Kreissig lecture highlights complex role of genetics and environment in AMD

There has been marked progress over the past few decades in understanding the environmental and genetic underpinnings of age-related macular degeneration (AMD), which has formed the scientific basis for the preventive management of the disease, according to Johanna M. Seddon MD, ScM who delivered the annual Kreissig Lecture at the 14th EURETINA Congress. 

“We have seen a major evolution in thinking from the time when everyone used to say that there is no evidence that AMD is a genetic disease to the recognition today that we are dealing with a disease with genetic, nutritional and other environmental components. We now know that there are susceptible genotypes for AMD and the manifestation of disease may be modified by our behaviours and our lifestyle,” she said.

Age-related macular degeneration (AMD) is a common cause of irreversible visual loss and the disease burden is rising world-wide as the population ages, said Dr Seddon, Professor of Ophthalmology at Tufts University School of Medicine Founding Director of the Ophthalmic Epidemiology and Genetics Service of Tufts Medical Center, New England Eye Center, Boston, United States.

While genetic factors lead to various levels of susceptibility for the development of AMD, the environment modifies the effects of this predisposition to varying degrees depending on the level of genetic risk, she explained. 

With this in mind, she noted that genotyping may become a useful tool for identifying individuals who are at high risk for disease and who may therefore benefit from increased surveillance and personalized treatment strategies. 

Reviewing the sea-change in thinking that has taken place over the past decade or so, Dr Seddon said that numerous scientific publications now attest to the fact that both environmental and genetic factors contribute to the development of AMD. 

Among environmental factors, Dr Seddon identified smoking, obesity and dietary factors, including antioxidants and dietary fat intake which have been shown to influence the onset and progression of AMD. 

Dr Seddon and co-workers were the first to carry out a systematic study of diet and AMD, and discovered the beneficial impact of dietary lutein and zeaxanthin as well as omega-3 fatty acids on AMD.

There are also several lines of evidence linking cardiovascular, immune and inflammatory biomarkers to AMD, said Dr Seddon. Genome-wide association studies have revealed numerous common variants associated with AMD and sequencing is increasing knowledge of how rare genetic variants strongly impact disease. 

“While the evidence for interactions between environmental, therapeutic and genetic factors is emerging, elucidating the actual mechanisms of this interplay remains a major challenge in the field,” said Dr Seddon.

More than 20 common and rare AMD genetic loci have been confirmed, gene-environment and gene treatment interactions are emerging, and both the genetic and lifestyle risk factors point to a central role for the inflammatory, immune, lipid, collagen extracellular matrix degradation, and angiogenic pathways in AMD, she said. 

Summing up, Dr Seddon said that the knowledge of non-genetic, modifiable risk factors along with information about heritability and genetic risk variants for this disease acquired over the past 25 years have greatly improved patient management and the ability of clinicians to predict which patients will develop or progress to advanced forms of AMD. Personalized medicine and individualized prevention and treatment strategies may become a reality in the near future, she said. 

Dr Seddon finished her lecture by paying tribute to the work of Professor Ingrid Kreissig for her immense contribution to ophthalmic training and research, particularly in the field of retina.