of disease activity recurrence in patients treated with this regimen.²³⁻²⁴ A 2020 Cochrane review found a clinically insignificant difference in the change in best-corrected visual acuity (BCVA) associated with monthly vs. PRN (mean difference 1.7 Early Treatment Diabetic Retino-pathy Study letters; 95% confidence interval [CI] 0.6, 2.8) and T&E (-0.5 letters; 95% CI -4.2, 3.1).²⁴ 


Brolucizumab is a novel humanized single-chain antibody fragment that inhibits all forms of VEGF-A. This agent is notable for having a low molecular weight relative to other anti-VEGF molecules and a high concentration gradient between the vitreous and retina which may enhance retinal delivery of the medication.¹⁹ In the phase III HAWK and HARRIER trials, brolucizu-mab was noninferior to aflibercept with respect to change in BCVA from baseline, while significantly reducing central subfield thickness (CST) and macular fluid vs. afli-bercept.²⁵ Although the initial HAWK and HARRIER studies noted that adverse events (AEs) were generally similar between brolucizumab and aflibercept, the American Society of Retinal Specialists began to receive reports shortly after FDA approval of episodes of intraocular inflammation (IOI) and rare vision-threatening cases of retinal vasculitis and retinal vascular occlusion associated with brolucizumab administration.²⁶⁻²⁸ A post hoc analysis of the HAWK and HARRIER trials found that of 49 of 1088 brolucizumab-treated eyes in the trials had evidence of ≥1 episode of IOI.²⁹ The phase III MERLIN trial, which investigated brolucizumab 6 mg given q4w, was terminated prematurely further to the higher rate of IOI in the brolucizumab group (9.3%) vs. aflibercept (4.5%).³⁰ Novartis also terminated the RAPTOR and RAVEN trials examining brolucizumab in patients with branch and central retinal vein occlusion (RVO), respectively.³¹⁻³² Thus, although brolucizumab remains indicated by Health Canada for the treatment of nAMD and diabetic macular edema (DME), its use in clinical practice has been limited by these serious AE concerns. 

Emerging and Future Treatments in nAMD (Table 1)

Table 1. New approved and investigational innovative therapies in nAMD


ᵃApproved by Health Canada

Ang, angiopoietin; BCVA, best-corrected visual acuity; CRT, central retinal thickness; CST, central subfield thickness; nAMD, neovascular age-related macular degeneration; q12w, every 12 weeks; VEGF, vascular endothelial growth factor


Faricimab is a novel bispecific antibody that binds both VEGF-A and angiopoietin-2 (Ang-2) with high specificity and affinity. Ang-2 is involved in the inflammatory cascade of AMD and promotes angiogenesis alongside VEGF.³³ In the landmark phase III TENAYA and LUCERNE trials, treatment-naïve patients with nAMD were randomized to faricimab 6.0 mg extended up to q16w based on disease activity criteria or aflibercept 2.0 mg q8w.³⁴ The mean change in BCVA in the faricimab group from baseline averaged over weeks 40, 44, and 48 was found to be noninferior to the aflibercept group (TENAYA: +5.8 letters with faricimab, +5.1 letters with aflibercept; LUCERNE: +6.6 letters with faricimab, +6.6 letters with aflibercept). The adjusted mean change in CST at 48 weeks was also determined to be noninferior with faricimab up to q16w vs. aflibercept. At week 48, 45.7% and 44.9% of patients receiving faricimab in TENAYA and LUCERNE, respectively, had attained q16w dosing and 34.0% and 32.9%, respectively, had attained q12w dosing. Ocular AEs were comparable between the faricimab and aflibercept treatment arms in both trials. Overall, faricimab demonstrated high efficacy for nAMD with interval extension of up to q16w between treatments. Based on these outcomes, faricimab was approved by Health Canada in May 2022 for nAMD, as well as for DME based on the results of the phase III YOSEMITE and RHINE trials.³⁵ The ongoing investigator-driven, real-world, multicentre, prospective TRUCKEE study is evaluating the efficacy, durability, and safety of faricimab in nAMD patients who have received faricimab since FDA approval.³⁶

