Age-related Macular Degeneration
AMD is the leading cause of irreversible blindness in people over 60 years of age in the developed world. It is caused by degeneration of the macula, the region of the retina responsible for central vision. AMD is unique in that it is a common disease that has recently been linked to common variations in a few specific genes, presenting opportunities to develop both diagnostic tests and disease-modifying treatments. It is estimated that there are 15-20 million people with AMD in the U.S. and more than 50 million worldwide.
Diagram of a bisected human eye depicting the location of the macula, the region of the eye responsible for detailed, central vision [Credit: National Eye Institute, National Institutes of Health].
The early stage of AMD (often referred to as ‘dry’ AMD) is followed by one of two advanced forms of the disease. These are referred to as ‘wet’ (‘neovascular’ or ‘exudative’) AMD and geographic atrophy. Ninety percent (90%) of people with AMD have the early stage form.
The early stage of AMD occurs when drusen are deposited within the macula area. As the disease progresses, pigment disturbances follow, eventually resulting in late AMD which is associated with vision loss. These changes are readily visible by the healthcare professional during a regular retinal exam.
Retina showing drusen formation typical of dry AMD [Credit: National Eye Institute, National Institutes of Health].
Drawing of retina showing extra-cellular drusen deposit separating choroid from RPE layer behind retina. [Illustrator: Chris Gralapp, MA, CMI]
AMD can be subdivided into clinical stages, all of which may occur in one or both eyes and result in various degrees of visual deterioration.
The Clinical Age-Related Maculopathy Staging System [Seddon et al, 2006] is as follows:
- Grade 1: No drusen or <10 small drusen without pigment abnormalities
- Grade 2: Approximately ≥10 small drusen or <15 intermediate drusen, or pigment abnormalities associated with age related maculopathy
- Grade 3: Approximately ≥15 intermediate drusen or any large drusen
- Grade 4: Geographic atrophy with involvement of the macular center, or noncentral geographic atrophy at least 350 µm in size
- Grade 5: Exudative (‘wet’) AMD
[Credit: National Eye Institute, National Institutes of Health].
Wet AMD develops in approximately 10-15% of individuals with early stage (‘dry’) AMD. It occurs when new blood vessels from behind the retina grow into the macula. These new blood vessels leak blood and fluid, often elevating the macula and leading to retinal death and scarring which results in blindness.
Retina showing typical blood vessel formation and leakage in wet AMD [Credit: National Eye Institute, National Institutes of Health]
Drawing of retina showing growth of choroidal neovessels into the sub-RPE and sub-retinal regions. [Illustrator: Chris Gralapp, MA, CMI]
A number of factors have been identified that significantly increase one’s risk for developing AMD. These include:
- Genetics and family history: A significant body of research has recently implicated specific variations in a few genes to AMD. Those with immediate family members who have AMD are at a higher risk of developing the disease.
- Smoking: Smoking increases the risk of AMD.
- Obesity: Research studies suggest a link between obesity and the progression of early and intermediate stage AMD to advanced AMD.
- Race: Caucasians are much more likely to lose vision from AMD than African Americans.
- Gender: Women appear to be at greater risk than men.