Current and Emerging Treatment

Other anti-VEGF agents are also being studied. In October 2019, brolucizumab-dbll, a human VEGF (VEGF_A) inhibitor indicated for the treatment of neovascular (wet) AMD was approved by the FDA based on results from two Phase 3 noninferiority clinical trials, HAWK and HARRIER, that compared brolucizumab and aflibercept. Brolucizumab is administered by intravitreal injection every month for the first 3 doses, then every 8 to 12 weeks.^8,9 The FDA has also accepted the Biologics License Application (BLA) for abicipar pegol, an investigational DARPin (designed ankyrin repeat proteins) therapy, for patients with wet AMD. Abicipar pegol works by binding to and inhibiting the biologic activity of VEGF factor A with high affinity and specificity, resulting in the prevention of neovascularization and vessel permeability in the eye. The BLA was based on data from two identical noninferiority phase 3 trials, CEDAR and SEQUOIA, that evaluated the efficacy and safety of abicipar pegol, administered on day 1, week 4, and week 8, then either every 8 weeks or every 12 weeks, compared with monthly ranibizumab in treatment-naive patients with wet AMD.¹⁰

Photodynamic therapy typically is used when there is no response to initial treatment with VEGF inhibitors, and can be used alone or in combination with anti-VEGF medications.¹ A photosensitizing dye is injected intravenously and a photoactivating laser is applied through the eye immediately afterward. Neovascular tissue retains more dye than other vessels; the dye forms reactive free radicals that damage the vascular endothelium and cause thrombosis of these new vessels. Unfortunately, vessels may reopen, which would necessitate repeated therapy. The use of photodynamic therapy has decreased significantly with the increased use of anti-VEGF therapy. Thermal laser photocoagulation is a therapy that is rarely recommended.^1,3 This treatment can cause vision loss due to enlargement of current scotoma or development of a new scotoma. Any use of this treatment should be limited to areas outside the macula.¹

Emerging Targets

The identification of modifiable risk factors and the development of future preventive treatments are crucial because there is currently no available treatment of dry AMD. Because dry AMD has no approved treatment, efforts focus on understanding the pathophysiology of the disease for the scientific development of rationale treatments. Several innovative treatments for dry Age-Related Macular Degeneration are in progress;⁷ some studies have used medication to target the inflammation associated with AMD, while others have looked at therapies that reduce the effects of oxidative stress. Researchers also have considered stem cell-based therapies to regenerate damaged photoreceptors and retinal pigment epithelium.^1,11

Three AMD therapies that were not successful recently include lampalizumab, humanized monoclonal antibody (Fab fragment), that is a selective inhibitor of complement factor D, for dry AMD; and pegpleranib/E10030, which is an inhibitor of platelet-derived growth factor (anti-PDGF) aptamer that binds to PDGF; and OHR-102, squalamine eye drop; for wet AMD.¹²

Other treatment modalities under investigation for wet AMD include the role of stereotactic radiotherapy (ie, use of a low-voltage external beam) as adjunctive treatments to anti-VEGF therapy to reduce the frequency of intravitreal injections needed while maintaining visual acuity and other modulators of angiogenesis.⁷