Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide, with a global prevalence that is predicted to substantially increase. Identifying early biomarkers indicative of progression risk will improve our ability to assess which patients are at greatest risk of progressing from intermediate AMD (iAMD) to vision-threatening late-stage AMD. This is key to ensuring individualized management and timely intervention before substantial structural damage. Some structural biomarkers suggestive of AMD progression risk are well established, such as changes seen on color fundus photography and more recently optical coherence tomography (drusen volume, pigmentary abnormalities). Emerging biomarkers identified through multimodal imaging, including reticular pseudodrusen, hyperreflective foci, and drusen sub-phenotypes, are being intensively explored as risk factors for progression towards late-stage disease. Other structural biomarkers merit further research, such as ellipsoid zone reflectivity and choriocapillaris flow features. The measures of visual function that best detect change in iAMD and correlate with risk of progression remain under intense investigation, with tests such as dark adaptometry and cone-specific contrast tests being explored. Evidence on blood and plasma markers is preliminary, but there are indications that changes in levels of C-reactive protein and high-density lipoprotein cholesterol may be used to stratify patients and predict risk. With further research, some of these biomarkers may be used to monitor progression. Emerging artificial intelligence methods may help evaluate and validate these biomarkers; however, until we have large and well-curated longitudinal data sets, using artificial intelligence effectively to inform clinical trial design and detect outcomes will remain challenging. This is an exciting area of intense research, and further work is needed to establish the most promising biomarkers for disease progression and their use in clinical care and future trials. Ultimately, a multimodal approach may yield the most accurate means of monitoring and predicting future progression towards vision-threatening, late-stage AMD. Age-related macular degeneration, or AMD, is an eye disease that causes vision loss. Worldwide, the number of people with AMD is increasing. It is difficult for doctors to know who, among those with AMD, will get worse and lose some of their sight, and who will not. Researchers are trying to find early signs that predict whether AMD will get worse and ways to track AMD progression over time. These signs are known as "biomarkers." They can be structural (seen in the structures inside the eye), functional (a change in how well someone sees), genetic, or proteins found in the blood. Being able to identify people with AMD that are most at risk of losing their vision will help to make sure they get more frequent review so that interventions can be started quickly before vision is lost permanently. Some structural and functional biomarkers are already well known, while others may be useful and are being intensively researched. Changes in the blood markers need much more research to be useful. Researchers are also looking at how to combine data from different biomarkers. This may be a better way to follow worsening of AMD over time compared to using a single biomarker. In the future, we may also be able to use artificial intelligence to help combine all biomarker data. This is an exciting area of research that will be important to help improve the vision outcomes for people with AMD.