What supplement is recommended for an older adult with macular degeneration?

AREDS2 Supplement Formulation for Macular Degeneration

For an older adult with macular degeneration, the AREDS2 formulation is the recommended supplement, consisting of vitamin C (500 mg), vitamin E (400 IU), zinc (25 mg), copper (2 mg), lutein (10 mg), and zeaxanthin (2 mg). 1

Who Should Take AREDS2 Supplements

Patients with intermediate AMD or advanced AMD in one eye should take AREDS2 supplements to reduce progression risk by up to 36% over 10 years. 1 This represents the only proven intervention to slow dry AMD progression. 1

High-risk features warranting supplementation include: 1, 2

• Bilateral large drusen
• Confluent drusen
• Retinal pigment epithelial (RPE) clumping or atrophy
• Advanced AMD in one eye with intermediate disease in the fellow eye
• Family history of AMD

If all at-risk patients received AREDS2 supplements, over 300,000 could delay disease progression and associated vision loss. 1

The Evidence Behind AREDS2

The original AREDS trial demonstrated that antioxidant multivitamins combined with zinc reduced progression to late AMD (OR 0.72) and visual acuity loss of more than 3 lines (OR 0.77) in patients with intermediate or advanced dry AMD. 3, 1 The combination of antioxidants and zinc reduced the risk of progression to advanced AMD and visual acuity loss of at least 15 letters (OR 0.73). 3

The AREDS2 formulation made critical improvements over the original formulation: 1, 4

• Lutein (10 mg) and zeaxanthin (2 mg) replaced beta-carotene due to an 18% increased cumulative incidence of lung cancer in current and former smokers with beta-carotene (23 lung cancers vs 11 without beta-carotene). 1
• Zinc was reduced from 80 mg to 25 mg, providing equivalent efficacy with fewer adverse effects, specifically reducing hospitalizations for genitourinary causes. 1
• Copper (2 mg) was retained to prevent copper-deficiency anemia from zinc supplementation. 1

Direct comparison studies showed lutein/zeaxanthin versus beta-carotene had a hazard ratio of 0.82 for late AMD development, 0.78 for neovascular AMD, and in patients with bilateral large drusen specifically, 0.76 for late AMD and 0.65 for neovascular AMD. 4

Critical Safety Considerations

Current or former smokers must avoid beta-carotene-containing formulations entirely due to documented lung cancer risk. 1 The American Academy of Ophthalmology explicitly recommends lutein and zeaxanthin as substitutes for this population. 1

Coordinate with the patient's primary care physician before initiating long-term AREDS2 supplementation due to potential adverse effects, particularly increased genitourinary hospitalizations with zinc. 1 The original AREDS trial reported increased hospitalization due to genitourinary causes with zinc and yellowing skin with antioxidants. 3

What AREDS2 Does NOT Do

AREDS2 supplements: 1

• Do not improve refractive errors requiring corrective lenses
• Do not treat cataracts (cataract surgery achieves visual acuity >20/40 in approximately 90% of patients)
• Have no proven benefit for early AMD without high-risk features
• Are not a substitute for anti-VEGF therapy in wet AMD

Integration with Wet AMD Treatment

For patients with neovascular (wet) AMD, AREDS2 supplements should be combined with anti-VEGF therapy, not used as a replacement. 1 Anti-VEGF injections (aflibercept, ranibizumab, or bevacizumab) must be initiated immediately upon diagnosis with three loading doses at 4-week intervals. 1 Early treatment within 2 years of diagnosis significantly reduces legal blindness and visual impairment. 1

Mandatory Lifestyle Modification

Smoking cessation is non-negotiable and must be addressed aggressively in all AMD patients. 1, 2 Cigarette smoking is the only proven modifiable risk factor for AMD, with current smokers facing 2-3 times higher risk than non-smokers, increasing proportionally to pack-years smoked. 2

Common Pitfalls to Avoid

• Do not use 80 mg zinc formulations when 25 mg provides equivalent efficacy with better safety profile. 1
• Do not recommend AREDS2 for primary prevention in healthy adults without intermediate or advanced AMD—insufficient evidence supports this use. 5
• Do not delay anti-VEGF therapy in wet AMD patients in favor of supplements alone—this represents inadequate treatment. 1
• Do not prescribe arbitrary supplement combinations lacking clinical trial support—stick to the proven AREDS2 formulation. 1