Description

• 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)

Epidemiology

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

Incidence

• 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.

Prevalence
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.

Genetics

• 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