Glaucoma genes weigh in

Key Points

Orlando, FL-Genetic research has identified genes that can cause glaucoma primarily on their own and genes that require involvement of multiple genes and environmental factors in order for the disease to develop. John H. Fingert, MD, PhD, explained the current status of genetics research in glaucoma during Glaucoma Subspecialty Day at the annual meeting of the American Academy of Ophthalmology.

"Genes are important in primary open-angle glaucoma (POAG)," said Dr. Fingert, associate professor ophthalmology and visual sciences, University of Iowa, Iowa City.

"The four classic risk factors that we all know for POAG are family history, race/ethnicity, IOP, and age," he said. "Central corneal thickness was identified more recently as a risk factor for POAG. All of these risk factors, with the exception of age, have a strong genetic basis."

The specific POAG genes have begun to be identified only recently, and their role in glaucoma pathogenesis has only begun to be investigated, Dr. Fingert noted.

"Glaucoma is heterogeneous, that is, it is probably a collection of clinically similar-appearing conditions that have a different set of genetic or multifactorial causes," he said.

In order to understand the genetic basis of the disease, Dr. Fingert noted that glaucoma can subdivided into two categories that are based on genetic contributions (i.e., POAG that results from the combined actions of many genes and environmental factors and POAG that results primarily from one gene).

Multiple gene involvement

In the first subdivision, the key feature is that each gene contributes a small risk of developing glaucoma and no single gene can cause glaucoma in isolation. These types of genes are seen commonly in individuals who do not have glaucoma in the general population but they occur at a much higher rate in patients with POAG, according to Dr. Fingert.

Six genes that contribute to the development of POAG that has a complex genetic basis were identified in 2011. Fourteen other genes that contribute to key features of POAG-such as the cup-to- disc ratio and the central corneal thickness-and to the risk of glaucoma have also been identified.

Large genetic studies are under way in the United States and elsewhere that are looking at complex genetic causes of the disease. These studies are the National Eye Institute's Glaucoma Human Genetics Collaboration, the Twin Study of Myopia and Glaucoma Risk Factors, Quantitative Traits Genome Wide Association Study of the Ocular Hypertension Treatment Study cohort, and the Gene- Environment Interactions in Glaucoma Study. The results of these trials are likely to uncover many more genetic risk factors for glaucoma that has a complex basis, according to Dr. Fingert.

Great progress has been made in the study of complex forms of genetic glaucoma. Many genetic risk factors have been discovered, he said.

"This is a complex puzzle and we are starting to obtain pieces to put the puzzle together," he said. "In the future, we may uncover enough of the genetic risk factors to allow us to predict accurately who has the highest risk of developing glaucoma. Perhaps we will be able to tailor therapies to prevent optic nerve damage before it develops. Study of the causative genes may also help in the development of therapies. There currently is no clinical utility for testing for complex genetic forms of glaucoma." However, in the future when more of the factors are discovered, testing may become more useful.