Ranibizumab port delivery system (PDS)

The objective of the ranibizumab PDS is to provide sustained intravitreal anti-VEGF therapy via an implantable device.¹⁹ The PDS is slightly longer than a grain of rice and is implanted via a scleral incision in the pars plana. The ranibizumab PDS was evaluated in the phase III, open-label Archway trial, in which patients with nAMD were randomized to ranibizumab PDS with a fixed 24-week refill-exchange procedure or intravitreal ranibizumab 0.5 mg q4w.³⁷ Ranibizumab PDS was found to be noninferior to monthly ranibizumab, with a comparable adjusted mean change in BCVA from baseline averaged over weeks 36 and 40 (+0.2 letters in the PDS cohort, +0.5 letters in the monthly ranibizumab arm). Supplemental ranibizumab before the first refill-exchange procedure was not required in 98.4% of patients with the ranibizumab PDS. Ocular AEs of interest to PDS were higher in the ranibizumab PDS arm (19.0%) compared to monthly ranibizumab (6.0%), including endophthalmitis (1.6% of PDS cases), retinal detachment (0.8%), vitreous hemorrhage (5.2%), conjunctival erosions (2.4%), and conjunctival retraction (2.0%). Ranibizumab PDS was approved by Health Canada in September 2022. 


High-dose aflibercept  

High-dose (8 mg) aflibercept has been investigated as a way of improving treatment durability compared to standard therapy while maintaining VA gains. The international, multicentre, phase II/III PULSAR trial assessed the efficacy, durability, and safety of aflibercept 8 mg intravitreal injections for the management of nAMD.³⁸ The q12w and q16w regimens were found to be noninferior to aflibercept 2 mg q8w with respect to mean change in BCVA at 48 weeks (+6.7, +6.2, and +7.6 letters, respectively). Central retinal thickness was likewise noninferior with high-dose aflibercept q12w and q16w vs. 2 mg q8w. The q12w and q16w dosing intervals were maintained in 79% and 77% of patients, respectively. The safety profile of aflibercept 8 mg was consistent with that of standard aflibercept 2 mg. Based on these data, the FDA accepted high-dose aflibercept for priority review.³⁹   

Tarcocimab tedromer (KSI-301)

KSI-301 is an investigational anti-VEGF antibody biopolymer conjugate that blocks all isoforms of VEGF-A and is currently being studied for the treatment of patients with nAMD.⁴⁰⁻⁴¹ The size (950 kDa) and molar dose of KSI-301 are designed to provide optimal intra-ocular durability. A phase Ia study of KSI-301 in 9 patients with DME found that rapid improvements in BCVA and OCT parameters were maintained at 12 weeks after a single dose, and no drug-related AEs or dose-limiting toxicities were observed.⁴² A phase Ib, open-label, randomized study was then conducted in 121 treatment-naïve patients with nAMD, DME, and RVO to evaluate 2.5 mg or 5 mg of KSI-301, administered as 3 monthly loading doses followed by monthly evaluation and retreatment based on specific criteria.⁴³ The first retreatment was at ≥4 months in 82% (40 of 49) and at 6 months in 49% (20 of 41) of patients with nAMD. Overall, 29 serious AEs were observed across 546 injections, and none were deemed to be drug related; both of the reported cases of IOI resolved completely. The prospective, multicentre, randomized, phase II/III DAZZLE study compared KSI-301 5 mg at 3 treatment intervals – q12w, q16w, and q20w – to aflibercept in 557 patients with nAMD.⁴⁴ DAZZLE was terminated in 2022 because the primary endpoint of least-square means change from baseline in BCVA at an average of 48 and 52 weeks was not met (KSI-301: 1.0 [95% CI -0.5, 2.5]; aflibercept 7.0 [5.5, 8.5]); however, mean gains in BCVA among the 59.4% of patients in the KSI-301 group who achieved q20w dosing were noninferior to those in the aflibercept group. KSI-301 was well tolerated; ocular AEs occurred in 45.8% and 36.4% of KSI-301- and aflibercept-treated patients, and 6 KSI-301 patients experienced a serious AE vs. none in the aflibercept group. Phase III trials in DME and macular edema secondary to RVO are ongoing. 

