Exudative (Wet) Age-Related Macular Degeneration (AMD) Medication

Updated: Jun 16, 2022
  • Author: F Ryan Prall, MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Medication Summary

As of February 2023, the most recent approval is pegcetacoplan intravitreal (Syfovre), a complement inhibitor. It is indicated for geographic atrophy (GA) secondary to age-related macular degeneration. 

Visudyne for PDT of subfoveal, predominantly classic CNVM was approved in 2000, as outlined in Medical Care.

Pegaptanib (Macugen) was approved by the FDA in 2002. Because of relatively low efficacy, it is rarely used today.

Ranibizumab (Lucentis) was approved by the FDA in 2006.

Aflibercept (Eylea) was approved by the FDA in 2011. It is the most widely used anti-VEGF agent with FDA-approved labelling for ocular indications.

Brolucizumab (Beovu) was approved by the FDA in 2019.

The bispecific antibody, faricimab (Vabysmo), was approved in 2022 for wet AMD and diabetic macular edema. 

Bevacizumab (Avastin) is an FDA-approved drug for intravenous use for the labelled indication of treatment of colorectal cancer. It is used by ophthalmologists off-label for ocular indications and requires dilution for intravitreal use by a compounding pharmacy.

In addition, various experimental protocols (eg, other antiangiogenic agents) are currently under investigation; some of these are outlined in Medical Care.


Phototherapy Agents

Class Summary

These agents are used for PDT in cases of subfoveal, predominantly classic CNV membranes.

Verteporfin (Visudyne)

Benzoporphyrin derivative monoacid (BPD-MA), consisting of equally active isomers BPD-MAC and BPD-MAD, which can be activated by low-intensity, nonthermal light of 689-nm wavelength. After activation and with oxygen, forms cytotoxic oxygen free radicals and singlet oxygen, which damages biologic structures in range of diffusion, leading to local vascular occlusion, cell damage and cell death.

Phase III data from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group showed that 61% of 402 eyes treated lost < 15 letters of visual acuity at 12 months vs 46% of 207 eyes receiving placebo (P< .001). In subgroup analysis, visual-acuity benefit persisted (67% vs 37%, P< .001) when CNV membrane was predominantly classic (50% or more of area of entire complex). Visual acuity not significantly different when the area of classic CNV membranes < 50% entire complex. Patients needed mean of about 3 treatments in first y. At most recent follow-up, patients needed mean of 5 treatments in first 2 y.


Anti-VEGF Therapy

Class Summary

This treatment reduces the risk of visual loss similar to that seen with PDT.

Aflibercept intravitreal (Eylea)

Binds and prevents activation of vascular endothelial growth factors (all forms of VEGF-A) and placental growth factor (PIGF). Indicated for neovascular (wet) age-related macular degeneration (AMD). Initial injection frequency is every 4 weeks for 3 months. After 3 once-monthly loading doses, maintenance doses may be administered every 2 months. Although not as effective as the recommended every-8-week dosing regimen, after 1 year of effective therapy, may treat with 1 dose every 12 weeks.

Brolucizumab intravitreal (Beovu, brolucizumab-dbll)

Human VEGF inhibitor; binds to the 3 major VEGF-A isoforms (eg, VEGF110, VEGF121, VEGF165), thereby preventing interaction with receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability. Indicated for adults with nAMD.

Pegaptanib (Macugen)

Selective VEGF antagonist that promotes vision stability and reduces visual acuity loss and progression to legal blindness. VEGF causes angiogenesis and increases vascular permeability and inflammation, all of which contribute to neovascularization in wet AMD

Ranibizumab (Lucentis)

Recombinant humanized IgG1-kappa isotype monoclonal antibody fragment designed for intraocular use. Indicated for neovascular (wet) AMD. In clinical trials, about one third of patients had improved vision at 12 months that was maintained by monthly injections. Binds to VEGF-A, including biologically active, cleaved form (ie, VEGF110). VEGF-A has been shown to cause neovascularization and leakage in ocular angiogenesis models and is thought to contribute to AMD disease progression. Binding VEGF-A prevents interaction with its receptors (ie, VEGFR1, VEGFR2) on surface of endothelial cells, thereby reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation. After 3 once-monthly loading doses, maintenance doses may be administered every 1 month.

Bevacizumab (Avastin)

Murine-derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting VEGF. Inhibiting new blood vessel formation denies blood, oxygen, and other nutrients needed for vascular growth. Off-label indication for exudative AMD. The need to repackage the drug from the available size vial into a smaller dose increases risk for transmission of infection if proper aseptic technique is jeopardized.

Faricimab (Vabysmo)

Bispecific antibody for treatment of adults with neovascular (wet) age-related macular degeneration. Faricimab targets 2 distinct pathways – angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). By inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization and vascular permeability. By inhibiting Ang-2, faricimab promotes vascular stability and desensitize blood vessels to the effects of VEGF-A. 


Ophthalmics, Complement Inhibitors

Class Summary

Pegcetacoplan binds to complement protein C3 and its activation fragment C3b, thereby regulating cleavage of C3 and the generation of downstream effectors of complement activation.

Pegcetacoplan intravitreal (Syfovre)

Indicated for geographic atrophy (GA) secondary to age-related macular degeneration.