OCT Biomarkers Distinguish Progression to Neovascular vs. Atrophic AMD in Intermediate Disease
Key Insights
A multicenter study identified four baseline OCT biomarkers—double-layer sign, greatest drusen height, hyperreflective foci, and iRORA—that help anticipate whether intermediate AMD will progress to neovascular or atrophic disease.
Among 154 eyes followed for one year, 57% converted to neovascular AMD (search) and 43% to geographic atrophy (search), with double-layer sign emerging as the strongest predictor of neovascularization.
Eyes progressing to geographic atrophy (search) showed larger drusen (mean height 144 μm vs. 100 μm) and higher iRORA prevalence (65% vs. 13%) compared with neovascular converters.
A new multicenter study published in the journal Eye suggests that routine structural optical coherence tomography (OCT) imaging at the intermediate age-related macular degeneration (search) (iAMD) stage may help clinicians anticipate whether patients are more likely to progress to neovascular AMD (search) (nAMD) or geographic atrophy (search) (GA)—two late-stage forms of the disease with very different treatment implications. Researchers found that four baseline OCT biomarkers were especially useful for distinguishing future neovascular from atrophic conversion: double-layer sign, greatest drusen height, hyperreflective foci, and incomplete retinal pigment epithelial and outer retinal atrophy (iRORA).
Given the distinct management pathways and treatment options for neovascular AMD (search) versus geographic atrophy (search), the OCT predictors identified in this study could help clinicians anticipate the most likely disease trajectory, guide referral urgency, and tailor monitoring.
Study Design and Patient Population
The retrospective longitudinal study enrolled 154 eyes from 154 patients with iAMD seen at three retinal referral centers in Italy and France. All patients were older than 55 years and had no evidence of GA or nAMD at baseline, but they were considered high risk and converted to late AMD within one year. Eyes with prior retinal treatment, other retinal disease, or inadequate imaging were excluded. If both eyes were eligible, only the eye with the better image quality was included.
At baseline, the cohort was older (mean age: 80 years), and most participants were women (70%). Several OCT biomarkers were identified among the study population, including drusen and reticular pseudodrusen (67% of eyes), basal laminar deposits (74%), hyperreflective foci at the lesion site (56%), iRORA (35%), and double-layer sign (34%).
Divergent Progression Pathways
After one year of follow-up, 88 eyes (57%) progressed to nAMD and 66 eyes (43%) to GA. Visual acuity worsened in both groups: in eyes that developed nAMD, best-corrected visual acuity (BCVA) declined from 0.13 ± 0.10 logMAR to 0.30 ± 0.24 logMAR; in eyes that became GA, BCVA worsened from 0.19 ± 0.18 logMAR to 0.30 ± 0.29 logMAR. Among nAMD converters, subtype distribution was 45% type 1, 7% type 2, and 48% type 3 macular neovascularization. In the GA group, the mean atrophy area at one year was 0.74 ± 1.10 mm².
Biomarkers That Differentiate Disease Trajectory
The researchers observed that eyes that later developed nAMD had a higher prevalence of double-layer sign (77% vs. 52%) and basal laminar deposits (81% vs. 65%). Conversely, eyes that later developed GA had larger drusen and more atrophy-related features. Mean drusen height was 144 ± 86 μm in the GA group versus 100 ± 43 μm in the nAMD group, and mean drusen diameter was 810 ± 751 μm versus 473 ± 362 μm. Hyperreflective foci (HRF) was also more frequent in the GA group, both at the lesion site (67% vs. 48%) and elsewhere (77% vs. 57%). Finally, iRORA was strongly associated with GA conversion (65% vs. 13%).
While the researchers were unable to identify a threshold value, they wrote in their paper, "The identification of only four biomarkers in the clinical setting (i.e., identification of great drusen, presence of double-layer sign, hyperreflective foci and iRORA) could help us in discerning possible progression to GA vs nAMD."
Clinical Implications for Monitoring and Treatment
As GA treatments continue to advance, the ability to anticipate the likely direction of progression through these structural biomarkers could improve referral timing and monitoring frequency, the researchers explained. They elaborated, "In the atrophic form, we could promptly identify patients who might benefit from currently available strategies to slow the progression of the disease, preserving as much retinal tissue as possible. For the neovascular form, it is important to promptly identify patients who progress to the exudative form so they can be treated correctly and manage retinal fluids as soon as possible."
Future studies will help validate these findings in broader patient populations, refine OCT-based risk models, and determine how well they perform in everyday clinical practice, the study authors concluded.