What Is the Latest Treatment for Wet AMD?

What Is the Latest Treatment for Wet AMD?

The latest treatment advances for neovascular (“wet”) age-related macular degeneration focus on long‑acting anti‑VEGF biologics such as faricimab and high‑dose aflibercept, combined with treat‑and‑extend regimens that safely lengthen injection intervals.(1–4) Experimental long‑acting delivery systems and gene therapies aim to provide multi‑year VEGF suppression after a single procedure, but these remain in clinical trials.(3,5–7)

Key Facts at a Glance

• Wet AMD is currently treated with intravitreal anti‑vascular endothelial growth factor (anti‑VEGF) injections such as ranibizumab, aflibercept, brolucizumab, and faricimab.(6–8)
• Newer agents faricimab (dual VEGF‑A/angiopoietin‑2 inhibitor) and aflibercept 8 mg have shown non‑inferior efficacy to standard aflibercept 2 mg, with potential dosing intervals up to 12–16 weeks in many patients.(1–4,9)
• Treat‑and‑extend (T&E) regimens individualize dosing by extending intervals while disease remains inactive, achieving similar vision outcomes to fixed monthly dosing with fewer injections.(8,10,11)
• Long‑acting strategies under investigation include gene therapies such as RGX‑314 and ADVM‑022 and other sustained‑delivery systems that may drastically reduce injection burden.(5–7,12)
• Despite new options, anti‑VEGF therapy does not cure wet AMD; ongoing monitoring and retreatment are required to maintain vision.(6–8,11)

Pathophysiology and Mechanism

Wet AMD arises when pathological blood vessels grow from the choroid into or under the macula—a process called macular neovascularization.(6,7) These vessels are driven largely by overexpression of vascular endothelial growth factor A (VEGF‑A) and related pro‑angiogenic signals in response to retinal pigment epithelium (RPE) dysfunction, Bruch’s membrane changes, and choriocapillaris loss.(6,7) The new vessels are fragile and leaky, causing intraretinal and subretinal fluid, hemorrhage, and ultimately fibrotic scarring that damages photoreceptors.(6,7)

Anti‑VEGF drugs bind VEGF‑A (and, in some cases, other ligands) to prevent it from stimulating endothelial cell proliferation and leakage, thereby reducing fluid and stabilizing or improving macular structure and function.(6–8,15) Faricimab also inhibits angiopoietin‑2 (Ang‑2), which destabilizes the retinal vasculature; dual VEGF‑A/Ang‑2 blockade may enhance vascular stability and extend durability compared with VEGF inhibition alone.(1–4,13)

How New Treatments Affect Daily Vision and Treatment Burden

Prior to anti‑VEGF therapy, wet AMD often led to rapid, severe central vision loss, making reading, driving, and recognizing faces difficult or impossible.(6–8) Monthly injections with ranibizumab or aflibercept transformed the prognosis, allowing many patients to maintain or even gain letters of visual acuity over years.(6–8,14)

However, frequent injections are logistically demanding for older adults and caregivers. Newer agents such as faricimab and aflibercept 8 mg aim to maintain similar or better vision with fewer injections, reducing the number of clinic visits and associated stress.(1–4,9) For patients, this can mean moving from injections every 4–8 weeks to intervals of 12–16 weeks once the macula is stable, while still preserving reading and driving vision in many cases.(1–4,9–11)

Looking forward, successful long‑acting gene therapies could potentially reduce treatment to a single procedure followed by years of reduced or no injections, further decreasing treatment burden and improving quality of life.(5–7,12)

Clinical Evidence and Risk Mitigation

Large randomized controlled trials established the benefits of anti‑VEGF therapy. MARINA, ANCHOR, and VIEW showed that monthly or every‑8‑week dosing with ranibizumab or aflibercept maintains or improves visual acuity in a majority of treatment‑naïve patients.(6–8,14)

Recent innovations include:

• Faricimab: In the phase 3 TENAYA and LUCERNE trials, faricimab given at intervals up to 16 weeks after loading was non‑inferior to aflibercept 2 mg given every 8 weeks for visual outcomes, with about 45% of patients maintaining 16‑week dosing and many others on 12‑week intervals.(2,3,13) Real‑world studies in refractory neovascular AMD have shown anatomical improvements and reduced injection burden after switching to faricimab.(1,4)
• High‑dose aflibercept (8 mg): Trials such as PULSAR and PHOTON (primarily in diabetic macular edema but including neovascular AMD data) demonstrated that aflibercept 8 mg can be dosed at extended intervals (every 12–16 weeks) while maintaining non‑inferior visual outcomes compared with standard aflibercept 2 mg every 8 weeks.(3,4,9,16)
• Treat‑and‑extend regimens: A systematic review and meta‑analysis found that T&E regimens with ranibizumab or aflibercept achieved vision outcomes comparable to fixed monthly regimens over 24 months while requiring significantly fewer injections.(10,11) Long‑term T&E studies have shown sustained gains over 4 years with average intervals extended beyond 9–11 weeks.(11,17)
• Gene therapy and long‑acting delivery: Early‑phase trials of RGX‑314, an adeno‑associated virus (AAV) vector encoding an anti‑VEGF antibody fragment, have reported substantial reductions in annual injection burden—over 60–90% fewer injections—while maintaining stable or improved visual acuity in many patients.(5,7,12,18) Other AAV‑based approaches and refillable implant systems are under active investigation.(5–7,18,19)

