Serum Markers for Vascular Risk in Persons With AMD

We hypothesize that the pathogenesis of AMD includes vascular risk factors and that inflammatory markers of vascular risk in the blood may also be markers for AMD development and progression. The proposed study uses clinical data and stored blood samples from the Blue Mountain Eye Study (a population-based survey of vision and common eye diseases, including AMD, in an urban population aged 49 years or older residing in two postal code areas of the Blue Mountains region, west of Sydney, Australia).

Age-related macular degeneration (AMD) is a disease involving the central part of the retina at the back of the eye, which is responsible for accurate visual tasks such as reading. It is the leading cause of irreversible blindness in Western countries. In the USA, AMD affects at least II million individuals. It is a debilitating disease, remaining untreatable for the majority of patients, and its cause is largely unknown. It is possibly a disease involving both genetic and environmental factors. Increasing age is the most important risk factor for AMD; its risk increases exponentially with increasing age after 50 years. The socioeconomic impact of this disease is expected to increase as our population ages.

Other risk factors reported for AMD include familial risk, tobacco smoking (the strongest identified environmental risk factor for AMD), history of atherosclerotic vascular diseases such as heart attack and stroke, high blood pressure, high cholesterol level, high dietary fat intake, and obesity. In addition, other scientific studies have demonstrated components of atherosclerosis (such as inflammatory changes in the blood vessel wall) in donor eyes with AMD and in the blood of patients with the disease. AMD may, therefore, represent an atherosclerotic or inflammatory vascular disease manifest in the eye as well as the principal sites of the heart and brain.

The use of oral aspirin, an anti-inflammatory medication, in the prevention of heart attack and stroke has been established. There have been several ongoing clinical trials investigating the effects of various anti-inflammatory therapies on the development and progression of AMD. However, the level of inflammatory markers in the blood of patients with compared to those without AMD, is unknown.

Hypotheses

We hypothesize that the pathogenesis of AMD includes vascular risk factors and that inflammatory markers of vascular risk in blood may also be markers for AMD development and progression.

The Blue Mountains Eye Study (BMES) is a population-based survey of vision and common eye diseases, including AMD, in an urban population aged 2:49 years residing in two postal code areas of the Blue Mountains region, west of Sydney, Australia. The proposed study uses clinical data and stored blood samples from the BMES. We aim to assess the relationship between AMD and several inflammatory markers, including C-reactive protein, fibrinogen, intercellular adhesion molecule-I, interleukin-6, von Willebrand factor, plasminogen-activator inhibitor-I, and plasma homocysteine; the latter being potentially reversible with oral vitamin (folate) supplementation.

Goals

If our hypothesis is confirmed, it:

1. will provide further knowledge into the causes of AMD;
2. may provide new therapeutic and preventive options for AMD management (e.g., use of oral aspirin and vitamins); and
3. could eventually reduce the number of persons who are blinded by AMD.