Geographic Atrophy (GA) is an advanced form of dry Age-Related Macular Degeneration (AMD) that causes a progressive, irreversible loss of central vision. This condition is characterized by the death of photoreceptors and the underlying retinal pigment epithelium (RPE) cells in the macula, creating a well-defined area of atrophy. The primary concern for individuals with GA is the speed at which these atrophic lesions enlarge, as a faster rate of progression directly correlates with a more rapid decline in functional vision. Understanding the variables that influence this rate of enlargement is fundamental to managing the disease and evaluating potential treatments.
Measuring Geographic Atrophy Progression
The progression of Geographic Atrophy is tracked and quantified in clinical settings using advanced imaging technologies to monitor the expansion of the atrophic lesion area. The gold standard for visualizing and measuring GA is Fundus Autofluorescence (FAF) imaging. FAF works by detecting the natural fluorescence of lipofuscin, a metabolic byproduct that accumulates in the RPE cells; the atrophic areas appear dark (hypoautofluorescent) due to the loss of these RPE cells.
This imaging allows clinicians and researchers to clearly delineate the boundaries of the non-functional tissue. The standard unit of measurement for tracking progression is the change in the total atrophic area over time, typically expressed in square millimeters per year (mm²/year). The area-based progression rate is a widely accepted endpoint in clinical trials for assessing the effectiveness of new therapies.
Typical Rates of Atrophy Enlargement
The speed at which Geographic Atrophy lesions enlarge shows high variability among individuals, but studies have established a general range for the average rate of progression. Overall, GA progression rates reported in the literature typically range from approximately 0.5 square millimeters per year (mm²/year) to 2.6 mm²/year. A frequently cited mean or median annual growth rate falls around 1.59 mm²/year to 1.78 mm²/year.
This progression is non-linear and highly patient-specific, meaning a single average rate does not fully capture the disease’s course for any one person. Some individuals are classified as “rapid progressors,” experiencing faster enlargement, while others are “slow progressors” who maintain a slower rate over time. Progression rate is often consistent within an individual.
A faster rate of enlargement means the atrophic area reaches the center of the macula, the fovea, more quickly, leading to a more rapid decline in sharp central vision. For instance, one study found that the enlargement rate varied widely, from as low as 0.02 mm² per year up to 4.05 mm² per year. Eyes with incident GA may show a slightly faster rate of enlargement compared to those with longer-standing GA.
Patient and Ocular Factors Driving Progression Speed
Atrophy enlargement rates are influenced by specific characteristics of the lesion and broader patient factors. Characteristics of the GA lesion itself are strong predictors of progression speed. For example, a larger initial size of the atrophic area is generally associated with a higher rate of enlargement. Lesions that are multifocal (multiple distinct patches of atrophy) tend to progress more quickly than a single, unifocal lesion.
The location of the lesion relative to the fovea, the macula’s center, also plays a role in progression and functional vision loss. Lesions located closer to the fovea, or those that have already involved the fovea, tend to result in faster vision decline. Additionally, certain patterns of hyper-autofluorescence observed on FAF imaging, such as a “banded” or “diffuse” pattern at the border of the atrophy, indicate a higher risk of faster progression.
The status of the fellow eye is also a significant prognostic factor. If the other eye already has advanced AMD, progression in the affected eye is often faster. Genetic factors, specifically variations in genes related to the complement system like ARMS2 and C3, have been shown to independently influence the speed of GA lesion growth. Lifestyle factors, such as a history of smoking, are also recognized as contributing to a higher risk of progression.
Current and Emerging Treatments Aimed at Slowing Progression
For many years, no treatments existed that could slow the expansion of Geographic Atrophy, but recent advancements focusing on the complement cascade have led to approved therapies. The complement system, a part of the immune response, is thought to be overactive in AMD and contributes to the destruction of retinal cells. Current treatments are designed to inhibit this overactivity through regular injections into the eye.
Two notable complement inhibitors are pegcetacoplan (a C3 inhibitor) and avacincaptad pegol (a C5 inhibitor), both of which have demonstrated the ability to modify the rate of atrophy enlargement. Pegcetacoplan was shown to slow GA growth by approximately 19% to 22% with monthly treatment over two years compared to no treatment. Avacincaptad pegol reduced the mean GA growth rate by about 14% to 30% in clinical trials depending on the dose and duration.
These treatments do not restore vision that has already been lost, but they function by decreasing the annual rate at which the atrophic lesions grow. By slowing the lesion expansion, the goal is to delay the progression to severe vision loss and preserve vision for a longer period. While complement inhibitors are the most direct intervention, general eye health measures, such as taking specific dietary supplements like AREDS2 vitamins, can help reduce the overall risk of advanced AMD.