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

Updated: Aug 28, 2023
  • Author: F Ryan Prall, MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Medication Summary

Intravitreal injections with vascular endothelial growth factors (VEGF) inhibitors (eg, aflibercept, ranibizumab, brolucizumab, faricimab) are used to reduce the progression of exudative AMD.

Complement inhibitors, such as pegcetacoplan intravitreal (Syfovre) and avacincaptad pegol intravitreal (Izervay), are indicated for geographic atrophy (GA) secondary to age-related macular degeneration. 


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, Eylea HD)

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 are administered. Frequency of maintenance doses is dependent on which product is being administered (ie, original formulation or high-dose). 

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.

Ranibizumab intravitreal injection (Lucentis, Byooviz, Cimerli)

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.

Ranibizumab intravitreal implant (Susvimo)

Indicated for treatment of neovascular (wet) AMD in patients who have previously responded to at least 2 intravitreal injections of a VEGF inhibitor. 

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

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

Pegcetacoplan intravitreal (Syfovre)

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

Avacincaptad pegol intravitreal (Izervay)

Pegylated oligonucleotide that binds to and inhibits complement protein C5. Inhibiting C5 may prevent its cleavage to C5a and C5b thus decreasing membrane attack complex (MAC) formation.