Macular Degeneration, Age-Related - AMD

Macular Degeneration, Age-Related - AMD

 

Age-related macular degeneration (AMD) is a degenerative retinal disease resulting in progressive central vision loss.

Epidemiology

  • Prevalence
    • 1.6% at 52-64 years
    • 11% at 65-74 years
    • 28% at >74 years
  • Age – peaks after 65 years
  • Sex – F>M
  • Ethnicity – highest risk in Caucasians

Inheritance

  • Usually multifactorial
  • Two independent single nucleotide polymorphisms (SNP), Y402H and SNP rs10490924, are associated with an increased risk for AMD
  • Y402H is in the Complement H Factor (CHF) gene where histidine is substituted for lysine (c.1277C>T; p.Y402H)
  • The SNP rs10490924 on chromosome 10q26 has recently been found in linkage disequilibrium with an SNP rs11200638 located in the heat shock serine protease (HTRA1) gene’s promoter.  HTRA1 is believed to be the responsible functional gene for the SNP rs10490924 associated with increased risks for both types of AMD, particularly wet AMD
  • Heterozygosity for either the SNP rs10490924 or Y402H predicts a 2.8-fold (95%Cl: 2.5-3.3) and a twofold (95%Cl: 2.0-2.6) increased risk for AMD progression, respectively
  • Heterozygosity for both Y402H and the SNP rs10490924 is reported to cause a 5.8-fold (95%Cl: 4.4-7.7) increased risk for AMD progression
  • Homozygosity for either the SNP rs10490924 or Y402H increases the risk for AMD progression by 8.1-fold (95%Cl: 6.0-10.9) and 7.1-fold (95%Cl: 5.3-9.5) respectively
  • Homozygosity for both Y402H and the SNP rs10490924 predicts a 57-fold (95%Cl: 37.2-89.0) increased risk for AMD progression

Risk Factors

  • Cardiovascular disease
  • Genetics – increased risk with Y402H and SNP rs10490924
  • Female sex
  • Low socioeconomic status
  • Older age
  • Sunlight exposure
  • Tobacco use

Pathophysiology

  • Dry AMD (90%)
    • Drusen (fatty waste products of photoreceptor cells) accumulates within the retinal pigment beneath the macula
  • Wet AMD (10%)
    • Abnormal vessel growth beneath the macula, leaking blood and fluid into the macula

Clinical Presentation

  • Central vision blurring
  • Blind spots
  • Contralateral eye likely to be affected at some point

Diagnosis

  • Retinal examination
  • Genetic testing may predict likelihood of disease progression in patients with AMD or predict risk in family members

Treatment

  • Anti-VEGF therapies
  • Wet AMD – photocoagulation