Age-Related Macular Degeneration

name: Age-Related Macular Degeneration
creation_date: '2025-12-18T17:01:35Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Ophthalmological Disease
disease_term:
  preferred_term: age-related macular degeneration
  term:
    id: MONDO:0005150
    label: age-related macular degeneration
has_subtypes:
- name: Dry AMD (Atrophic)
  description: Gradual degeneration with drusen and geographic atrophy, 85-90%
    of cases.
- name: Wet AMD (Neovascular)
  description: Abnormal blood vessel growth, causes rapid vision loss, 10-15% of
    cases.
pathophysiology:
- name: Drusen Accumulation
  description: >
    Lipid and protein deposits accumulate between retinal pigment
    epithelium and Bruch's membrane. Drusen indicate RPE dysfunction
    and are early hallmark of AMD.
  cell_types:
  - preferred_term: Retinal Pigment Epithelial Cell
    term:
      id: CL:0002586
      label: retinal pigment epithelial cell
  evidence:
  - reference: PMID:38731137
    reference_title: "Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response."
    supports: SUPPORT
    snippet: "Drusen comprise a yellowish white substance that accumulates typically
      under the retinal pigment epithelium (RPE), and their constituents are lipids,
      complement, amyloid, crystallin, and others."
    explanation: This confirms that drusen are lipid and protein deposits under
      the RPE with characteristic composition including lipids, complement
      proteins, and other components.
- name: RPE Dysfunction and Loss
  description: >
    Oxidative stress, lipofuscin accumulation, and inflammation
    damage RPE cells. RPE loss leads to photoreceptor death and
    geographic atrophy in dry AMD.
  biological_processes:
  - preferred_term: Oxidative Stress Response
    term:
      id: GO:0006979
      label: response to oxidative stress
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: PARTIAL
    snippet: "AMD occurs when extracellular deposits accumulate in the outer retina,
      ultimately leading to photoreceptor degeneration and loss of central vision.
      The late stages of AMD are characterized by outer retinal atrophy, termed geographic
      atrophy, or neovascularization associated with subretinal and/or intraretinal
      exudation, termed exudative neovascular AMD."
    explanation: This describes the progression from deposit accumulation to
      photoreceptor degeneration and atrophy, supporting the role of RPE
      dysfunction in geographic atrophy development.
- name: Complement Dysregulation
  description: >
    Excessive complement activation in the macula contributes to
    chronic inflammation and tissue damage. CFH variants are major
    genetic risk factor.
  biological_processes:
  - preferred_term: Complement Activation
    term:
      id: GO:0006956
      label: complement activation
  evidence:
  - reference: PMID:38690727
    reference_title: "Complement regulation in the eye: implications for age-related macular degeneration."
    supports: PARTIAL
    snippet: "Careful regulation of the complement system is critical for enabling
      complement proteins to titrate immune defense while also preventing collateral
      tissue damage from poorly controlled inflammation. In the eye, this balance
      between complement activity and inhibition is crucial, as a low level of basal
      complement activity is necessary to support ocular immune privilege, a prerequisite
      for maintaining vision."
    explanation: This explains the importance of complement regulation in the
      eye and how dysregulation leads to inflammation and tissue damage, which
      is central to AMD pathogenesis.
  - reference: PMID:38690727
    reference_title: "Complement regulation in the eye: implications for age-related macular degeneration."
    supports: SUPPORT
    snippet: "Complement dysregulation has been implicated in many ocular diseases,
      including glaucoma, diabetic retinopathy, and age-related macular degeneration
      (AMD)."
    explanation: Direct confirmation that complement dysregulation is implicated
      in AMD pathogenesis.
- name: Choroidal Neovascularization
  description: >
    In wet AMD, VEGF-driven abnormal blood vessel growth from choroid
    invades through Bruch's membrane. These fragile vessels leak and
    bleed, causing rapid vision loss.
  biological_processes:
  - preferred_term: Angiogenesis
    term:
      id: GO:0001525
      label: angiogenesis
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: PARTIAL
    snippet: "In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal
      anti-vascular endothelial growth factor (anti-VEGF) injections experience less
      than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving
      sham treatment."
    explanation: The effectiveness of anti-VEGF therapy demonstrates that
      VEGF-driven angiogenesis is the key pathophysiological mechanism in
      neovascular AMD.
phenotypes:
- name: Central Vision Loss
  category: Ophthalmological
  frequency: VERY_FREQUENT
  diagnostic: true
  phenotype_term:
    preferred_term: Central Vision Loss
    term:
      id: HP:0000551
      label: Color vision defect
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: SUPPORT
    snippet: "AMD occurs when extracellular deposits accumulate in the outer retina,
      ultimately leading to photoreceptor degeneration and loss of central vision."
    explanation: Confirms that central vision loss is a direct consequence of
      AMD pathophysiology through photoreceptor degeneration.
