Longitudinal Systemic C-Reactive Protein and Risk of Progression to Advanced Age-Related Macular Degeneration

Purpose: To assess whether longitudinally measured systemic high-sensitivity C-reactive protein levels are associated with time to progression to any advanced age-related macular degeneration (AMD) or AMD phenotypes in a cohort of subjects with intermediate AMD (iAMD). Methods: Medical records were obtained from subjects in the University of Colorado AMD Registry (enrolled 2014–2023) with at least 1 month of follow-up. Cox proportional hazards models were used to calculate hazard ratios (HRs) from joint models estimating the association between longitudinally measured systemic high-sensitivity C-reactive protein and time to progression to advanced AMD. Results: A total of 428 subjects with iAMD were enrolled. During the 1828 person-years of follow-up, 18% of subjects showed progression to geographic atrophy (GA), and 14% had progression to neovascular AMD. Analyzed as a continuous variable, high-sensitivity C-reactive protein levels (mg/L) were not associated with time to progression to any advanced AMD (HR, 1.13, 95% credible interval [95% CrI], 0.57 to 2.23; P = .71), time to progression to GA (HR, 1.21, 95% CrI, 0.44 to 3.27; P = .71), or time to progression to neovascular AMD (HR, 1.03, 95% CrI, 0.43 to 2.50; P = .95). Examined as a dichotomous variable by decile, high-sensitivity C-reactive protein was not associated with progression to any advanced AMD for any dichotomization threshold assessed. Conclusions: The findings suggest that longitudinally measured systemic high-sensitivity C-reactive protein is not a useful biomarker for the timing of progression from iAMD to advanced AMD phenotypes.