Abicipar pegol

Abicipar pegol is a designed ankyrin repeat protein whose characteristics are different from traditional antibodies. Abicipar has high specificity to all soluble isoforms of VEGF-A, a long ocular half-life, a pegylated molecular structure, and a high affinity for target binding.⁴⁵ Pooled data from the phase III SEQUOIA and CEDAR trials found that abicipar 2 mg q8w and q12w improved BCVA from baseline to week 104 by 7.8 and 6.1 letters, respectively, compared with 8.5 letters with ranibizumab q4w (control).⁴⁶ VA was stable (<15-letter loss) to 104 weeks in 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498) of patients in the abicipar q8w, abicipar q12w, and ranibizumab groups, respectively. The mean changes in CRT were equivalent between groups (-147 µm, -146 µm, and -142 µm, respectively). IOI was detected in a higher proportion of eyes treated with abicipar (16.2% for q8w and 17.6% for q12w) than in the ranibizumab group (1.3%) by week 104. While these studies showed that abicipar q8-12w had similar visual and anatomic outcomes to monthly ranibizumab at 2 years, the FDA did not approve abicipar for clinical use, citing an unfavourable risk-benefit ratio with respect to the higher risk of IOI events.⁴⁷ Allergan subsequently withdrew similar applications to regulatory bodies in both Europe and Japan. 

Biosimilars (Table 2)

Table 2. Approved and investigational biosimilar anti-VEGFs for the treatment of nAMD

The World Health Organization defines biosimilars as biological products that are shown to be highly similar in terms of their quality, safety, and efficacy to already licensed reference products.⁴⁸ The advent of biosimilar medications in the US is predicted to reduce drug costs by $100 billion over the next 5 years.⁴⁹ As of February 2023, 52 biosimilar agents have been approved by Health Canada.⁵⁰ Ten of the 13 provinces and territories have implemented mandatory biosimilar switching policies.⁵¹ 

Further to recent patent expirations of Lucentis® (ranibizumab) and Eylea® (aflibercept), biosimilar anti-VEGF medications for these agents have been developed.¹⁹ The first of these agents to be approved by Health Canada is SB11 (Byooviz™; ranibizumab-nuna).⁵² In a randomized, parallel-group equivalence study, 705 patients with nAMD were randomized to either ranibizumab or SB11 (0.5 mg q4w for each agent) and were followed for 48  weeks.⁵³ At the preplanned 24-week interim analysis, SB11 demonstrated equivalent efficacy to ranibizumab, with comparable least-squares mean changes from baseline to week 8 in BCVA (primary endpoint) (SB11: +6.2 letters; ranibizumab: +7.0 letters; adjusted difference -0.8 letters; 90% [CI] -1.8, 0.2 letters) and to week 4 in CST (SB11: -108 µm; ranibizumab: -100 µm; adjusted treatment difference -8 µm (95% CI -19, 3 µm). Ocular adverse events, serious adverse events, and immunogenicity profiles were also similar between these 2 agents. The equivalence of efficacy and safety were maintained when patients were followed until 52 weeks.⁵⁴ In a post hoc analysis of the same randomized trial, the serum antidrug antibodies as a marker of immunogenicity of both SB11 and ranibizumab were analyzed, and no association was found between these antibodies and efficacy or safety parameters in both the SB11 and ranibizumab groups.⁵⁵ As a cost comparison, the current list price of Byooviz in the US is $1,130 for a single-use 0.5-mg vial, which is ~40% lower than the $1,850 list price of Lucentis.⁵⁶ It should be noted that the same price differential may not be applicable in Canadian provinces and territories.

