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.

Objective: To evaluate multimodal imaging (MMI) biomarkers for predicting progression from intermediate to advanced age-related macular degeneration (AMD).

Methods: This prospective longitudinal cohort study included patients with intermediate AMD (iAMD) enrolled in the University of Colorado AMD registry between July 2014 and August 2023, with follow-up through February 2024. At enrolment, patients' medical histories and MMI were collected. Baseline and follow-up imaging were reviewed for progression to geographic atrophy (GA) and neovascular AMD (nAMD). Univariate and multivariable Cox proportional hazard modelling with competing risks to determine HRs for progression.

Results: A total of 367 patients (733 eyes) with iAMD were included in the study, with a median follow-up of 27.8 months. During this period, 100 eyes progressed to GA, 58 to nAMD. Adjusted for age, BMI and hypertension, progression to nAMD was significantly associated with soft drusen (HR 5.31, 95% CI 1.95 to 14.4, p=0.001), pigmentary changes (HR 2.74, 95% CI 1.52 to 4.92, p=0.0008) on colour fundus photography (CFP) and subretinal hyper-reflective material (SHRM) (HR 3.36, 95% CI 1.88 to 6.02, p<0.0001) and intraretinal hyper-reflective foci (IHRF) (HR 3.12, 95% CI 1.74 to 5.57, p=0.0001) on optical coherence tomography (OCT). Adjusted for age, progression to GA was predicted by soft drusen (HR 1.90, 95% CI 1.11 to 3.27, p=0.020), drusenoid pigment epithelial detachment (PED) (HR 5.51, 95% CI 2.49 to 12.2, p<0.0001), avascular non-drusenoid PED (HR 6.59, 95% CI 1.54 to 28.1, p=0.011), pigmentary changes (HR 4.44, 95% CI 2.84 to 6.96, p<0.0001) on CFP and nnSRF (HR 6.41, 95% CI 1.39 to 29.6, p=0.017), SHRM (HR 2.55, 95% CI 1.45 to 4.49, p=0.001), drusenoid PED (HR 2.25, 95% CI 1.43 to 3.55, p=0.0005), avascular non-drusenoid PED (HR 4.67, 95% CI 2.45 to 8.92, p<0.0001), IHRF (HR 6.27, 95% CI 3.89 to 10.1, p<0.0001) and incomplete retinal pigment epithelium and outer retinal atrophy (HR 9.42, 95% CI 5.82 to 15.2, p<0.0001) on OCT (table 3).

Conclusions: Key imaging biomarkers associated with the progression were identified, which may offer prognostic information for providers. However, the study is limited by its predominantly Caucasian population and single-centre design, which may affect the generalisability of certain biomarkers.