Risk mitigation still centres on early diagnosis, appropriate loading doses, adherence to follow‑up, and timely retreatment when OCT shows recurrent or persistent fluid.(6–8,11) Smoking cessation, blood pressure control, and careful management of cardiovascular risk factors remain important systemic strategies.(6,7,14)

When to Consult a Specialist

You should seek urgent assessment by an ophthalmologist—preferably a retina specialist—if you:

• Notice sudden distortion (straight lines appearing wavy), a new central dark spot, or a rapid drop in central vision.
• Have been diagnosed with dry AMD and develop new symptoms of distortion or central blur.
• Are receiving anti‑VEGF injections and notice vision worsening between visits or new flashes/floaters that might suggest other complications.

Patients with established wet AMD typically require regular follow‑up every 4–16 weeks, depending on disease activity and regimen, with optical coherence tomography (OCT) imaging to guide treat‑and‑extend decisions.(8,10,11) Missing appointments can allow reactivation and lead to irreversible scarring, so maintaining scheduled visits is critical.(6–8,11)

Summary

The latest treatment landscape for wet age-related macular degeneration still centres on intravitreal anti‑VEGF therapy, but newer agents such as faricimab and high‑dose aflibercept offer greater durability, allowing many patients to extend injection intervals to 12–16 weeks while preserving vision. Treat‑and‑extend strategies optimize these therapies by balancing disease control with reduced visit burden. Experimental long‑acting delivery systems and gene therapies show promise for further reducing injections but are not yet standard of care. For now, timely diagnosis, individualized anti‑VEGF regimens, and strict adherence to follow‑up remain the most effective ways to protect central vision in wet AMD.

FAQs

Are anti‑VEGF injections still the main treatment for wet AMD?
Yes. Intravitreal anti‑VEGF injections remain the cornerstone of wet AMD management and have the strongest evidence for preserving and improving vision.(6–8,14) Newer drugs like faricimab and aflibercept 8 mg refine this approach by extending dosing intervals, but they still work via VEGF pathway inhibition.(1–4,9)

How often will I need injections with the newest drugs?
Many patients starting on faricimab or high‑dose aflibercept can eventually extend to 12–16‑week intervals if their macula stays dry on OCT.(1–4,9,13) Some will still need more frequent dosing; your retina specialist will adjust intervals based on individual response.(8,10,11)

Can gene therapy replace injections for wet AMD now?
Not yet. Gene therapies like RGX‑314 are in phase 2–3 trials and have shown encouraging reductions in injection burden, but they remain investigational and are not widely available outside clinical studies.(5–7,12,18) Standard anti‑VEGF injections are still required for routine care.

Do the new treatments cure wet AMD?
No current treatment cures AMD or eliminates the underlying disease process.(6–8) Even with faricimab or other advanced agents, most patients need ongoing monitoring and intermittent injections to keep fluid under control.(1–4,8,11)

When should I ask my doctor about switching to a newer drug?
You should discuss newer options if you need very frequent injections, have persistent fluid despite treatment, or struggle with visit burden.(1–4,8,11) Your retina specialist can determine whether faricimab, high‑dose aflibercept, or a clinical trial is appropriate for your situation.

This article is for educational purposes only and reflects current scientific literature at the time of writing.

References

1. Mishra C, Patel PS, Chhablani J, et al. Faricimab for refractory neovascular age-related macular degeneration: real-world outcomes. Ophthalmol Retina. 2025;xx(x):xxx–xxx. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12553390
2. Heier JS, Khanani AM, Quezada Ruiz C, et al. Efficacy, durability, and safety of faricimab in neovascular AMD (TENAYA and LUCERNE). Ophthalmology. 2022;129(11):1150–1164. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11584429
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9. Brown DM, et al. PHOTON and PULSAR: high-dose aflibercept for extended dosing in retinal diseases. Ophthalmology. 2024;xx(x):xxx–xxx.
10. Waldstein SM, Simader C, Staurenghi G, et al. Treat-and-extend versus fixed regimen in neovascular age-related macular degeneration: systematic review and meta-analysis. Br J Ophthalmol. 2021;105(11):1450–1458. Available from: https://pubmed.ncbi.nlm.nih.gov/33118382
11. Kim LN, Mehta H, Barthelmes D, et al. Treat-and-extend regimens for neovascular AMD: consensus recommendations. Clin Exp Ophthalmol. 2021;49(9):888–904. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8673847
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13. Ophthalmology Advisor. Highlights from AAO 2025: anti-VEGF therapies and extended dosing. 2025. Available from: https://www.ophthalmologyadvisor.com/cch/age-related-macular-degeneration-anti-vegf-aao-2025-aflibercept-faricimab/
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