AMD Progression and Prognosis

Will you lose your vision?

 

What is AMD?

Age-related Macular Degeneration (AMD) is the leading cause of irreversible vision loss and blindness in older adults in the developed world.  AMD is a progressive late onset disease of the macula, which is made up of millions of light-sensing cells that provide sharp, central vision. In its early and intermediate forms, the disease presents as small deposits on the retina comprised of cholesterol and complement (inflammatory) proteins and/or pigmentation changes in the retina. As many as 90% of individuals who live through their 70s and into their 80s will have these changes in their retina. Approximately 20% of those who develop the early and intermediate form of AMD will progress to advanced disease with vision loss as they age. With the presence of advanced stage disease, the center field of view may appear blurry, distorted, or dark. The advanced form may be dry geographic atrophy (30% of advanced disease) or wet choroidal neovascularization (70% of advanced disease)[1].

What Causes AMD

Confirmed risk factors for developing advanced AMD include age, smoking, BMI and family history. Genetic inheritance explains as much as 71% of the cause of AMD and this inheritance includes at least 12 genes that are associated with AMD progression. These genes are involved with complement immunity and inflammation, oxygen metabolism, cholesterol metabolism and genes involved in the stability of blood vessels and other tissues.

Only about 15% to 20% of people with early or intermediate Dry AMD will progress to advanced AMD with vision loss. The progression of AMD is difficult to predict in any given patient because there are a number of factors that contribute to the risk of development and progression of this disease. Some risk factors can be controlled, such as diet, smoking habits and body mass index (BMI). Other factors are fixed, such as age, gender, and family history (genotype).

Early Detection Can Save Vision

Vision can be saved if AMD is detected at an early stage. However, most people don’t know they are at an increased risk and don’t go to an eye care professional until the symptoms worsen and disease is advanced in one eye. It is then is too late to save the first eye other than perhaps preventing further vision loss through treatment with eye injections. The most important effort is then directed towards saving the second eye.

Patients with the highest genetic risk will progress approximately 12 years earlier and they should be monitored by their eye doctor much more frequently to catch the disease as early as possible[2].

 

Macula Risk Prognostic Test - Clinical Validity

Clinical validity defines a test’s ability to detect or predict the associated clinical disorder. Multiple studies have been published that demonstrate the association between Macula Risk PGx genes and risk of AMD progression, as well as patient outcomes after different treatments.

Researchers around the world have compared the ability of genetic testing to improve on the clinical eye examination by a trained eye care professional. In 2009, Seddon et al assessed an algorithm including 5 genes and the clinical eye examination [3]. These researchers demonstrated that the addition of genetics was a statistically significant improvement (P<0.001) for the prognostic assessment of AMD patients. That algorithm was 82% accurate. These researchers continued to improve their algorithm and in 2012 they developed a method that included 12 genes with the clinical eye examination to a 10-year accuracy of 89.5% and a 5-year accuracy of 88.3% [4]. That algorithm is now provided as the Macula Risk test.

Why Do We Want To Know?

You want to know if you are at risk so your eye care professional can work to save your vision. AMD can be arrested if it is detected and treated early.

In summary, Macula Risk PGx has been shown to have a 10-year predictive accuracy of 89.5%, with a sensitivity and specificity both > 80%.[4,6]  High-risk patients should be included in a disease management program in an effort to prevent progression. This may include, eye vitamins with or without zinc, smoking cessation, weight loss, increased monitoring and early treatment of wet AMD with VEGF inhibitors.

Macular degeneration is a costly disease for both the family and the healthcare system. Effective therapies are most cost effective if they are personalized for the patient and provided at the earliest detection of the developing disease.