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 light-sensing cells and their underlying support layers in the macula, creating distinct atrophic lesions. The primary concern for people with GA is the unpredictable timing of vision loss, which is tied to the speed at which these lesions expand. Understanding how this progression is measured and what factors influence its rate is crucial for managing the condition.
Defining and Measuring the Progression of Geographic Atrophy
Medical professionals quantify GA progression by tracking the expansion of the damaged area, rather than monitoring a decline in visual acuity. Progression is defined as the increase in the total surface area of the atrophic lesion over time, typically expressed in square millimeters per year (mm²/year).
The primary clinical tools used to track this expansion are Fundus Autofluorescence (FAF) and Optical Coherence Tomography (OCT). FAF imaging highlights the health of the retinal pigment epithelium (RPE) cells, showing lesions as sharply demarcated dark patches due to the absence of pigment. OCT provides cross-sectional, high-resolution images of the retinal layers, allowing precise quantification of areas where the RPE and photoreceptors have been completely lost, known as complete retinal pigment epithelium and outer retinal atrophy (cRORA).
These imaging modalities enable doctors to accurately measure the lesion’s total area at different time points. Comparing these measurements allows the calculation of the annualized rate of expansion, providing an objective measure of disease progression. This quantitative approach is fundamental for monitoring the condition and evaluating treatment effectiveness in clinical trials.
Understanding the Average Rate of Progression
The speed at which geographic atrophy progresses varies significantly among individuals, making a specific timeline challenging to predict. Clinical studies have established an average rate of lesion enlargement, with the pooled mean growth rate reported in major meta-analyses being around 1.66 mm² per year.
Mean enlargement rates range broadly, from 1.2 mm² per year up to 2.6 mm² per year, highlighting the variability in the disease course. Progression is non-linear, meaning lesions may expand slowly for a period and then accelerate, leading to the classification of “fast progressors” and “slow progressors.”
A more consistent measure used in research is the rate of change in the square root of the lesion area, which is less dependent on the initial lesion size. The most significant impact on vision occurs when atrophic lesions reach the fovea, the center of the macula, which can happen within a median time of 1.4 to 2.5 years once the atrophy is near that area.
Biological and Lifestyle Factors That Influence Progression Speed
Progression speed is influenced by factors related to the lesion itself, the eye’s condition, and systemic patient health. The initial size of the atrophy is a strong predictor of faster progression; larger lesions expand quicker than smaller ones. Additionally, eyes with multiple small lesions (multifocal) often show higher growth rates than those with a single lesion (unifocal).
The location of the atrophy relative to the fovea, the central point of sharpest vision, is important. While extra-foveal lesions may initially progress faster in terms of area, their approach to the fovea signals an immediate threat to central vision. The presence of specific imaging features, such as subretinal drusenoid deposits, is also associated with accelerated GA growth.
Lifestyle and genetic factors contribute to the disease trajectory. Smoking is a modifiable risk factor linked to a faster rate of GA growth. Genetic markers, particularly variations in complement system genes like ARMS2 and C3, influence the speed of lesion expansion. Having GA in both eyes also indicates a more rapid or severe disease course.
Current Treatment Options Focused on Slowing Atrophy
Until recently, no treatments were available to directly slow GA progression. Current therapeutic strategies focus on modifying the disease course by targeting the complement system, a part of the immune response implicated in GA development. The first FDA-approved treatments are complement inhibitors delivered via intravitreal injection.
These treatments, including pegcetacoplan and avacincaptad pegol, inhibit different components of the complement cascade, specifically C3 and C5. Clinical trials show these agents reduce the rate of GA lesion growth compared to a sham injection. The goal is not to restore lost vision but to slow the rate of expansion, delaying the time until atrophy affects the fovea and preserving vision longer.
Pegcetacoplan, for instance, has been shown to decrease the growth of GA lesions by about 17% to 22% over a two-year period in clinical studies. Supportive measures are also important, including regular monitoring by an eye care specialist and adopting healthier habits, such as smoking cessation and dietary adjustments. These actions complement medical treatment by addressing modifiable risk factors.