Other ranibizumab biosimilars are in various stages of development and regulatory approval. FYB201 (ranibizumab-eqrn) was approved by the FDA in August 2022. The randomized, evaluation-masked, parallel-group phase III COLUMBUS-AMD study investigated the clinical equivalence of FYB201 to reference ranibizumab (0.5 mg q4w for both agents) in 477 patients with nAMD over 48 weeks.⁵⁷ The mean BCVA improvement at 8 weeks (primary endpoint) of +5.1 letters in the FYB201 group and +5.6 letters in the ranibizumab cohort, and the 90% CI of -1.6 to 0.9 was within the predefined equivalence margin. Adverse events and immunogenicity profiles were comparable between the 2 treatment groups. The cost of Cimerli™ in the US is $1,360 for a 0.5-mg vial, which is 26% lower than Lucentis.⁵⁶ Phase III studies of other biosimilar ranibizumab agents have been completed (CKD-701, SJP-0133/GBS-007, Xlucane™) or are ongoing (LUBT010).⁵⁸  

Several aflibercept biosimilars are in phase III trials. Phase III study data showed that patients with nAMD who received SB15 experienced equivalent changes from baseline to week 32 in BCVA and CST to those receiving reference aflibercept.⁵⁹ No new safety signals were identified and the adverse event profile was similar to reference aflibercept. 

Three biosimilars of bevacizumab – Mvasi® (bevacizumab-awwb), Zirabev™ (bevacizumab-bvzr), and Almysys® (bevacizumab-maly) – have been approved by the FDA for the management of various types of cancer.⁶⁰⁻⁶² There are no robust data supporting the use of these biosimilars in nAMD, and the American Academy of Ophthalmology has expressed concern that these agents will be considered by payers to be biosimilar to compounded bevacizumab in this patient population.⁶³ It also remains unclear whether compounding pharmacies will repackage bevacizumab biosimilars for intra-vitreal administration.⁶⁴ 


Anti-VEGF treatments have saved the sight of millions of patients with nAMD; however, the treatment burdens on patients, caregivers, and the healthcare system remain high. New and emerging agents aim to reduce this burden on patients by increasing the injection interval while maintaining the safety of these agents. In 2023, we are likely in the beginning of a paradigm shift with the introduction of effective and safe biosimilar anti-VEGF agents which aim to reduce the healthcare cost of treating nAMD and make anti-VEGF therapy accessible to more patients. It is important that ophthalmologists continue to practice evidence-based medicine and make decisions that optimize patient outcomes, as well as serve as stewards of healthcare resources.


  1. Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122(4):564-572. 

  2. Li JQ, Welchowski T, Schmid M, Mauschitz MM, Holz FG, Finger RP. Prevalence and incidence of age-related macular degeneration in Europe: a systematic review and meta-analysis. Br J Ophthalmol. 2020;104(8):1077-1084. 

  3. Maberley DAL, Hollands H, Chuo J, et al. The prevalence of low vision and blindness in Canada. Eye. 2006;20(3):341-346.

  4. Tri Ta Kim D, Berger AR. Update on age-related macular degeneration – Part 1: current and future trends in diagnosis. Ophthalmology Rounds. 2020;14(1):1-6. Available at:

  5. Tri Ta Kim D, Berger AR. Update on age-related macular degeneration – Part 2: current and future treatment strategies. Ophthalmology Rounds. 2020;14(2):1-6.

  6. Patented Medicine Prices Review Board. Market intelligence report: anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal conditions, 2017. Government of Canada; 2018. Accessed March 12, 2023. 

  7. Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-1431.

  8. Brown DM, Michels M, Kaiser PK, et al; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009;116(1):57-65.e5.

  9. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548.

  10. CATT Research Group; Martin DF, Maguire MG, Ying G-S, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897-1908. 

  11. Chakravarthy U, Harding SP, Rogers CA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet. 2013;382(9900):1258-1267. 

