Treatment of Drusen in Age-Related Macular Degeneration
The treatment of drusen depends entirely on AMD stage: no intervention for early AMD with small drusen, AREDS2 supplementation plus smoking cessation for intermediate AMD with large drusen (≥125 μm), and immediate anti-VEGF therapy if neovascular AMD develops. 1, 2
Risk Stratification Based on Drusen Characteristics
The first step is determining AMD stage based on drusen size and associated retinal pigment epithelium (RPE) changes:
- Early AMD: Medium-sized drusen with minimal RPE changes—no treatment indicated beyond monitoring every 6-12 months 3, 2
- Intermediate AMD: Large drusen ≥125 μm, bilateral soft drusen, confluent drusen, or RPE clumping/atrophy—requires immediate intervention 1, 2
- Advanced AMD: Geographic atrophy or neovascular disease—requires specialized treatment 2
Treatment Protocol for Intermediate AMD
For patients with large drusen (≥125 μm) bilaterally or with RPE alterations, initiate AREDS2 supplementation immediately to reduce progression risk by up to 36% over 10 years. 1
The AREDS2 formulation consists of:
- Vitamin C
- Vitamin E
- Zinc 25 mg
- Copper
- Lutein 10 mg
- Zeaxanthin 2 mg 1
Mandatory Smoking Cessation
Smoking cessation counseling must occur at every clinical visit, as cigarette smoking is the only proven modifiable risk factor that prevents AMD progression, with current smokers facing 2-3 times higher risk proportional to pack-years smoked. 1, 2
Patient Self-Monitoring
Provide an Amsler grid for daily home monitoring and instruct patients to return immediately for any new visual symptoms, particularly metamorphopsia, as early detection of neovascular conversion is critical for visual prognosis 1
High-Risk Features Requiring Closer Surveillance
Patients with the following characteristics warrant more frequent monitoring:
- Bilateral large drusen ≥125 μm 1, 2
- Confluent drusen 1, 4
- RPE clumping or atrophy 1, 2
- Family history of AMD 1, 2
- Current smoking status 1, 2
Treatment of Advanced AMD
If neovascular AMD develops, initiate intravitreal anti-VEGF therapy immediately with three loading doses at 4-week intervals, followed by maintenance therapy every 8 weeks or treat-and-extend protocols. 2
For geographic atrophy, continue AREDS2 supplementation to slow progression, though no FDA-approved therapies currently exist to reverse this condition 2
Important Caveats
- Drusen themselves cause structural and molecular abnormalities in overlying photoreceptors and Müller glial cells, with rod opsin mislocalization and cone opsin decreased immunoreactivity even over small subclinical drusen 5
- The presence of drusen indicates diffuse thickening of Bruch's membrane with basal linear deposits, creating a potential cleavage plane for choroidal neovascularization growth 4
- Oxidative protein modifications, including carboxyethyl pyrrole adducts from docosahexaenoate-containing lipid oxidation, are more abundant in AMD Bruch's membrane and strongly support oxidative injury as a contributor to AMD pathogenesis 6
- In young patients (under 45 years), drusen are virtually never AMD-related and hereditary drusen should be considered instead—AREDS2 supplementation is NOT indicated in this population 3