What is Age-related Macular Degeneration (AMD)?

Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is a degenerative disease of the retina affecting individuals over 55 years of age, characterized by the presence of drusen and retinal pigment epithelium alterations, which can progress to severe central vision loss and is the leading cause of blindness in industrialized countries. 1

Definition and Classification

AMD is a complex multifactorial eye disease involving metabolic, functional, genetic, and environmental factors with inflammatory components. It primarily affects the macula, the central area of the retina responsible for sharp, central vision.

AMD is classified into stages:

• Early AMD: Characterized by small to intermediate drusen with minimal visual symptoms
• Intermediate AMD: Larger drusen and pigmentary abnormalities with mild visual symptoms
• Advanced (Late) AMD: Divided into two forms:
  • Dry (non-exudative/atrophic) AMD: Geographic atrophy involving the center of the macula
  • Wet (exudative/neovascular) AMD: Features choroidal neovascularization (CNV) 2, 1

Epidemiology

• Worldwide prevalence projected to increase from 196 million in 2020 to 288 million by 2040 3
• Prevalence increases dramatically with age:
  • 0.3% in ages 60-64
  • 16.4% in ages 80 and older 1
• Leading cause of blindness in industrialized countries 3

Pathophysiology

AMD develops through several key processes:

1. Lipofuscinogenesis: Accumulation of lipofuscin in RPE cells
2. Drusogenesis: Formation of drusen (yellow deposits beneath the retina)
3. Inflammation: Chronic inflammation involving complement system activation
4. Neovascularization: Abnormal blood vessel growth in wet AMD 4, 5

The disease progression involves:

• Dysfunction and degeneration of the retinal pigment epithelium (RPE)
• Oxidative stress and mitochondrial dysfunction
• Altered proteostasis and lipid homeostasis
• Extracellular matrix dysregulation
• Choriocapillaris degeneration 5

Risk Factors

Major risk factors include:

• Age: Most significant risk factor
• Genetics: 46-71% of disease contribution, with CFH and ARMS2/HTRA1 being the most notable risk loci 6
• Smoking: Most consistently proven modifiable risk factor 1, 7
• Metabolic factors: Body mass index, lipid metabolism 1
• Family history: Increased risk with positive family history 1
• Presence of drusen: Especially soft, large, or confluent drusen 1

Diagnosis

Diagnosis involves:

• Clinical examination: Detection of drusen (yellow lesions at the level of the RPE basement membrane)
• Drusen classification:
  • Small (< 63 μm)
  • Intermediate (≥ 63 μm and ≤ 125 μm)
  • Large (> 125 μm) 1
• Amsler grid testing: Detection of metamorphopsia (visual distortion)
• Fluorescein angiography: Classification of CNV (classic vs. occult)
• Advanced imaging techniques: OCT, adaptive optics retinal imaging 1, 7

Management

Treatment approaches differ based on AMD type:

Dry AMD

• AREDS2 supplementation (vitamins C, E, zinc, copper, lutein, and zeaxanthin) for high-risk patients 1
• Lifestyle modifications:
  • Smoking cessation
  • Maintaining healthy body mass index
  • Regular exercise 1, 7

Wet AMD

• Intravitreal anti-VEGF injections as first-line treatment
• Prompt initiation is critical for best outcomes 1

Monitoring and Prevention

• Regular monitoring of high-risk patients (those with drusen, diabetes)
• Early detection is crucial for effective treatment
• Nutritional and lifestyle interventions can reduce progression risk 1, 7

Clinical Implications

AMD has profound impacts on:

• Quality of life
• Independence
• Psychological well-being
• Healthcare costs 3

Early detection and intervention are essential to preserve vision and maintain quality of life in affected individuals.