Age-Related Macular Degeneration: Causes

Pathogenesis (disease development)

Macular degeneration is a disease with progressive visual impairment. The cause of this disease is degeneration of the macula lutea (yellow spot or point of sharpest vision). In macular degeneration, the macula lutea is affected by other tissue changes besides degeneration, such as drusen (yellowish, sometimes confluent subretinal (“below the retina”) lipid deposits), which in turn limit vision. Age-related macular degeneration (AMD) can be divided into an early form, an intermediate form, and two late forms:

• “Dry” form of AMD – In this case, so-called drusen form at the back of the eye in the early stages. In the late stage, there are two-dimensional degeneration, through which the photoreceptors (light-sensitive sensory cells) perish.Course: slow, steady deterioration of central visual acuity, in the periphery, however, no changes; frequency 85-95% of cases.
• “Wet” or “exudative” AMD (synonym: neovascular AMD) – The focus is on the growth of vascular membranes from the choroid into the overlying macular retina (retina) (= choroidal neovascularization). As a result, macular hemorrhages and the formation of edema (water accumulation) in the area of the macula occur. This also leads to the loss of photoreceptors. Progression: acute deterioration of central visual acuity (“central gray haze”) and distorted vision (metamorphopsia).

In addition to the two aforementioned late forms, there is also atrophic AMD. Note: Not infrequently, mixed forms of the two late stages also occur in the same eye. Genetic risk factor for AMD is the protein factor-H (FH), which is part of a complex cascade of the immune system. In this process, FHR4 is a critical regulator of complement in the eye. Genetically higher levels of FHR4 in the blood lead to its increase in the eye, which in turn increases the risk of uncontrolled complement activation, thereby exacerbating the disease.

Etiology (Causes)

Biographic causes

• Genetic burden – if there is a family history of disease, one’s own risk is also increased
  • Genetic risk dependent on gene polymorphisms:
    • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
      • Genes: ARMS2, C2, CFH, CR, TLR3.
      • SNP: rs10490924 in the ARMS2 gene.
        • Allele constellation: GT (2.7-fold).
        • Allele constellation: TT (8.2-fold)
      • SNP: rs1061170 in the gene CFH
        • Allele constellation: CT (2.5-fold).
        • Allele constellation: CC (5.9-fold)
      • SNP: rs2230199 in gene CR
        • Allele constellation: CG (1.6-fold).
        • Allele constellation: GG (2.5-fold)
      • SNP: rs1061147 in the gene CFH
        • Allele constellation: AA (2.76-fold).
        • Allele constellation: AC (0.97-fold)
        • Allele constellation: CC (0.34-fold)
      • SNP: rs3775291 in the gene TLR3
        • Allele constellation: AG (0.71-fold for dry AMD).
        • Allele constellation: AA (0.44-fold for dry AMD)
      • SNP: rs9332739 in gene C2
        • Allele constellation: CG (0.47-fold).
        • Allele constellation: CC (0.47-fold)
      • SNP: rs547154 in gene C2
        • Allele constellation: AC (0.47-fold).
        • Allele constellation: AA (0.47-fold)
• Age – increasing age (from the age of 65).
• Skin type – heavy tanned fair-skinned with light hair and light eye color.
• People who are sensitive to bright light

Behavioral causes

• Nutrition
  • High fat consumption
  • A high dietary glycemic index is associated with an increased risk of age-related macular degeneration (AMD)
  • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
• Consumption of stimulants
  • Tobacco (smoking)
    • AMD for smokers versus nonsmokers: odds ratios between 2.6 and 4.8
    • Wet AMD occurs on average about 5 years earlier in smokers than in nonsmokers
• “Laser disco macula” as a result of damage caused by laser use in discotheques.

Disease-related causes

• Atherosclerosis (arteriosclerosis, hardening of the arteries).
• Diabetes mellitus
• Hypertension (high blood pressure)
• Infection with Chlamydia pneumoniae; HIV, chronic.
• Coronary artery disease (CAD) (disease of the coronary arteries).

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

• Elevated C-reactive protein (CRP).
• Hypercholesterolemia – high LDL cholesterol
• Hyperhomocysteinemia (> 12 mmol/l) – increased homocysteine levels.

Medication

• Acetylsalicylic acid (ASA) – regular use (more than once per week at baseline) of ASA (150 mg) increased the risk of neovascular AMD (wet AMD)

Operations

• Star surgery for light risk

Environmental pollution – intoxications (poisonings).

• Radiation exposure – intense sunlight (UV-A and UV-B).