Nearly three-quarters of cases of one of the world's most common causes of blindness are linked to just two genes, research suggests.
AMD often affects older people
Age-related macular degeneration (AMD) causes blindness in millions of older people across the globe.
A team led by New York's Columbia University hope their work could help aid the development of new treatments for the condition.
Details are published in the journal Nature Genetics.
AMD is marked by a progressive loss of central vision due to degeneration of the macula - a region of the retina responsible for fine, central vision.
Previous work had shown that several variants of a gene called Factor H significantly increase the risk of AMD.
Factor H controls production of a protein that helps shut down the body's immune response to infection once it has been successfully fought off.
People with these inherited variants of Factor H are less able to control inflammation caused by infectious triggers, which may spark AMD in later life.
However, the previous research found that about one in three people with a risky variant of Factor H had not been diagnosed with AMD.
The latest research focused not only on Factor H, but on other genes that play a role in the same immune response pathway.
A genetic analysis of 1,300 people quickly identified a second gene, Factor B, as playing a significant role.
While Factor H is an inhibitor of the immune response to infection, Factor B is an activator.
Because of the complementary roles of the these two genes, a protective Factor B variation can protect against AMD, even if one carries a risk-increasing variant of Factor H, and vice versa.
The researchers found 74% of the people with AMD had either the Factor H or Factor B risk factor or both - but no protective variants of either gene.
Lead researcher Dr Rando Allikmets said "I am not aware of any other complex disorder where nearly 75% of genetic causality has been identified.
"These findings are significant because they absolutely confirm the roles of these two genes and, consequently, the central role of a specific immune response pathway, in the development of AMD.
"In just a few short years, we've gone from knowing very little about what causes AMD to knowing quite a lot. We now have clear targets for early therapeutic intervention."
The researchers are now searching for the specific triggers that set off the immune response, and subsequent inflammation.
A spokesperson for the UK Macular Disease Society described the research as "interesting".
"It is a very useful part of the jigsaw, but only one small piece. We estimate that it will take seven to 10 years before see any cure for AMD."