  12. Kodjikian L, Souied EH, Mimoun G, et al. Ranibizumab versus bevacizumab for neovascular age-related macular degeneration: results from the GEFAL noninferiority randomized trial. Ophthalmology. 2013;120(11): 2300-2309. 

  13. Krebs I, Schmetterer L, Boltz A, et al. A randomised double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration. Br J Ophthalmol. 2013;97(3):266-271. 

  14. Schauwvlieghe A-SME, Dijkman G, Hooymans JMM, Verbraak FD, Dijkgraaf MG, Peto T, et al. Comparing the effectiveness of bevacizumab to ranibizumab in patients with exudative age-related macular degeneration: the BRAMD Study. PLoS One. 2016;11(5):e0153052.

  15. Rosenberg D, Deonarain DM, Gould J, et al. Efficacy, safety, and treatment burden of treat-and-extend versus alternative anti-VEGF regiments for nAMD: a systematic review and meta-analysis. Eye. 2023;37(1):6-16. 

  16. Pina Marín B, Gajate Paniagua NM, Gómez-Baldó L, Gallego-Pinazo R. Burden of disease assessment in patients with neovascular age-related macular degeneration in Spain: Results of the AMD-MANAGE study. Eur J Ophthalmol. 2022;32(1):385-394.

  17. Spooner KL, Mhlanga CT, Hong TH, Broadhead GK, Chang AA. The burden of neovascular age-related macular degeneration: a patient’s perspective. Clin Ophthalmol. 2018;12:2483-2491.

  18. Giocanti-Aurégan A, García-Layana A, Peto T, et al. Drivers of and barriers to adherence to neovascular age-related macular degeneration and diabetic macular edema treatment management plans: a multi-national qualitative study. Patient Prefer Adherence. 2022;16:587-604.

  19. Holekamp NM. Review of neovascular age-related macular degeneration treatment options. Am J Manag Care. 2019;25:S172-S181. 

  20. Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a treat-and-extend regimen with ranibizumab in patients with neovascular age-related macular disease: a randomized clinical trial. JAMA Ophthalmol. 2020;138(3):244-250.

  21. Silva R, Berta A, Larsen M, et al. Treat-and-extend versus monthly regimen in neovascular age-related macular degeneration: results with ranibizumab from the TREND study. Ophthalmology. 2018;125(1):57-65.

  22. Wykoff CC, Croft DE, Brown DM, et al. Prospective trial of treat-and-extend versus monthly dosing for neovascular age-related macular degeneration: TREX-AMD 1-year results. Ophthalmology. 2015;122(12):2514-22. 

  23. Freund KB, Korobelnik JF, Devenyi R, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases: a literature review and consensus recommendations. Retina. 2015;35(8):1489-1506. 

  24. Li E, Donati S, Lindsley KB, et al. Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020;5(5):CD012208. 

  25. 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(1):72-84. 

  26. American Society of Retina Specialists. Beovu Update for ASRS Members. February 23, 2020. 

  27. Baumal CR, Spaide RF, Vajzovic L, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology. 2020;127(10):1345-59. 

  28. Sharma A, Kumar N, Parachuri N, et al. Brolucizumab – termination of 4 weekly trials – rebalancing the immunogenicity risk. Exp Opin Biol Ther. 2022;22(4):441-3. 

  29. Singer M, Albini TA, Seres A et al.Clinical characteristics and outcomes of eyes with intraocular inflammation after brolucizumab: post hoc analysis of HAWK and HARRIER. Ophthalmology Retina. 2022;6(2):97-108. 

  30. Khanani AM, Brown DM, Jaffe GJ, et al. MERLIN: Phase 3a, multicenter, randomized, double-masked trial of brolucizumab in participants with neovascular age-related macular degeneration and persistent retinal fluid. Ophthalmology. 2022;129(9):974-85. 

