Risk Factors for Drusen Progression

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. The etiology and pathogenesis of this disease remain largely unknown. In Europe about two million people suffer from AMD. According to the Age-Related Eye Disease Study (AREDS) the disease can be classified into early, intermediate and late. Early age-related macular degeneration is characterized by the presence of small or medium-sized drusen and/or retinal pigmentary abnormalities. Intermediate age-related macular degeneration is characterized by large drusen or numerous medium-size drusen and/or geographic atrophy not extending to the center of the macula. Late age-related macular degeneration can be either atrophic with extension to the macula or neovascular. The late form of the disease is associated with a pronounced loss of visual acuity.

In the recent years several studies focused on risk factors for late AMD and a recent systematic review and meta-analysis reported risk factors for AMD based on 16 studies in almost 114000 subjects. Strong and consistent associations with late AMD for found for increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD. Consistent associations between late AMD and higher body mass index, history of cardiovascular disease, hypertension and higher plasma fibrinogen were also found, but the association was weak. Inconsistent associations were found for gender, ethnicity, diabetes, iris color, history of cerebrovascular disease, serum total and HDL cholesterol and triglyceride levels.

Evidence has also accumulated that other factors influence the risk for AMD. Several genetic risk factors have been identified in the last years including genes in the alternative complement pathway and the RMS2/HTRA1 region. In addition, post-hoc analysis of data from the AREDS study has indicated that reduced intake of the omega-3 free fatty acids eicosapentaenoic acid and docsahexaenoic acid are associated with the risk of late AMD thereby supporting previous population based studies. The AREDS study also revealed that reduced intake of the macular pigment lutein and zeaxanthin may be associated with late AMD, again supporting previous population-based studies. Finally, 2 small studies indicate that reduced choroidal blood flow is associated with an increased risk of developing late AMD.

Less data are available for the progression of early or intermediate AMD and the associated risk factors. This is at least partially related to the problems in quantifying progression of drusen size and volume. In the recent years, however, significant efforts have been achieved in optical coherence tomography (OCT)-based methods for quantifying drusen progression and drusen volume. Polarization-sensitive OCT is the most promising of these approaches and will be used to quantify drusen area and volume in the present study.