Current and Emerging Treatment

All patients with AMD should be educated about healthy lifestyle choices including regular exercise; smoking cessation; wearing protective eyewear in the sun; and a diet that incorporates fruits, vegetables, fish, and nuts.¹ Early recognition and coordinated care between primary care providers and vision specialists will lead to timely management, which may decrease the incidence of permanent blindness due to AMD.¹

Once visual acuity has reached the point in which self-care becomes difficult, referral to a low-vision rehabilitation specialist becomes a vital part of care.^1,2 Providers can monitor this on a regular basis. No approved treatment exists for early Age-Related Macular Degeneration; however current research is evaluating approaches to managing early to intermediate AMD, particularly dry AMD. Patients may be given an Amsler grid to self-evaluate on a weekly basis for any changes in vision, such as missing areas of the grid or distorted/wavy lines.¹ See the Figure below for an example of a patient self-evaluation of visual changes using an Amsler grid.

Providers also can ask patients to test their vision in each eye by regularly covering one eye at a time and reading, noting any new changes in vision. Follow-up should be arranged anywhere from 6 to 24 months, with the understanding that patients should return promptly if they experience any new symptoms. Two benchmark studies sponsored by the National Institutes of Health, the Age-Related Eye Disease Study 1 and 2 (AREDS 1 and 2), provided evidence supporting that nutritional supplements can reduce the risk of progression to advanced AMD.^1,3 Based on the results from AREDS 1 and 2, patients with intermediate AMD, noncentral AMD, advanced AMD, or vision loss in one eye due to AMD are advised to take a combination of antioxidant supplements and zinc. Patients should also follow up with their ophthalmologist every 6 to 18 months or sooner if any new symptoms develop.¹

For patients with wet AMD, first-line therapy is intravitreal injections with VEGF inhibitors, which limit the destructive effects of neovascularization on retinal tissue. These injections can stabilize or possibly reverse vision loss.^1,4Large randomized clinical trials have found similar results in efficacy with the use of both ranibizumab and bevacizumab.^1,5 Aflibercept has had comparable results to both ranibizumab and bevacizumab, but with a longer duration of action; ranibizumab and bevacizumab are injected every 4 weeks and aflibercept every 8 weeks.¹ (see Table below for results from selected studies of commonly used anti-VEGF therapies) Higher molar concentration aflibercept (8mg) was recently FDA-approved for the treatment of nAMD (PULSAR), with injections every 8-16 weeks after 3 initial monthly doses.⁶ Therapy should be initiated at the first signs and symptoms of neovascular disease. Any delay in therapy (more than 21 weeks) is associated with poorer vision outcomes.^1,7

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.^9,10 Faricimab, a bispecific antibody inhibiting VEGF-A and Ang-2, has also been FDA-approved for the treatment of wet AMD (TENAYA/LUCERNE).¹⁸ 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.¹¹

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;⁸ 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.^1,12

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.¹³

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.⁸

Clinical Toolkit

Pathophysiology

Diagnosis and Risk Factors

AMD Management