Causes and Risk Factors of Geographic Atrophy

Geographic atrophy occurs in the late stage of age-related macular degeneration (AMD). It is linked to several risk factors including advanced age, family history, and cigarette smoking.

This article will cover the most common risk factors for geographic atrophy, the role of genetics and lifestyle, as well as how these factors may make you more vulnerable to the condition.

Common Causes

Researchers have not been able to pinpoint the exact cause of geographic atrophy. It is understood that the cells of the area near the center of the retina (macula) begin to waste away and die, which leaves a blank spot in a person's vision. However, the precise mechanism by which this happens is unclear.

Scientists think that a variety of factors are at play. Age and family history are the most significant risk factors. If you have close relatives with a history of geographic atrophy, you might be more likely to get it.

Genetics also appears to play a role. For example, in some donor eyes with geographic atrophy, errors found in part of the immune system known as the complement cascade have been observed. If this system is not functioning correctly, inflammation can occur. In turn, the inflammation may make the eye more vulnerable to geographic atrophy.

Risk factors related to medical history include:

• Coronary heart disease or high cholesterol levels
• Having a cataract (clouding of the lens) or having undergone prior cataract surgery
• Having geographic atrophy in one eye already
• Taking thyroid hormones or antacids
  

Age

The older you are, the more likely you are to develop geographic atrophy. The condition usually affects people over the age of 60.

It's thought that cumulative damage can lead to chronic inflammation that ultimately causes the retinal cells to die. The retinal pigment epithelium does not regenerate quickly, leaving it particularly vulnerable to progressive cell loss over time.

Genetics

The genes you have might be important in determining your risk for developing geographic atrophy, and they seem to have a connection to AMD in general. However, not all cases of AMD progress to late-stage geographic atrophy.

Four genetic variations, known as single nucleotide polymorphisms (SNPs), appear to play a role in the progression of late AMD to either geographic atrophy or another late complication known as choroidal neovascularization (CNV).

In CNV, something spurs the eye to grow new—but abnormally leaky—blood vessels. With geographic atrophy, the structure of the retina begins to break down, and cells start to waste away.

Researchers have found that four SNPs seemed to be important to this process:

• CFI (rs10033900)
• CETP (rs3764261) 
• VEGFA (rs3025000)
• APOE (rs7412)

Malfunction of these SNPs may lead to the development of geographic atrophy or potentially to CNV.

Other genes are also thought to be related to geographic atrophy. For example, a gene variant called ARMS2 (rs10490924) may spur early AMD cases to become late ones as well as make the geographic atrophy lesions grow faster.

Researchers think that the gene might also be linked to the development of geographic atrophy in the second eye and causing these lesions to grow more quickly.

There could also be other genes involved in the risk of geographic atrophy that researchers have yet to identify.

Lifestyle Risk Factors

Environmental stress from several factors may make you more vulnerable to geographic atrophy, including:

• Cigarette smoke can potentially cause cumulative damage to the cells as you age. Current and former smokers are at significantly greater risk for developing geographic atrophy.
• A body mass index (BMI) of 25 or higher is associated with an increased risk for advanced AMD.

Smoking

Smoking can increase your risk of developing geographic atrophy. Chemicals that the body absorbs from smoking can travel to the retina and damage it. It's thought that cigarette smoke irritates the cells, which in turn spurs the immune system to take action and cause harmful inflammation.

The act of smoking itself also causes the immune system's complement cascade to turn on, which has been connected to AMD. This might be more harmful to some people than others, which points to a potential genetic link.

Summary

Common risk factors for geographic atrophy include smoking, older age, and a family history of the condition. While the exact genetic mechanism is not yet known, it is clear that there is a hereditary component. Having specific genes may make you more vulnerable to the condition.

Lifestyle factors such as your weight, having health conditions like heart disease or cataracts, and taking certain medications may increase your risk of geographic atrophy.

A Word From Verywell

Many factors contribute to your risk of geographic atrophy, but you might be able to lower your risk by modifying some that are in your control. While there are no guarantees, taking steps to positively change your life and health may help you head off geographic atrophy or slow the progression of the condition.