  31. Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion (RAPTOR). Available at: Accessed on April 6, 2023. 

  32. Assessing the efficacy and safety of brolucizumab versus aflibercept in patients with visual impairment due to macular edema secondary to central retinal vein occlusion (RAVEN). Available at: Accessed on April 6, 2023.

  33. Chakravarthy U, Bailey C, Brown D, et al. Phase I trial of anti-vascular endothelial growth factor/anti-angiopoietin 2 bispecific antibody RG7716 for neovascular age-related macular degeneration. Ophthalmology Retina. 2017;1(6):474-485.

  34. Heier JS, Khanani AM, Ruiz CQ, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet. 2022;399(10326):729-740. 

  35. Wykoff CC, Abreu F, Adamis AP, et al; YOSEMITE and RHINE Investigators. 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(10326):741-755.

  36. Khan H, Aziz AA, Abbey AM, et al. Real world efficacy, durability and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study. EURetina 2023 Conference, Hamburg, Germany. Available at: Accessed on April 6, 2023. 

  37. Holekamp NM, Campochiaro PA, Chang MA, et al. Archway randomized phase 3 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology. 2022;129(3):295-307. 

  38. Lanzetta P. Intravitreal aflibercept injection 8 mg for nAMD: 48-week results from the Phase 3 PULSAR trial. Presented at the American Academy of Ophthalmology Annual Meeting. September 30-October 3, 2022: Chicago (IL). 

  39. Callanan D, Kunimoto D, Maturi RK, et al; REACH Study Group. Double-masked, randomized, phase 2 evaluation of abicipar pegol (an anti-VEGF DARPin therapeutic) in neovascular age-related macular degeneration. J Ocul Pharmacol Ther. 2018;34(10):700-709. 

  40. Liang H, Huang X, Ngo W, et al. KSI-301: an anti-VEGF antibody biopolymer conjugate with extended half-life for treatment of neovascular retinal diseases. Invest Ophthalmol Vis Sci. 2018;59:211.  

  41. Dugel PU. Extended durability in exudative retinal diseases using a new class of molecules: novel anti-VEGF antibody biopolymer conjugate KSI-301. Presented at the EURetina 2019 Congress. September 8, 2019. Paris (France).  

  42. Patel SS, Naor J, Qudrat A, et al. Phase 1 first in-human study of KSI-301: a novel anti-VEGF antibody biopolymer conjugate with ex tended durability. Invest Ophthalmol Vis Sci. 2019;60:3670.

  43. Do DV. Extended durability in exudative retinal diseases using the novel intravitreal anti-VEGF antibody biopolymer conjugate KSI-301: update from phase 1b study in patients with wAMD, DME and RVO. In: Angiogenesis, Exudation and Degeneration, 8 February 2020. KODIAK Sciences,

  44. Regillo C. Efficacy, durability and safety of KSI-301 antibody biopolymer conjugate in wet AMD: primary results of the Phase 2b/3 DAZZLE study. Presented at the 2022 Annual Meeting of the Association for Research in Vision and Ophthalmology. May 1-5, 2022: Denver (CO). 

  45. Hutton D. FDA accepts aflibercept 8 mg BLA for treatment of wet AMD and DME for priority review. Ophthalmology Times. February 23, 2023. Available at: Accessed on April 10, 2023. 

  46. Khurana RN, Kunimoto D, Yoon YH, et al. Two-year results of the phase 3 randomized controlled study of abicipar in neovascular age-related macular degeneration. Ophthalmology. 2021;128(7):1027-38. 

  47. Mullard A. News in brief: FDA rejects first DARPin. July 7, 2020. Available at: Accessed on April 6, 2023. 

  48. World Health Organization. Guidelines on evaluation of biosimilars: replacement of Annex 2 of WHO Technical Report Series, No. 977. 2022. Available at: Accessed on April 12, 2023. 

  49. IQVIA Institute for Human Data Science. Biosimilars in the United States 2020–2024 Competition, Savings, and Sustainability Institute Report, Sep 29, 2020. Available at: Accessed September 2021.

