Age-related macular degeneration (AMD) remains the leading cause of irreversible vision loss in developed countries, with its global prevalence expected to soar to 288 million by 2040. While our ability to detect the disease has been revolutionized by advanced imaging, our standard classification systems are struggling to keep pace.
A recent review in Graefe’s Archive for Clinical and Experimental Ophthalmology highlights a growing gap between the Beckman classification—the current gold standard based on color fundus photography (CFP)—and the complex clinical realities revealed by multimodal imaging.
The Limitations of a CFP-Only Approach
The Beckman system, though simple and widely used, relies on findings such as drusen size and pigmentary changes. However, it fails to account for several high-risk phenotypes that are invisible or poorly characterized on standard photography. This often leads to the misclassification of high-risk eyes as “early AMD” or their exclusion from clinical trials entirely.
Furthermore, the category of Intermediate AMD is currently treated as a uniform group, yet it encompasses a highly heterogeneous set of phenotypes with vastly different risks of progression to late-stage disease.
New Frontiers in AMD Phenotyping
Modern imaging modalities—such as Optical Coherence Tomography (OCT), OCT Angiography (OCTA), and Fundus Autofluorescence (FAF)—have identified several critical biomarkers that demand inclusion in future staging frameworks:
- Reticular Pseudodrusen (RPD): Also known as subretinal drusenoid deposits (SDD), these are a hallmark of AMD that can exist even in the absence of conventional drusen. Eyes with RPD carry a substantial risk of progressing to geographic atrophy (GA) or type 3 neovascularization.
- Acquired Vitelliform Lesions (AVL): These yellowish subretinal deposits are often associated with RPD and represent a significant risk factor for atrophy following their resorption.
- Non-Exudative Macular Neovascularization (MNV): Advanced imaging can now detect neovascular complexes before they leak. Interestingly, while these eyes are at high risk for future exudation, stable type 1 MNV may actually provide metabolic support to the RPE, potentially slowing the expansion of atrophy.
- iRORA and cRORA: The Classification of Atrophy Meetings (CAM) group has introduced precise OCT-based definitions for atrophy. Incomplete RPE and outer retinal atrophy (iRORA) is a critical precursor, with most lesions progressing to complete RPE and outer retinal atrophy (cRORA) within 24 months.
- DRAMA and Non-Neovascular Fluid: The discovery of Deep Retinal Age-Related Microvascular Anomalies (DRAMA) and other forms of non-neovascular exudation challenges the long-held assumption that fluid in the retina always signifies a need for anti-VEGF therapy.
The Path Toward Precision Medicine
The future of AMD management lies in quantitative, imaging-integrated staging. Biomarkers like ellipsoid zone (EZ) loss and choroidal hypertransmission defects (hyperTDs) offer continuous, objective measurements of disease progression that are far more sensitive than binary events like “conversion to late AMD”.
By adopting a more nuanced classification system, clinicians can better identify high-risk eyes for closer monitoring, and researchers can ensure appropriate patient selection for emerging therapies. Moving beyond the drusen is not just a technical upgrade; it is a necessary shift to improve patient care in the era of precision ophthalmology.
According to the source, DRAMA stands for Deep Retinal Age-Related Microvascular Anomaly. It is a recently described type of microvascular anomaly that can be associated with non-neovascular exudation in eyes with age-related macular degeneration (AMD).
Key characteristics of DRAMA include:
- Clinical Presentation: They typically manifest as small-diameter perifoveal capillary dilations with hyperreflective walls located in the inner nuclear layer.
- Vascular Features: They can also appear as multiple vascular outpouchings extending posteriorly into the Henle fiber layer, possessing reflectivity similar to normal surrounding retinal capillaries.
- Pathophysiology: These anomalies may arise in a chronic ischemic state where functional insufficiency of the choriocapillaris elevates intraretinal VEGF levels, eventually promoting leakage from the deep vascular complex (DVC).
- Classification Status: DRAMA is not currently included in standard AMD classification systems, such as the Beckman classification. This means patients with these lesions may be classified into various stages (early, intermediate, or GA) depending on other present features, although their presence might indicate distinct underlying disease processes that could be considered for future classification updates.
Reference: Borrelli, E., Neri, G., Berni, A., et al. (2026). Review of emerging imaging findings to reveal a broader spectrum of lesions in AMD. Graefe’s Archive for Clinical and Experimental Ophthalmology. https://doi.org/10.1007/s00417-026-07335-9.
