Age-related maculopathy: a product of genetics and environment?

July 15, 2005

Fort Lauderdale, FL—The phenotype of age-related macular disease provides information about the genes that confer risk or the environmental factors that are involved in risk in a particular individual, according to Alan Bird, MD, who spoke at the annual meeting of the Association for Research in Vision and Ophthalmology.

Fort Lauderdale, FL-The phenotype of age-related macular disease provides information about the genes that confer risk or the environmental factors that are involved in risk in a particular individual, according to Alan Bird, MD, who spoke at the annual meeting of the Association for Research in Vision and Ophthalmology.

"It has been thought for a long time that both inheritance and environment play a role in the pathogenesis of disease," said Dr. Bird, professor of clinical ophthalmology, Institute of Ophthalmology, London.

Individuals will develop an age-related macular disease in the presence of the appropriate genetic risk factors and appropriate environmental pressures, Dr. Bird explained. There is a great deal of evidence for genetic predisposition to age-related macular degeneration (AMD) from numerous twin and sibling studies.

Dr. Bird and his colleagues conducted a study in which they evaluated siblings and spouses of patients with AMD. The results showed good concordance between the patients and the siblings and no concordance between the spouses and the patients in number, type, and distribution.

"The genetic risk is not only the risk of having changes of AMD but also determining the qualitative attributes that age changes in early age-related maculopathy," Dr. Bird explained. Based on this, there should be symmetry between eyes, which had been proposed as long as 100 years ago. Dr. Bird and colleagues found very good concordance between two eyes of an individual in the density, number, and size of drusen; however, there was also good concordance in fluorescein characteristics.

"There seems to be symmetry between two eyes of an individual in qualitative attributes in early AMD. There is good evidence that inheritance is important," he said, but questioned why lack of concordance between patients and their spouses existed if the environment is important.

Early age-related maculopathy Enormous differences exist in early age-related maculopathy in the quantitative and qualitative aspects of phenotype, examples of which may be small fine drusen distributed widely in the retina in the posterior pole, small well-defined drusen with pigment, drusen that are largely eccentric to the foveola, and large soft drusen in the central retina that become small toward the periphery.

What is noteworthy, Dr. Bird said, is that what is in one eye is also consistently in the fellow eye. Another characteristic is that drusen in age-related maculopathy almost never fluoresce; interestingly, drusen in young patients fluoresce brightly, according to Dr. Bird, reflecting a fundamental difference between these drusen and those in elderly patients in age-related maculopathy.

In a study of late age-related macular disease, most eyes had concordance between lesions that destroy vision bilaterally, but this was not absolute.

Geographic atrophy The question arises of whether geographic atrophy is genetic or environmental. Dr. Bird noted that there is some evidence that environment is instrumental in the development of geographic atrophy because the visual loss that occurs with geographic atrophy differs widely in different locations.

In a small percentage of eyes, geographic atrophy caused visual acuity loss bilaterally. In the United Kingdom, this occurs in 20% to 25% of patients with AMD. However, in Iceland, this occurs in 80% of patients, which may reflect that the environment plays a role.

"That is derived from the observation that focal increases in autofluorescence give rise to geographic atrophy," Dr. Bird said. "Autofluorescence is influenced by life-long dietary uptake of vitamin A, which is very high in the Icelandic diet, and may influence age-related macular disease."

There are differences in phenotype in age-related macular disease in early and late stages and particularly in early disease, he said.

The phenotype reflects the disease in that individual, which may be influenced by genetic factors, environmental factors, or both. The phenotypic characterization-particularly considering qualitative rather than quantitative attributes-produces purer samples of disease that should aid genetic and epidemiologic research, according to Dr. Bird.

"Phenotype also may lead to concepts of pathogenesis," Dr. Bird concluded. "We would understand the disease better if we could understand the phenotype."