What is dry age-related macular degeneration (dry AMD) and what are the treatment options, including SYFOVRE (pegcetacoplan), for older adults with this condition?

Understanding Dry Age-Related Macular Degeneration (Dry AMD)

What is Dry AMD?

Dry AMD is a progressive eye disease where the central part of the retina (the macula) deteriorates, causing blurred central vision and difficulty with tasks like reading, but peripheral vision remains intact. 1

• Dry AMD accounts for approximately 85-90% of all AMD cases and is characterized by drusen (yellow deposits under the retina) and atrophy of the retinal pigment epithelial cells 1
• The disease involves progressive deterioration of retinal layers, which can eventually lead to geographic atrophy (advanced dry AMD) where patches of the retina become thin and non-functional 2, 3
• Unlike wet AMD, dry AMD progresses more slowly but currently has limited treatment options 1
• Central vision loss is common in advanced stages, but total blindness is extremely rare because peripheral vision is typically preserved 1

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Treatment Options for Dry AMD

AREDS2 Supplementation: The Only Proven Therapy

The American Academy of Ophthalmology recommends AREDS2 supplement formulation as the only proven intervention to slow progression of dry AMD, reducing risk by up to 36% over 10 years. 1

• The AREDS2 formulation includes: vitamin C, vitamin E, zinc (25mg), copper, lutein (10mg), and zeaxanthin (2mg) 1
• This supplementation is specifically recommended for patients with intermediate AMD or advanced AMD in one eye 1
• 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) 1
• Beta-carotene was eliminated from the AREDS2 formulation due to an 18% increased cumulative incidence of lung cancer in current and former smokers 1

Important Safety Considerations

• Zinc supplementation at 80mg was associated with increased risk of hospitalization due to genitourinary causes, which is why the dose was reduced to 25mg in AREDS2 1
• Copper must be included to prevent copper-deficiency anemia from zinc supplementation 1
• Coordination with the patient's primary care physician is recommended before initiating long-term AREDS2 supplementation due to potential adverse effects 1

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SYFOVRE (Pegcetacoplan) for Geographic Atrophy

Current Evidence and FDA Status

Pegcetacoplan is an investigational complement inhibitor that has shown efficacy in slowing the growth of geographic atrophy lesions in clinical trials, but it does not improve vision. 4

• The FILLY study demonstrated that pegcetacoplan slowed the growth of geographic atrophy lesions compared to sham injection 4
• However, pegcetacoplan did not change participants' vision during the trial 4
• After participants stopped receiving pegcetacoplan, the treatment effect appeared to be reduced 4
• Geographic atrophy represents the late stage of dry AMD where lesions form on the retina, causing patches of thin retina that ultimately lead to irreversible vision loss 4

Clinical Context

• The American Academy of Ophthalmology guidelines state that no FDA-approved therapies are currently available to slow geographic atrophy progression, but multiple agents are under investigation in clinical trials 1
• Complement cascade inhibitors represent one of the most promising directions in dry AMD treatment 5

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Other Treatment Approaches

No Alternative Pharmacologic Therapies Currently Available

There are currently no other FDA-approved medications for dry AMD beyond AREDS2 supplementation. 1

• The American Academy of Ophthalmology guidelines do not recommend any peptide-based therapies for AMD management 1
• No peptide-based therapies have FDA approval for AMD treatment, and patients should be counseled that peptide supplements lack evidence and may delay effective treatment 1

Supportive Management

• Vision rehabilitation services should be initiated immediately for patients with reduced visual function, including optical/electronic magnifying devices, bright lights, and reading aids 1, 6
• Smoking cessation is mandatory as cigarette smoking is the only proven modifiable risk factor, with current smokers facing 2-3 times higher risk of AMD progression 1, 7
• Regular comprehensive eye examinations are crucial for early detection, as early AMD is typically asymptomatic 1

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International Guideline Recommendations

American Academy of Ophthalmology Position

The American Academy of Ophthalmology recommends AREDS2 formulation as the standard of care for intermediate or advanced dry AMD, but does not currently recommend pegcetacoplan or other complement inhibitors outside of clinical trials. 1

• AREDS2 supplementation should be prescribed to all patients with intermediate AMD or advanced AMD in one eye 1
• If all patients at risk were given AREDS2 supplements, more than 300,000 could delay disease progression and associated vision loss 1
• The guidelines emphasize that early detection through regular comprehensive eye examinations is crucial, as early treatment is associated with better preservation of vision 1

Key Clinical Pitfalls to Avoid

• Do not use beta-carotene-containing formulations in current or former smokers due to documented lung cancer risk 1
• Do not use 80mg zinc formulations when 25mg provides equivalent efficacy with a better safety profile 1
• Do not delay vision rehabilitation services, as they optimize existing functional vision even though they cannot restore lost vision 1, 6
• Monitor the fellow eye aggressively every 6-12 months even without symptoms, as patients with advanced AMD in one eye remain at exceptionally high risk for progression in the other eye 6