Geographic Atrophy (GA) represents an advanced stage of dry age-related macular degeneration (AMD), a prevalent cause of vision loss among older adults. This progressive eye condition leads to irreversible degeneration of retinal cells in the macula, responsible for sharp, central vision. To better understand and manage GA, scientists and clinicians rely on biomarkers. These measurable indicators reflect a biological state or process, offering valuable insights into disease presence, activity, and response to treatment.
Understanding Geographic Atrophy and Its Progression
Geographic Atrophy directly impacts central vision by causing the loss of photoreceptors and retinal pigment epithelium (RPE) cells in the macula. This damage also extends to the underlying choriocapillaris, a network of blood vessels that supplies the RPE and photoreceptors. The disease begins with smaller, isolated patches of atrophy, often in the perifoveal region, the area surrounding the fovea.
Over time, these initial areas of atrophy gradually expand and merge, forming larger, more defined lesions that resemble islands on a map. This expansion can eventually involve the fovea, leading to significant and irreversible central vision loss, making it difficult to perform tasks like reading or recognizing faces. While the progression rate of GA varies, it is a slow but continuous process, averaging 1.43 mm² per year.
The Significance of Biomarkers in Geographic Atrophy
Biomarkers hold significant importance in understanding and managing Geographic Atrophy. They allow for GA identification before substantial vision loss, which is beneficial since visual acuity alone can be a poor indicator, especially when the fovea is spared. Tracking disease advancement also allows clinicians to monitor how quickly atrophic lesions are growing.
Biomarkers can help predict how the disease might evolve, predicting future vision outcomes. This predictive capability guides treatment decisions, informing which therapies might be most effective for specific patients. In the realm of drug development, biomarkers serve as measurable endpoints in clinical trials, accelerating the evaluation of new treatments designed to slow or halt GA progression.
Categories of Geographic Atrophy Biomarkers
Biomarkers for Geographic Atrophy can be broadly categorized into imaging, genetic, and fluid-based types. Imaging biomarkers are widely used for visualizing structural changes in the retina. Fundus Autofluorescence (FAF) imaging, for instance, detects changes in lipofuscin, a byproduct of RPE metabolism, and shows areas of RPE atrophy as sharply demarcated regions of decreased signal intensity.
Optical Coherence Tomography (OCT) is a standard for atrophy diagnosis, providing high-resolution, cross-sectional images of the macula, revealing the loss of retinal layers, RPE, and underlying choroidal thinning. OCT can identify early atrophic processes, and new terminology (iRORA and cRORA) describes these changes. Near-Infrared Reflectance (NIR) imaging, often used in conjunction with FAF and OCT, provides additional structural details of the retina.
Genetic biomarkers involve identifying specific gene variations that increase an individual’s susceptibility to GA or influence its progression. Genes associated with the complement pathway, such as CFH (Complement Factor H) and C3 (Complement Component 3), are well-known risk factors for AMD, including GA. Another gene, ARMS2 (Age-Related Maculopathy Susceptibility 2), is also strongly linked to GA risk. While these genetic variations confer a higher risk for developing GA, studies suggest they may not directly influence the rate of disease progression once GA has already developed.
Fluid-based biomarkers, less common in clinical practice, show promise in research settings. These biomarkers are found in blood or aqueous humor, the fluid in the front of the eye. Research has identified proteins like SMOC2 and IL-6 as potential biomarkers in aqueous humor that are differentially elevated in individuals with GA, suggesting their involvement in the disease’s pathophysiology. These markers can include inflammatory, complement pathway, or lipid markers, reflecting systemic or localized biological processes.
Applying Biomarkers for Diagnosis and Monitoring
The application of biomarkers in Geographic Atrophy is transforming how the disease is diagnosed and monitored, offering a more precise approach to patient care and research. Imaging biomarkers, particularly FAF and OCT, are fundamental in confirming a GA diagnosis and tracking its progression. FAF images help delineate the extent of RPE atrophy, which appears as areas of reduced autofluorescence, while OCT provides detailed cross-sectional views of retinal layer loss and choroidal changes.
A combination of different biomarker types provides a more comprehensive understanding of the disease in an individual. For instance, while imaging reveals the anatomical changes, genetic testing can identify an individual’s predisposition to GA, and fluid-based biomarkers may offer insights into the underlying inflammatory processes. These insights assist clinicians in making informed decisions regarding patient management, including determining eligibility for clinical trials involving emerging therapies to slow GA progression. The ability to objectively measure disease activity and response to treatment through biomarkers is accelerating the development of new interventions.