Stages of Maculopathy
Age-related macular degeneration is classified into three distinct stages: early AMD (characterized by medium-sized drusen ≥63 μm and retinal pigmentary changes), intermediate AMD (large drusen ≥125 μm with confluent drusen and RPE clumping or atrophy), and late AMD (subdivided into geographic atrophy and neovascular/exudative disease). 1, 2, 3
Early AMD
Clinical Features:
- Medium-sized drusen (≥63 μm but <125 μm) with or without retinal pigmentary abnormalities 2, 3
- Hypopigmented or hyperpigmented changes in the retinal pigment epithelium 1
- Typically asymptomatic with preserved visual acuity 1
- Bilateral soft drusen are a key high-risk feature 1
Prevalence by ethnicity (age ≥45):
- White Americans: 4.8% 1
- African descent: 2.1% 1
- Hispanic descent: 4.0-7.5% 1
- Asian descent (age 40-79): 6.8% 1
Risk factors at this stage include: increasing age, bilateral soft drusen, family history, genetic polymorphisms (particularly CFH and ARMS2 genes), smoking, and poor diet/nutrition 1, 2
Intermediate AMD
Clinical Features:
- Large drusen (≥125 μm), confluent drusen, or extensive intermediate drusen 1, 3
- Clumping or atrophy of retinal pigment epithelium 1
- Retinal pigment epithelial detachments may be present 1
- Visual symptoms may begin to emerge but are often subtle 1, 3
Critical management point: This stage represents the population for whom AREDS2 supplementation (vitamin C, vitamin E, zinc, copper, lutein 10mg, zeaxanthin 2mg) should be strongly considered, as it reduces progression risk to advanced AMD by up to 36% over 10 years 1, 4
An estimated 8 million persons aged ≥55 years in the United States have monocular or binocular intermediate AMD or monocular advanced AMD, representing the high-risk population that could benefit from preventive supplementation 1
Late AMD (Advanced Disease)
Late AMD is subdivided into two forms that can coexist 2, 3:
Geographic Atrophy (Dry/Atrophic AMD)
Clinical Features:
- Well-demarcated areas of RPE atrophy with visible underlying choroidal vessels 1, 5
- Progressive loss of photoreceptors and RPE cells 2, 6
- Accounts for approximately 85-90% of all AMD cases 4
- Slower progression compared to neovascular AMD but leads to irreversible central vision loss 4, 6
Prevalence by ethnicity (age ≥45):
- White Americans: 0.6% 1
- African descent: 0.3% 1
- Hispanic descent: 0.2% 1
- Asian descent (age 40-79): 0.56% 1
Management: Currently no FDA-approved therapies exist to reverse geographic atrophy, though AREDS2 supplementation remains indicated to slow progression 4
Neovascular/Exudative AMD (Wet AMD)
Clinical Features:
- Choroidal neovascularization with abnormal blood vessel growth beneath the retina 4, 2
- Subretinal or intraretinal hemorrhage, lipid exudates, and fluid accumulation 1
- Retinal pigment epithelial detachments 1
- Rapid progression with severe vision loss if untreated 4, 2
Diagnostic findings on OCT: Subretinal fluid, intraretinal fluid, or subretinal hyperreflective material indicating active neovascularization 4
Management algorithm: Immediate initiation of intravitreal anti-VEGF therapy (aflibercept, ranibizumab, or bevacizumab) with three loading doses at 4-week intervals, followed by maintenance therapy every 8 weeks or treat-and-extend protocols 4, 7
Treatment outcomes: 94.6% of patients receiving monthly anti-VEGF injections experience less than 15-letter visual acuity loss at 12 months compared to 62.2% receiving sham treatment 7
Critical Risk Stratification for Progression
Patients at highest risk for progression to late AMD include those with:
- Bilateral large drusen (≥125 μm) 1
- Confluent drusen 1
- RPE clumping or atrophy 1
- Family history of AMD 1, 8
- Current smoking (2-3 times higher risk) 8, 2
- Advanced AMD in one eye (fellow eye at exceptionally high risk) 4
Common Pitfalls to Avoid
Do not delay AREDS2 supplementation in patients with intermediate AMD or advanced AMD in one eye—more than 300,000 patients could delay disease progression if appropriately supplemented 1
Do not use beta-carotene-containing formulations in current or former smokers due to documented 18% increased lung cancer risk 4
Do not delay anti-VEGF therapy in neovascular AMD—early treatment within 2 years of diagnosis significantly reduces legal blindness and visual impairment 4
Smoking cessation is mandatory at all stages, as cigarette smoking increases AMD progression risk proportional to pack-years smoked 1, 8