A new treatment round-up for AMD and GA

Age-related macular degeneration (AMD) is one of the main causes of irreversible vision loss in older individuals, affecting approximately 20 million patients in the United States and 196 million worldwide.¹By 2040, 288 million individuals are predicted to have this condition. Traditionally, AMD has been divided into 2 forms: dry AMD (90% of patients) and wet AMD (10% of patients).² Early and intermediate stages of AMD include extracellular deposits (drusen) in the outer retina that lead to photoreceptor degeneration and loss of central vision.¹ As the condition progresses, geographic atrophy (GA) can occur with confluent areas of photoreceptor, retinal pigment epithelium, and choriocapillaris loss.¹ GA can lead to irreversible vision loss and has affected 1.5 million individuals in the United States.³ Exudative (wet) AMD occurs when neovascularization leaks, leading to intraretinal/subretinal fluid and/or hemorrhages.¹ Risk factors for AMD include older age, genetic factors, and environmental factors such as cigarette smoking.¹

Newer therapies for dry AMD

Pegcetacoplan (Syfovre)

Apellis Pharmaceuticals developed pegcetacoplan (Syfovre) for the treatment of GA, and the FDA approved the agent in February 2023 for therapeutic use in patients with GA.⁴ It was the first drug available for the treatment of atrophic dry AMD.²The drug’s mechanism of action includes targeting the complement cascade, a natural component of the immune system, specifically the complement protein C3 and its activation fragment C3b.²This complement cascade has been implicated in the development of dry AMD and GA.²

In single-use vials, 15 mL of pegcetacoplan is intended to be administered by intravitreal injection into the affected eye once every 25 to 60 days.²In trials, monthly or bimonthly administration of the drug slowed GA progression over 24 months, with the greatest effect seen in the final 6 months. Adverse reactions may include ocular discomfort, vitreous floaters, ocular inflammation, and increased IOP.²Unfortunately, a major risk factor of pegcetacoplan is retinal vasculitis, which has caused the distribution company to lose two-thirds of its value.³ Another important adverse effect is that pegcetacoplan doubled the risk of conversion to wet AMD in every-other-month injections in comparison with sham injections.²

Avacincaptad pegol (Izervay)

Avacincaptad pegol (Izervay; Astellas Pharma US, Inc) is the next medication to date approved for the treatment of GA.³ In a similar manner to pegcetacoplan, avacincaptad pegol inhibits complement protein–C5 cleavage to C5a and C5b.³ This prevents downstream formation of membrane attack complex (MAC) and also prevents the activation of pro-inflammatory cytokines.⁵ The dosage for avacincaptad pegol is 2 mg injected intravitreally in each affected eye once monthly for up to 12 months.⁵ Overall results showed that the medication significantly reduced GA total lesion growth at 12 and 18 months compared with sham.⁶ Adverse effects include intraocular inflammation, including uveitis, vasculitis, and endophthalmitis.⁶ A similar adverse effect to that of pegcetacoplan was observed: After 18 months of treatment in the GATHER1 trial (NCT02686658), macular neovascularization occurred in 12% of patients treated with the 2-mg avacincaptad pegol dose monthly, compared with 3.6% of those treated with the sham.⁶

Although promising, neither pegcetacoplan nor avacincaptad pegol has resulted in improved visual acuity (VA).³

Valeda

Valeda is a multiwavelength photobiomodulation device indicated as a therapy for dry AMD to improve VA in patients with best-corrected VA (BCVA) of 20/32 to 20/70.⁷ The Valeda Light Delivery System uses 3 light emitting diodes (LED) to generate 3 wavelengths of light: 590 nm (yellow light), 660 nm (red light), and 850 nm (near-infrared).⁷ This is utilized to stimulate retinal mitochondrial production by promoting ATP production.⁷ A treatment session of 5 minutes should be completed 9 times per eye over 3 to 5 weeks.⁷ This cycle should be repeated every 4 months for 24 months.⁷

In the randomized clinical study LIGHTSITE III (NCT04065490), investigators evaluated 100 patients aged 50 or older with dry AMD and BCVA of 20/32 to 20/100. The data showed a significant improvement in BCVA in patients treated with Valeda, and results were sustained for up to 24 months, leading to FDA approval of the device in November 2024 for LumiThera.⁷ Adverse effects in 2% of patients included vitreous detachment, eye pain, and photopsia.⁷ Repeat treatment may be more effective and should be considered in future studies.

Newer therapies for wet AMD

Neovascular AMD (nAMD) involves abnormal choroidal neovascularization leading to central vision loss. It is the leading cause of legal blindness in patients aged 65 or older.⁸ The standard of care for wet AMD is serial anti-VEGF injections.⁸These medications reduce leakage from blood vessels, decrease retinal swelling, reduce vision loss, and improve VA in patients with nAMD.⁹

Ranibizumab (Susvimo)

A newer implantable port delivery system for ranibizumab (Susvimo) has been developed, which is implanted directly into the eye and allows for refills at 6 months or longer. This is an alternative, lower-maintenance therapy to the traditional regimen of anti-VEGF therapy.⁸ The FDA approved the system in October 2021 for the management of nAMD in eyes with at least 2 prior anti-VEGF injections.¹⁰ The high concentration of ranibizumab (100 mg/mL) delivered through the implant is an added benefit.¹⁰ Another advantage of this therapy is that it overcomes barriers to frequent anti-VEGF therapy, such as the cost of transportation, patient anxiety over serial injections, and the caregiver costs and resources required to accompany patients to multiple appointments. In the early stages of the LADDER study, vitreous hemorrhage was a concern, which was subsequently improved through future modifications to the device and surgical procedure.¹⁰

