Age-related macular degeneration (AMD) is a progressive eye condition affecting the macula, the central part of the retina responsible for sharp, straight-ahead vision. The macula is densely packed with light-sensing photoreceptors, which transmit detailed visual information to the brain. Damage to this small area significantly impairs the ability to perform tasks like reading, driving, and recognizing faces, though peripheral vision usually remains unaffected. AMD is a leading cause of vision loss for older adults, with prevalence increasing substantially after age 50.
Defining Age-related Macular Degeneration (AMD)
AMD begins with structural changes underneath the retina, notably the accumulation of tiny yellow deposits called drusen, composed of lipids and proteins. The presence of drusen and corresponding pigment abnormalities characterizes the early and intermediate stages of the disease. As the condition advances, it is categorized into two primary forms: dry (non-neovascular) and wet (neovascular) AMD.
The dry form of AMD is the most common, accounting for about 90% of all cases. It involves the gradual thinning and deterioration of the macula’s layers, including the retinal pigment epithelium (RPE) and the photoreceptors. This slow breakdown of cells, known as atrophy, leads to a progressive loss of central vision over time.
Wet AMD is less common but more serious, often leading to rapid and severe vision loss. This form is defined by choroidal neovascularization, the growth of fragile, abnormal blood vessels beneath the macula. These new vessels are prone to leaking blood and fluid, causing swelling and scarring that damages the macula’s cells. While dry AMD progresses slowly, wet AMD can cause noticeable changes in vision within days or weeks.
Geographic Atrophy (GA): The Advanced Stage
Geographic Atrophy (GA) represents the late, most severe stage of dry AMD. It is characterized by the irreversible death of cells in the outer retina, including the RPE, photoreceptors, and the underlying capillaries. The term “geographic” is used because the areas of cell death appear as distinct, well-demarcated patches that resemble a map when viewed by a doctor.
This atrophy leads to the formation of permanent blind spots, or scotomas, in the central field of vision. The lesions typically start outside the very center of the macula (the fovea) and then progressively expand and coalesce over time. Once the atrophic lesions grow into the fovea, the loss of sharp central vision becomes permanent and profound.
The underlying mechanism involves chronic oxidative stress and a dysfunctional inflammatory response, particularly the overactivation of the complement system. This leads to a gradual breakdown of the RPE cells, which support the photoreceptors. The death of RPE cells starves and destroys the overlying photoreceptors, resulting in the permanent visual defect of GA.
Recognizing the Symptoms and Risk Factors
The symptoms of AMD, including progression to GA, typically affect central vision but spare peripheral sight. In the intermediate stages of dry AMD, a person may first notice difficulty seeing in dim light or a need for brighter illumination when reading. Colors may also appear less vibrant or intense.
As the condition advances, especially with the development of GA, patients may experience a gradual loss of visual sharpness and the appearance of a blurry or dark spot in the center of their vision. Another common sign is the distortion of straight lines, making objects like doorframes or utility poles appear wavy or crooked. This loss of central vision makes detailed activities like reading or recognizing faces challenging.
The strongest non-modifiable risk factor for developing AMD and GA is increasing age, with the risk rising significantly after age 60. Genetic predisposition is also a major factor, as a family history of AMD substantially increases vulnerability. Smoking is the most significant modifiable risk factor, doubling the risk and accelerating progression. Other associated factors include a diet low in certain antioxidants, obesity, high blood pressure, and cardiovascular disease.
Current Approaches to Management and Treatment
The management of AMD begins with regular eye examinations to detect the condition early, often using tools like the Amsler grid for at-home monitoring and Optical Coherence Tomography (OCT) for detailed retinal imaging. For patients with intermediate dry AMD, high-dose vitamin and mineral supplements, based on the Age-Related Eye Disease Studies (AREDS), are recommended to slow progression. These supplements contain:
- Vitamins C and E
- Zinc
- Copper
- Lutein
- Zeaxanthin
Treatment for wet AMD is well-established, relying primarily on intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs directly into the eye. These medications work by blocking the protein that causes the growth and leakage of the abnormal blood vessels, often stabilizing or improving vision. These injections are typically administered every four to twelve weeks, and they remain the standard of care for this form of the disease.
For Geographic Atrophy, the advanced stage of dry AMD, treatment options were historically limited, as anti-VEGF injections do not address the underlying atrophy. However, recent therapeutic advancements have introduced new injectable treatments that target the complement system, a part of the immune response implicated in GA progression. Medications like pegcetacoplan and avacincaptad pegol are now available to slow the growth rate of the atrophic lesions, though they cannot restore vision already lost.