Imaging Biomarkers To Predict Progression of Intermediate AMD with Avascular Pigment Epithelial Detachment in the University of Colorado AMD Registry

Purpose: To investigate whether specific imaging biomarkers predict progression to neovascular AMD (nAMD) or geographic atrophy (GA) in eyes with high-risk intermediate age-related macular degeneration (iAMD) and avascular pigment epithelial detachment (PED). Methods: Prospective longitudinal cohort study of eyes with iAMD and avascular PED from the University of Colorado AMD registry (August 2014 - August 2023) with ≥1 month of follow-up through February 2024. Multimodal imaging, including color fundus photos (CFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT), was graded by two reviewers for presence of specific imaging biomarkers. Time-to-progression survival analysis was conducted with hazard ratios calculated. Results: Over a median follow-up period of 35 months, 224 eyes (142 patients) were included. 31 (13.8%) eyes progressed to nAMD, and 63 (28.1%) to GA. Progression to nAMD was significantly predicted by pigmentary changes on CFP (HR=4.43 (95%CI: 1.77, 11.1), p=0.001) and intraretinal hyperreflective foci (iHRF) on OCT (HR=4.90 (95%CI: 2.02, 11.9), p=0.0005). Progression to GA was significantly predicted by pigmentary changes on CFP (HR=3.60 (95%CI: 1.94, 6.67), p<0.0001), iHRF (HR=4.13 (95%CI: 2.14, 7.94), p<0.0001), acquired vitelliform lesions (AVL; (HR=2.97 (95%CI: 1.55, 5.68), p=0.001)) and incomplete retinal pigment epithelium and outer retina atrophy (iRORA; (HR=4.18 (95%CI: 1.52, 11.4), p=0.006)). No other biomarkers demonstrated significance. Conclusion: In eyes with avascular PED, pigmentary changes and iHRF were significantly associated with progression to nAMD and GA, while AVL and iRORA were specifically to GA. We highlight in this study important imaging biomarkers that help identify high-risk eyes that may warrant closer monitoring to ensure timely therapeutic intervention.