Faricimab (Vabysmo)

A newer dual-action injection drug is faricimab (Vabysmo). It is currently FDA approved to block 2 types of vision loss in patients with wet AMD and is also indicated for the treatment of diabetic macular edema (DME).¹¹ This injection is both an veg-F inhibitor (traditional medication utilized for wet AMD), and also angiopoietin-2 (Ang-2) inhibitor.¹¹ Ang-2 has been shown in early AMD to cause pericyte dropout, which leads to leakage and inflammation.¹¹Inhibiting ang-2 may further stabilize blood vessels in the retina. The drug is administered in 6mg/0.05 mL single use vials, and dosed every 4 weeks x 4 doses, then 6mg on weeks 28 and 44.⁹ The FDA approved Genentech's prefilled syringe in 2024.¹²

Data from multiple studies have confirmed faricimab's efficacy in improving BCVA and reducing central subfield macular thickness in populations with nAMD (TENAYA [NCT03823287] and LUCERNE [NCT03823300]) and DME (YOSEMITE [NCT03622580] and RHINE [NCT03622593]).¹³ Dosing intervals were also studied, with faricimab showing strong durability: A dosing interval of 16 weeks resulted in more than 59% of patients achieving and maintaining visual and anatomical improvements.¹³ In another study, investigators determined that faricimab may help treat patients with wet AMD that was previously resistant to other therapeutic options.¹⁴

Adverse effects of this medication include endophthalmitis, retinal detachment, retinal vasculitis, cataract (15%) and conjunctival hemorrhage (8%).¹¹

References:

1. Fleckenstein M, Schmitz-Valckenberg S, Chakravarthy U. Age-related macular degeneration: a review. JAMA. 2024;331(2):1538-3598. doi:10.1001/jama.2023.26074

2. Pegcetacoplan (Syfovre) for geographic atrophy in age-related macular degeneration. Med Lett Drugs Ther. 2023;65(1673):49-50. doi:10.58347/tml.2023.1673a

3. Patel H, Simhachalam Kutikuppala LV, Sharma S, et al. Izervay versus Syfovre: Two rivals recently approved for management of geographic atrophy. Ann Afr Med. 2024;23(3):523–524. doi:10.4103/aam.aam_186_23

4. Mastellos DC, Lambris JD. Pegcetacoplan (Syfovre): targeting complement C3 in geographic atrophy. Trends Pharmacol Sci. 2024;24(12):1175-1176. doi:10.1016/j.tips.2024.10.001

5. Avacinated pegol (Izervay) for geographic atrotphy in age-related macular degeneration. Med Lett Drugs Ther. 2024; 66(1694): 15-16. doi: 10.58347/tml.2023.1673a.

6. Rush RB, Klein W, Rush SW, Reinauer R. One-year outcomes in subjects developing macular neovascularization while underoig avacincaptad pegol therapy for geographic atrophy. Clin Ophthalmol. 2025;19:111-118. doi:10.2147/OPTH.S498985

7. Valeda Light Delivery System for age-related macular degeneration. Med Lett Drugs Ther. 2025;67(1720):9-10. doi:10.58347/tml.2025.1720a

8. Pericak J, Chin EK, Almeida DRP. Early SUSVIMO in neovascular age-related macular degeneration: real world case report and clinical implications. Int Med Case Rep J. 2024;17:849-853. doi:10.2147/IMCRJ.S475284

9. Faricimab (Vabysmo) for age-related macular degeneration and diabetic macular edema. Med Lett Drugs Ther. 2022;64(1646):45-46.

10. Sharma A, Khanani AM, Parachuri N, Kumar N, Bandello F, Kuppermann BD. Port delivery system with ranibizumab (Susvimo) recall–what does it mean to the retina specialists. Int J Retina Vitreous. 2023;9(1):6. doi:10.1186/s40942-023-00446-z

11. The power 2 open their world. Vabysmo. Accessed December 5, 2025. https://www.vabysmo-hcp.com.

12. FDA approves Genetech’s Vabysmo prefilled syringe (PFS) for three leading causes of vision loss. News release. Genentech. July 5. 2024. Accessed December 5, 2025. https://www.businesswire.com/news/home/20240628009339/en/FDA-Approves-Genentechs-Vabysmo-Prefilled-Syringe-PFS-for-Three-Leading-Causes-of-Vision-Loss

13. Chaudhary V, Guymer R, Artignan A, Downey A, Singh RP. Real-world evidence for faricimab in neovascular age-related macular degeneration and diabetic macular edema: a scoping review. Ophthalmol Sci, 2025;5(4): 100744, doi: 10.1016/j.xops.2025.100744Treatment for nAMD, DME, & RVO. Accessed: https://www.vabysmo-hcp.com.

14. Warter A, Galang C, Heinke A, et al. Use of faricimab (Vabysmo) for highly treatment resistant CNV in wet age-related macular degeneration. Invest Ophthalmol Vis Sci. 2023;64(8):2212Valeda Light Delivery System for age-related macular degeneration. Med Lett Drugs Ther. 2025;67(1720):9-10. doi:10.58347/tml.2025.1720a