  50. Generics and Biosimilars Initiative. Biosimilars approved in Canada. February 17, 2023. Available at:,in%20Canada%2C%20see%20Table%201. Accessed on April 12, 2023.

  51. Joszt L, More Canadian jurisdictions implement mandatory biosimilar switching policies. Am J Manag Care. April 1, 2023. Available at: Accessed on April 13, 2023. 

  52. Biogen Canada Inc. BYOOVIZ™ (ranibizumab injection) Product Monograph. Date of authorization: March 8, 2022. 

  53. Woo SJ, Veith M, Hamouz J, et al. Efficacy and safety of a proposed ranibizumab biosimilar product vs a reference ranibizumab product for patients with neovascular age-related macular degeneration: a randomized clinical trial. JAMA Ophthalmol. 2021;139(1):68-76. 

  54. Bressler NM, Veith M, Hamouz J, et al. Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes. Br J Ophthalmol. 2023;107(3):384-391. 

  55. Bressler NM, Kim T, Oh I, et al. Immunogenicity with ranibizumab biosimilar SB11 (Byooviz) and reference product lucentis and association with efficacy, safety, and pharmacokinetics: a post hoc analysis of a phase 3 randomized clinical trial. JAMA Ophthalmol. 2023;141(2):117-27. 

  56. Sharma A, Wu L, Bloom S, et al. Biosimilar biologics – need for real world data; autologous choroidal transplantation for wet AMD. Ophthalmic SUrg Lasers Imaging Retina. 2022;53(11):602-605.

  57. Holz FG, Oleksy P, Ricci F, et al. Efficacy and safety of biosimilar FYB201 compared with ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2022;129(1):54-63. 

  58. Kapur M, Nirula S, Naik MP. Future of anti-VEGF: biosimilars and biobetters. Int J Retina Vitreous. 2022;8:2. 

  59. Woo SJ, Sadda SR, Bradvica M, et al. SB15, a Proposed Biosimilar to Aflibercept, in nAMD: 32-Week Results. Presented at the American Academy of Ophthalmology (AAO) 2022 Annual Meeting. September 30 – October 3, 2022: Chicago (IL). Poster PO381.

  60. Amgen and Allergan. MVASI® (bevacizumab-awwb) Prescribing Information. Revised September 2017. 

  61. Pfizer Inc. ZIRABEV™ (bevacizumab-bvzr) Prescribing Information. Revised June 2019. 

  62. Amneal Pharmaceuticals LLC. ALMYSYS® (bevacizumab-maly) Prescribing Information. Revised April 2022. 

  63. Hagen T. An interview with the AAO about its bevacizumab concerns. Am J Manag Care. August 10, 2021. Available at: Accessed on April 13, 2023. 

  64. Baumal CR. Wet age-related macular degeneration: treatment advances to reduce injection burden. Am J Manage Care. 2020;26(5):S103-S111. 

Dr. Popovic is a resident physician in the Department of Ophthalmology and Vision Sciences at the University of Toronto. Dr. Christakis is a retinal specialist at the Kensington Eye Institute and at the Toronto Western Hospital, and he is an Assistant Professor in the Department of Ophthalmology and Vision Sciences at the University of Toronto.

Financial Disclosures: Dr. Popovic declared institutional financial support from the PSI Foundation and Fighting Blindness Canada. Dr. Christakis stated that he has no disclosures to report in association with the contents of this issue.

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© 2023 Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto, which is solely responsible for the contents. Publisher: Snell Medical Communication Inc. in cooperation with the Department of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Toronto. ®Ophthalmology Rounds is a registered trademark of Snell Medical Communication Inc. All rights reserved. The administration of any therapies discussed or referred to in Ophthalmology Rounds should always be consistent with the approved prescribing information in Canada. Snell Medical Communication Inc. is committed to the development of superior Continuing Medical Education.

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