Connections Reinforced Between Biomarkers and Age-Related Macular Degeneration

A recent prospective longitudinal cohort study indicated that various multimodal imaging (MMI) biomarkers may be reliable identifiers for patients with potential neovascular age-related macular degeneration (nAMD) or geographic atrophy (GA).

Various studies have indicated several different imaging biomarkers as reliable methods of predicting individuals at risk of developing nAMD, such as hyperreflective foci (HRF), pigment epithelial detachment (PED), subretinal drusenoid deposits (SDD), and so on.2

“Prior studies have identified several potential OCT biomarkers associated with progression to late AMD,” Ramya Gnanaraj, MD, department of ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, and colleagues wrote. “Our study aimed to validate the established biomarkers across a different patient population and geographic location.”1

The team interviewed and studied 367 patients, all of whom exhibited intermediate AMD and were enrolled in the University of Colorado AMD registry between 2014 and 2023. Requirements included an age between 55-99 and the presence of AMD in 1 or both eyes. Those with active retinal or uveitic diseases affecting the macula were excluded.1

Investigators followed up with participants through February of 2024. At baseline and follow-up, images were taken of participants’ eyes to review for geographic atrophy and nAMD progression. Imaging included color fundus photography (CFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT).1

Investigators found during the follow-up period that 100 eyes (13.6%) progressed to GA and 58 eyes (7.9%) progressed to nAMD. Median time to progression was 90 months. After adjusting for age, the team noted that progression to nAMD was associated most with soft drusen (hazard ratio [HR] 5.31, 95% CI: 1.95-14.4, P =.001) and pigmentary changes (HR 2.47, 95% CI: 1.52-4.92, P =.0008) on CFP, as well as subretinal hyper-reflective material (SHRM) (HR 3.36, 95% CI: 1.88-6.02, P<.0001) and intraretinal hyper-reflective foci (IHRF) (HR 3.12, 95% CI: 1.74-5.57, P =.0001) on OCT.1

Gnanaraj and colleagues indicated that progression to GA was most associated with soft drusen (HR 1.90, 95% CI: 1.11-3.27, P =.020), drusenoid PED (HR 5.51, 95% CI: 2.49-12.2, P<.0001), avascular non-drusenoid PED (HR 6.59, 95% CI: 1.54-28.1, P =.011), and pigmentary changes (HR 4.44, 95% CI: 2.84-6.96, P =.0001) on CFP and non-neovascular subretinal fluid (nnSRF) (HR 6.41, 95% CI: 1.39-29.6, P =.017), SHRM (HR 2.55, 95% CI: 1.45-4.49 P =.001), drusenoid PED (HR 2.25, 95% CI: 1.43-3.55, P =.0005), avascular non-drusenoid PED (HR 4.67, 95% CI: 2.45-8.92, P<.0001), IHRF (HR 6.27, 95% CI: 3.89-10.1, P<.0001) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) (HR 9.42, 95% CI: 5.82-15.2, P<.0001) on OCT.1

These findings, Gnanaraj and colleagues point out, solidifies the connection between a plethora of MMI biomarkers and the progression from AMD to advanced disease. Several common biomarkers (prevalence >5%) had a significant association with GA but not nAMD. Moreover, only 2 biomarkers, drusenoid PED and iRORA, were associated solely with GA, and every successful predictor of nAMD was also associated with GA. This, the team suggests, implies differences in the paths to each disease.1

Ultimately, Gnanaraj and colleagues indicated that these results will help ophthalmologists prioritize the most likely predictive biomarkers for nAMD and GA, thereby making diagnosis more efficient and accurate.1

“Identifying patients with these biomarkers can help predict outcomes and allow healthcare providers to monitor them more closely for timely treatment,” wrote Gnanaraj and colleagues. “In the future, these biomarkers can also contribute to selecting patients for early treatment trials.”1

References

1. Gnanaraj R, Lisker-Cervantes A, Patnaik J, et al. Multimodal imaging biomarkers for progression from intermediate to advanced age-related macular degeneration (AMD): a 10-year prospective longitudinal cohort study from the University of Colorado AMD registry. BMJ Open Ophthalmol. 2025;10(1):e002112. Published 2025 Apr 5. doi:10.1136/bmjophth-2024-002112

2. Manafi N, Mahmoudi A, Emamverdi M, et al. Topographic analysis of local OCT biomarkers which predict progression to atrophy in age-related macular degeneration. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2024;262(7):2083-2091. doi:10.1007/s00417-024-06389-x