Macular Degeneration, Age-Related

Age-related macular degeneration (AMD) is a degenerative retinal disease resulting in progressive central vision loss. AMD is the leading cause of blindness in older adults (>60 years) in North America and Europe.

Epidemiology

Prevalence
- 52-64 years – 1.6%
- 65-74 years – 11%
- >74 years – 28 %
Age – peak is >65 years
Sex – M<F
Ethnicity – Caucasians (highest risk)

Inheritance

Usually multifactorial
Two single nucleotide polymorphisms (SNP), Y402H and A69S, are independent risk factors for the development or progression of AMD; together, they account for approximately 70% of AMD risk
- Y402H (c.1277T>C) is in the complement H factor (CHF) gene where histidine is substituted for lysine
- A69S (c.205G>T) is located in the age-related maculopathy susceptibility 2 (ARMS2) gene, also known as LOC387715
Heterozygosity for either A69S or Y402H predicts a nearly threefold (95% Cl: 2.5-3.3) and a twofold (95% Cl: 2.0-2.6) increased risk for AMD, respectively
Heterozygosity for both Y402H and A69S is reported to cause a nearly sixfold (95% Cl: 4.4-7.7) increased risk for AMD
Homozygosity for either A69S or Y402H increases the risk for AMD by more than eightfold (95% Cl: 6.0-10.9) and more than sevenfold (95% Cl: 5.3-9.5), respectively
Homozygosity for both Y402H and A69S predicts a 57-fold (95% Cl: 37.2-89.0) increased risk for AMD

Risk Factors

Cardiovascular disease
Caucasian race
Genetics – increased risk with Y402H and A69S
Female sex
Low socioeconomic status
Older age
Sunlight exposure
Tobacco use
BMI ≥25

Pathophysiology

Dry AMD
- Early AMD
  - Spectrum of changes observed before the overt loss of vision
    - Drusen – fatty waste products of photoreceptor cells that accumulate within the retinal pigment beneath the macula, hypo- and hyperpigmentation of macula
- Late AMD
  - Neovascularization and/or geographic atrophy observed
Wet AMD
- Abnormal vessel growth beneath the macula, leaking blood and fluid into the macula

Clinical Presentation

Mild to severe visual impairment
Central vision blurring
Blind spots (scotomas)
Contralateral eye likely to be affected at some point

Treatment

Anti-VEGF (vascular endothelial growth factor) therapies
Thermal laser photocoagulation and photodynamic therapy

Indications for Testing

Macular degeneration on retinal examination

Laboratory Testing

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

Differential Diagnosis

Inflammatory eye diseases
Severe myopia

Tests generally appear in the order most useful for common clinical situations

Test name: Macular Degeneration, Age-Related, 2 DNA Markers

ARUP #: 0051674

Methodology: Polymerase Chain Reaction/Fluorescence Monitoring

Use:

Predict the likelihood of disease progression in individuals affected with early-stage AMD

Provide incentive for lifestyle modification in individuals with high-risk genotypes

Determine risk for AMD in individuals with a positive family history

Limitations:

Not recommended for nonsymptomatic patients <18 years

Detects only the two most common genetic variants associated with AMD

The variants tested are associated with risk for AMD but may not be causal for the disorder

Analytical sensitivity may be compromised by rare primer- or probe-site mutations

Follow-up:

Counseling and informed consent are recommended for genetic testing

Guidelines

General

Comprehensive Review: March 2011
Last Update: March 2011

Nicotine & Metabolites