What is the recommended treatment for dry and wet age‑related macular degeneration?

Treatment for Macular Degeneration

Wet (Neovascular) AMD: Immediate Anti-VEGF Therapy Required

For wet AMD, initiate intravitreal anti-VEGF therapy immediately upon diagnosis with three loading doses at 4-week intervals using aflibercept, ranibizumab, bevacizumab, or brolucizumab. 1, 2

Loading Phase Protocol

• Administer three loading doses at exactly 4-week intervals (approximately every 25-31 days for brolucizumab) 2
• Available agents include:
  • Aflibercept: Preferred for its every-8-week maintenance dosing advantage after loading 2
  • Ranibizumab: Monthly or individualized regimens 3
  • Bevacizumab: Off-label use, exercise caution with PRN dosing as it may be slightly less effective 3, 2
  • Brolucizumab: Every 8-12 weeks maintenance, noninferior to aflibercept with superior fluid resolution 2

Maintenance Regimens

After completing the loading phase, choose from evidence-based protocols 3, 1:

• Aflibercept every 8 weeks: Achieves 95.1-95.6% of patients maintaining vision (losing <15 letters), equivalent to monthly ranibizumab 2
• Treat-and-extend: Gradually increase intervals once disease stabilizes, showing similar efficacy to monthly injections with reduced treatment burden 3, 4
• PRN (as-needed): Treat based on OCT evidence of fluid or visual acuity decline, though monthly regimens provide approximately 1.7 letters better visual acuity 3, 4
• Fixed monthly: Slightly more effective than PRN but higher treatment burden 4

Critical pitfall: PRN bevacizumab may be slightly less effective than other anti-VEGF regimens and should be used with caution 3

Monitoring Requirements

At every visit, perform 2, 4:

• OCT imaging: Assess for subretinal or intraretinal fluid
• Biomicroscopic fundus examination
• Fluorescein angiography: When clinically indicated
• Patients must report endophthalmitis symptoms, retinal detachment, or vision decrease immediately 2

Safety Profile

• Endophthalmitis risk: ≤1.0% cumulative over 1-2 years for aflibercept/ranibizumab, 0.16% per injection for bevacizumab 2
• Bevacizumab carries higher systemic serious adverse event rates (24% vs 19% for ranibizumab, persistent at 2 years) 3, 2
• Retinal detachment, retinal tear, vitreous hemorrhage are rare but possible 2
• RPE tears may occur but are not contraindications to continued therapy 3

Long-Term Outcomes

• At 5-year follow-up, 50% of patients maintained visual acuity of 20/40 3, 2
• Early treatment within 2 years of diagnosis significantly reduces legal blindness and visual impairment 1

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Dry (Non-Neovascular) AMD: AREDS2 Supplementation

For intermediate or advanced dry AMD, prescribe AREDS2 formulation supplements to reduce progression risk by up to 36% over 10 years. 1, 4

AREDS2 Formulation Components

The recommended formulation includes 1:

• Vitamin C
• Vitamin E
• Zinc 25mg (equivalent efficacy to 80mg with better safety profile) 1
• Copper (prevents copper-deficiency anemia from zinc) 1
• Lutein 10mg
• Zeaxanthin 2mg

Critical formulation change: Lutein and zeaxanthin replaced beta-carotene due to 18% increased cumulative incidence of lung cancer in current and former smokers (relative risk 1.28) 1

Who Should Receive AREDS2 Supplements

• Patients with intermediate AMD 1
• Patients with advanced AMD in one eye 1
• High-risk features: bilateral soft drusen, confluent drusen, RPE clumping or atrophy, family history 1

Safety Considerations

• Coordinate with primary care physician before initiating long-term supplementation due to potential adverse effects 1
• Zinc at 80mg associated with increased genitourinary hospitalizations; 25mg dose recommended 1
• Never use beta-carotene formulations in current or former smokers 1

Evidence Base

• Original AREDS trial demonstrated antioxidants plus zinc reduced progression to late AMD (OR 0.72) and visual acuity loss >3 lines (OR 0.77) 1
• If all at-risk patients received supplements, over 300,000 could delay disease progression 1

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Essential Risk Factor Modification

Smoking cessation is mandatory as cigarette smoking increases AMD progression risk proportional to pack-years smoked 1

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Geographic Atrophy (Advanced Dry AMD)

• No FDA-approved therapies currently available to slow geographic atrophy progression 1
• Multiple agents under investigation in clinical trials, including complement pathway inhibitors 5
• Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have shown phase 3 evidence of reducing geographic atrophy growth 5

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Fellow Eye Monitoring

For patients with wet AMD in one eye 1, 2:

• Fellow eye remains at exceptionally high risk (up to 36% over 10 years)
• Monitor every 6-12 months even without symptoms to detect asymptomatic CNV at a treatable stage
• Prescribe AREDS2 supplements to reduce fellow eye risk by 36% over 10 years 1
• Instruct patients to use Amsler grid for self-monitoring of metamorphopsia 1

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Vision Rehabilitation

• Central vision loss is common, but total blindness is extremely rare 1
• Peripheral vision typically preserved 1
• Refer patients with reduced visual function to vision rehabilitation services immediately 1
• Options include optical/electronic magnifying devices, bright lights, and electronic reading aids 1
• Charles Bonnet syndrome (visual hallucinations) may occur but does not represent psychosis 1