Age-related maculopathy: A genetic and epidemiological approach

textabstractIn the 19th century, age-related maculopathy (ARM) was described for the first time as an agerelated abnormality of the macula lutea. ARM consists of a variety of clinical signs, from the early stages with soft distinct drusen, indistinct drusen and pigment alterations up to the late stages of geographic atrophy and neovascular macular degeneration. These late stages are also referred to as age-related macular degeneration. Nowadays, ARM is the leading cause of blindness among the elderly in the Western world. With the rapidly growing popUlation of the elderly, it can be estimated that in the Netherlands ahnost 115,000 people will have signs of the end stages in the year 2030. This will have great implications for the quality of life of these patients, since age-related macular degeneration decreases central vision. Furthermore, treatment is only limited to a small group of patients. Although many investigators have tried to unravel the pathogenesis of ARM, the knowledge of its etiology is still limited. Many environmental factors have been implicated as risk factors in ARM, however limited factors were consistent. While already in 1875 the first description of a genetic component in ARM was given by Hutchington and Tay/ it was only since the last decade that research on the genetic factors in ARM has gained worldwide attention. Studies on the genetics of ARM have been hampered by the lack of suitable patient material and insight in complex diseases such as ARM. The aim of this thesis is to obtain more knowledge on the disease frequency and its risk factors. Special attention is addressed to the genetic factors involved in ARM. The first part of this thesis gives an overview of the current knowledge on the genetics of ARM. In the second part the disease frequency and its risk factors are described. The third part covers two genetic-epidemiological approaches to study the genetics of ARM. The fourth part addresses two candidate genes for ARM