- name: Metamorphopsia
  category: Ophthalmological
  frequency: FREQUENT
  notes: Distortion of straight lines
  phenotype_term:
    preferred_term: Visual Distortion
    term:
      id: HP:0000505
      label: Visual impairment
- name: Difficulty Reading
  category: Ophthalmological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Reading Difficulty
    term:
      id: HP:0000505
      label: Visual impairment
- name: Scotoma
  category: Ophthalmological
  frequency: FREQUENT
  notes: Central blind spot
  phenotype_term:
    preferred_term: Central Scotoma
    term:
      id: HP:0001123
      label: Visual field defect
- name: Decreased Contrast Sensitivity
  category: Ophthalmological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Reduced Contrast Sensitivity
    term:
      id: HP:0000505
      label: Visual impairment
biochemical:
- name: VEGF
  presence: Elevated
  context: In wet AMD, drives neovascularization
- name: Complement factors
  presence: Elevated
  context: C3a, C5a in drusen and plasma
genetic:
- name: CFH
  association: Risk Factor
  notes: Complement factor H, Y402H variant
- name: ARMS2/HTRA1
  association: Risk Factor
  notes: 10q26 locus
- name: C3
  association: Risk Factor
  notes: Complement component 3
- name: CFB
  association: Risk Factor
  notes: Complement factor B
environmental:
- name: Age
  notes: Primary risk factor, rare before 50
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: SUPPORT
    snippet: "The annual incidence of AMD ranges from 0.3 per 1000 in people who are
      aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older."
    explanation: Demonstrates the strong age-dependent increase in AMD
      incidence, with over 100-fold higher incidence in the oldest age groups.
- name: Smoking
  notes: 2-4x increased risk
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: SUPPORT
    snippet: "Long-term prospective cohort studies show a significantly higher AMD
      incidence in people who smoke more than 20 cigarettes per day compared with
      people who never smoked."
    explanation: Confirms smoking as a significant environmental risk factor for
      AMD based on long-term cohort studies.
- name: Family History
  notes: Strong genetic component
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: SUPPORT
    snippet: "The estimated heritability of late-stage AMD is approximately 71% (95%
      CI, 18%-88%)."
    explanation: Quantifies the strong genetic component of AMD, with
      heritability estimates showing that genetic factors account for
      approximately 71% of risk for late-stage disease.
- name: Cardiovascular Disease
  notes: Shared risk factors
- name: Obesity
  notes: Increases risk of progression
- name: UV Light Exposure
  notes: May contribute to oxidative damage
treatments:
- name: Anti-VEGF Injections
  description: First-line for wet AMD (ranibizumab, aflibercept, bevacizumab).
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: SUPPORT
    snippet: "In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal
      anti-vascular endothelial growth factor (anti-VEGF) injections experience less
      than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving
      sham treatment."
    explanation: Demonstrates the efficacy of anti-VEGF therapy as first-line
      treatment for neovascular AMD, with significant preservation of visual
      acuity compared to placebo.
- name: AREDS2 Supplements
  description: Vitamins C, E, zinc, lutein, zeaxanthin slow dry AMD progression.
  evidence:
  - reference: PMID:38193957
    reference_title: "Age-Related Macular Degeneration: A Review."
    supports: SUPPORT
    snippet: "Individuals with AMD who take nutritional supplements consisting of
      high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability
      to progress to late-stage AMD at 5 years vs a 28% probability for those taking
      a placebo."
    explanation: Quantifies the protective effect of AREDS-type nutritional
      supplementation in reducing progression to late-stage AMD by approximately
      8 percentage points over 5 years.
- name: Photodynamic Therapy
  description: Rarely used now, for select wet AMD cases.
- name: Low Vision Rehabilitation
  description: Magnifiers, adaptive devices for advanced disease.
- name: Complement Inhibitors
  description: Pegcetacoplan for geographic atrophy (newer treatment).
- name: Smoking Cessation
  description: Reduces progression risk.
classifications:
  harrisons_chapter:
  - classification_value: nervous system disorder
datasets:
references:
- reference: DOI:10.1016/j.ajo.2024.02.021
  title: 'Drug Approval for the Treatment of Geographic Atrophy: How We Got Here and
    Where We Need to Go'
  findings: []
- reference: DOI:10.1096/fj.202401160rr
  title: Retinal G‐protein‐coupled receptor deletion exacerbates
    <scp>AMD</scp>‐like changes via the <scp>PINK1</scp>–parkin pathway under
    oxidative stress
  findings: []
- reference: DOI:10.1172/jci178296
  title: 'Complement regulation in the eye: implications for age-related macular degeneration'
  findings: []
- reference: DOI:10.3389/fphar.2024.1410172
  title: 'Efficacy and safety of complement inhibitors in patients with geographic
    atrophy associated with age-related macular degeneration: a network meta-analysis
    of randomized controlled trials'
  findings: []
- reference: DOI:10.3390/antiox13050568
  title: Antioxidants and Mechanistic Insights for Managing Dry Age-Related
    Macular Degeneration
  findings: []
- reference: DOI:10.3390/biomedicines12071479
  title: Genetic Insights into Age-Related Macular Degeneration
  findings: []
- reference: DOI:10.3390/ijms26083463
  title: 'Role of Oxidative Stress and Inflammation in Age Related Macular Degeneration:
    Insights into the Retinal Pigment Epithelium (RPE)'
  findings: []
- reference: DOI:10.3390/jcm13092608
  title: Drusen in AMD from the Perspective of Cholesterol Metabolism and
    Hypoxic Response
  findings: []
- reference: DOI:10.3390/medicina60101647
  title: 'Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting
    Approaches, and Recent Developments in Nanotherapeutics'
  findings: []