First-Line Treatment for Age-Related Macular Degeneration
For neovascular (wet) AMD, initiate intravitreal anti-VEGF therapy immediately with aflibercept, ranibizumab, or bevacizumab using three loading doses at 4-week intervals, as this is the gold standard treatment that must be started as soon as diagnosis is confirmed. 1, 2, 3
Treatment Algorithm Based on AMD Type
Neovascular (Wet) AMD - Primary Treatment
Anti-VEGF therapy is the only effective first-line treatment for wet AMD and should never be delayed. 1, 2, 3
Initial Loading Phase:
- Administer three loading doses at exactly 4-week intervals 2, 3
- Choose from FDA-approved agents: aflibercept, ranibizumab, or brolucizumab 1, 3, 4
- Bevacizumab is used off-label but may be slightly less effective than other regimens 1, 3
Maintenance Regimens (after loading):
- Aflibercept every 8 weeks - comparable efficacy to monthly dosing in first year 3
- Treat-and-extend - similar efficacy to monthly injections while reducing treatment burden 1, 3
- PRN (as-needed) - approximately 1.7 letters worse visual acuity than monthly regimens 3
- Monthly injections - most effective but highest treatment burden 1, 3
Critical timing consideration: Early treatment within 2 years of diagnosis significantly reduces legal blindness and visual impairment 2
Non-Neovascular (Dry) AMD - Primary Treatment
AREDS2 supplementation is the only proven intervention to slow progression of dry AMD, reducing risk by up to 36% over 10 years. 2, 3
AREDS2 Formulation Components:
- Vitamin C 2, 3
- Vitamin E 2, 3
- Zinc 25mg (not 80mg - equivalent efficacy with better safety profile) 2
- Copper (prevents copper-deficiency anemia from zinc) 2
- Lutein 10mg 2, 3
- Zeaxanthin 2mg 2, 3
Who requires AREDS2 supplementation:
- Patients with intermediate AMD 2, 3
- Patients with advanced AMD in one eye 2, 3
- High-risk features: bilateral soft drusen, confluent drusen, RPE clumping or atrophy 2
Critical safety consideration: Beta-carotene was eliminated from AREDS2 due to 18% increased cumulative incidence of lung cancer in current and former smokers (relative risk 1.28) 2
Monitoring Requirements
For all patients on anti-VEGF therapy:
- OCT imaging at each visit to assess for subretinal or intraretinal fluid 2, 3
- Biomicroscopic fundus examination 3
- Fluorescein angiography as needed 3
- Immediate reporting of endophthalmitis symptoms, retinal detachment, or decreased vision 2, 3
For patients with unilateral wet AMD:
- Fellow eye remains at exceptionally high risk 2
- Monitor every 6-12 months even without symptoms 2
- AREDS2 supplements lower fellow eye risk by 36% over 10 years 2
Evidence Quality and Comparative Effectiveness
The CATT trial demonstrated that bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year (bevacizumab monthly: 8.0 letters gained; ranibizumab monthly: 8.5 letters gained), though bevacizumab was associated with higher rates of serious systemic adverse events (39.9% vs 31.7%) 5, 6. At 2-year follow-up, mean gain remained similar between drugs (bevacizumab-ranibizumab difference: -1.4 letters), but monthly treatment was superior to PRN (difference: -2.4 letters) 5.
Brolucizumab achieved noninferiority to aflibercept at week 48 with superior reductions in central subfield thickness and fewer patients with subretinal, intraretinal, and sub-RPE fluid 1, 3.
Common Pitfalls to Avoid
Do not delay anti-VEGF therapy for wet AMD - every week of delay worsens prognosis 2
Do not use beta-carotene formulations in current or former smokers - documented lung cancer risk with 23 lung cancers in beta-carotene group versus 11 in no beta-carotene group 2
Do not use 80mg zinc when 25mg provides equivalent efficacy - higher dose increases genitourinary hospitalizations 2
Do not switch from monthly to PRN treatment prematurely - results in greater mean decrease in vision (-2.2 letters) and lower proportion without fluid (-19%) 5
Mandatory smoking cessation - cigarette smoking increases AMD progression risk proportional to pack-years smoked 2
Complications and Safety Profile
Anti-VEGF injection risks:
- Endophthalmitis: 0.019-0.09% per injection (lower with PRN versus monthly) 3
- Retinal tear or detachment 1, 3
- Non-infectious inflammation 1, 3
- Theoretical systemic arteriothrombolic events (clinical trial results inconclusive) 1, 3
- RPE tears/rips (not a contraindication to continued therapy) 1, 3
AREDS2 supplementation risks:
- Increased genitourinary hospitalizations with 80mg zinc 2
- Coordinate with primary care physicians before initiating long-term supplementation 2
Long-Term Outcomes
50% of patients maintained visual acuity of 20/40 at 5-year follow-up in CATT trials 1, 3. Eyes that do not develop subretinal fibrosis or macular atrophy maintain their initial 6-month visual improvement over 3 years 7. Central vision loss is common, but total blindness is extremely rare as peripheral vision remains preserved 2.