Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) refers to the degeneration of the macula, the central part of the retina.

AMD is classified into two types:

  • Nonexudative (dry/atrophic) AMD
  • Exudative (wet) AMD

AMD is a common condition and is one of the primary causes of adult blindness. Over 170 million people are affected, and the number is expected to grow. Dry AMD affects more people than wet AMD, but is less severe and may progress to wet AMD. 

What causes AMD?

Age-related macular degeneration is thought to result from aninterplay of genetics, inflammation, and external risk factors. 

The development of dry AMD has not been completely understood but has been found to involve decreased perfusion of the Bruch’s membrane, inflammation and activation of the immune system, atrophy of the retinal pigmented epithelium (RPE), and deposition of fatty extracellular material called drusen. 

The etiology of wet AMD is based on the inflammatory response triggered by drusen deposition and loss of RPE that leads to an increase in vascular endothelial growth factors (VEGF). The increase in VEGF and dysregulation of the immune response give rise to choroidal neovascularization, the growth of abnormal vessels under the retina. Leaking from these vessels consequently creates deposition of subretinal fluid or hemorrhages in the subretinal space.

Several polymorphisms of the complement factor H (CFH) gene and other genes involved in the complement pathway have been implicated in the development of AMD through the increase of inflammation and induction of apoptosis of the RPE cells. 

Besides genetics and positive family history, there is evidence of other risk factors in the development of AMD:

    • Age– The prevalence of AMD increases with increasing age, affecting 24% of people aged 65 to 74 and over  44% of people aged 70 to 95.
    • Gender– Women have a higher risk for exudative AMD.
    • Ethnicity– Caucasians are at a higher risk of developing AMD than other ethnicities, however, the incidence of dry AMD is increasing in Asian populations.
  • Smoking- Increases risk of wet and dry AMD, and is associated with early disease progression and involvement of both eyes.
  • Chronic medical conditions-  Cardiovascular diseases (hypertension, stroke, MI), AIDS, neurodegenerative diseases (Parkison’s disease, Alzheimer’s disease)
  • Alcohol use
  • Diet- Increased risk in those with a diet high in fat and trans-fats. 
  • Blue light exposure

Symptoms of AMD

Symptoms of dry AMD can be insidious with a gradual loss of central vision that may occur over many years. Patients may complain of difficulty in low light conditions or trouble with adapting to changes in light intensity. Distortion of vision may occur and worsen over the years. Advanced stages of the disease can result in a late atrophic form with degeneration of the retinal layers or may progress to wet AMD.  Fundoscopic examination often reveals the presence of drusen which may increase as the disease progresses. 

Wet AMD may not present with symptoms at early stages, and may appear gradually or with acute changes. Patients often notice changes in vision which may include loss of central visual acuity, abnormalities in discerning color and contrast, or distorted vision. 

Treatment of AMD

The destruction of the retinal cells is irreversible and there is currently no cure for AMD and no approved pharmacological treatment for dry AMD. There is some evidence that supplementation of Vitamins C and E, beta-carotene, and Zinc may slow the progression of dry AMD to wet AMD. Making lifestyle changes such as smoking cessation and improving blood pressure control can decrease the risk of advancement of disease.

The progression of wet AMD may also be staved off by lifestyle modifications and supplementation of antioxidant vitamins and zinc. Preventing further neovascularization can be achieved by the use of several modalities:

  • Intravitreal VEGF inhibitors (eg: Afilbercept, ranibizumab)
  • Photodynamic therapy (PTD)
  • Thermal laser photocoagulation
  • Radiation therapy

Source: Fernandes, A. R., Zielińska, A., Sanchez-Lopez, E., dos Santos, T., Garcia, M. L., Silva, A. M., Karczewski, J., & Souto, E. B. (2022). Exudative versus Nonexudative Age-Related Macular Degeneration: Physiopathology and Treatment Options. International Journal of Molecular Sciences, 23(5), 2592.