Macular Degeneration, Age-Related



  • Age-related macular degeneration (AMD) is the leading cause of irreversible, severe visual loss in persons age >65 years.
  • AMD can be classified as:
    • Atrophic/nonexudative, such as drusen or macular pigmentary changes
    • Neovascular/exudative or neovascular age-related macular degeneration (nAMD)


  • nAMD form is rare in blacks and more common in whites.
  • Predominant sex: female


  • In the Framingham Eye Study (FES), drusen were noted in 25% of all participants who were ≥52 years of age. AMD-associated visual loss was noted in 5.7%.
  • Atrophic/nonexudative stage accounts for 20% of cases of severe visual loss.
  • nAMD stage accounts for 80% of cases of severe visual loss.

Per FES study:

  • People 65 to 74 years old: 11%
  • People ≥75 years old: 27.9%

Etiology and Pathophysiology

  • Atrophic/nonexudative
    • Drusen and/or pigmentary changes in the macula. Drusen are deposits of hyaline material between the RPE and Bruch’s membrane (the limiting membrane between the RPE and the choroid).
    • Visible light can result in the formation and accumulation of metabolic by-products in the retinal pigment epithelium (RPE), a pigment layer underneath the retina that normally helps remove metabolic by-products from the retina. Excess accumulation of these metabolic by-products interferes with the normal metabolic activity of the RPE and can lead to the formation of drusen.
    • Most do not progress beyond the atrophic/nonexudative stage; however, those who do are at a greater risk for severe visual loss.
  • nAMD
    • nAMD stage generally arises from the atrophic stage.
      • In type 1 neovascularization, breaks in Bruch’s membrane allow choroidal neovascular membranes (CNVMs) to grow into the sub-RPE space. This corresponds to occult CNVMs. Fluid leakage and bleeding can produce a vascularized serous or fibrovascular RPE detachment.
      • In type 2 neovascularization, the CNVM passes through the RPE and is located in the subretinal space. Typically appears as a lacy or gray-green lesion. This corresponds to classic CNVM.
      • Type 3 neovascularization, also known as retinal angiomatous proliferations (RAPS), the neovascularization develops from the deep capillary plexus of the retina and grows downward toward the RPE.
      • Polypoidal choroidal vasculopathy (PCV) is a subtype of nAMD and often presents with multiple, recurrent serosanguineous RPE detachments. An RPE detachment is also known as a pigment epithelial detachment (PED). Optical coherence tomography (OCT) features of PCV include multiple PEDs, sharply peaked PED, notched or multilobulated PED, and a hyperreflective ring surrounding an internal hyporeflective lumen beneath a PED.


  • Genetic susceptibility may be a factor in AMD: ~25% genetically determined.
  • Complement factor H Y402H genotype is an important susceptibility gene for AMD.
  • Although the development of AMD may be predicted by specific alleles, the clinical response to anti–vascular endothelial growth factor (anti-VEGF) is not.

Risk Factors

  • Obesity
  • Cigarette smoking
  • Chlamydia pneumoniae infection
  • Family history
  • Excess sunlight exposure
  • Blue or light iris color
  • Hyperopia
  • Short stature
  • High plasma high-density lipoprotein cholesterol levels are associated with an increased risk for AMD.
  • Physical activity is associated with lower risk of early and late AMD in white populations.

General Prevention

  • Ultraviolet (UV) protection for eyes
  • Routine ophthalmologic visits
    • Every 2 to 4 years for patients age 40 to 64 years
    • Every 1 to 2 years after age 65 years

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