Atrial fibrillation and retinal imaging-based oculomics: A cross-sectional and longitudinal analysis of two large cohorts

We investigate the association between multimodal retinal imaging parameters with prevalent and incident atrial fibrillation (AF). For this cross-sectional and longitudinal analysis we utilized data from two independent cohorts: AlzEye (retrospective, age ≥ 40 years, 2008–2018) and UK Biobank (UKB; prospective, age 40–69 years, recruited 2006–2010). Retinal sublayer thicknesses and retinovascular indices were extracted from macular optical coherence tomography and color retinal photography, respectively. AF was ascertained via self-report and hospital admissions, association between retinal metrics with prevalent and incident AF were estimated using mixed-effects linear and frailty models. In AlzEye (n = 50,651), prevalent AF (n = 5,375; 11%) was associated with significantly smaller retinal venular calibre (-0.05 µm, 95% CI: -0.08, -0.03) and thinner macular retinal nerve fibre layer (-0.69 µm, 95% CI: -0.91, -0.46), ganglion cell-inner plexiform layer (mGCIPL; -1.96 µm, 95% CI: -2.34, -1.58), inner nuclear layer (-0.57 µm, 95% CI: -0.75, -0.38), and photoreceptor layer (-0.93 µm, 95% CI: -1.38, -0.48). Venular fractal dimension was lower (-0.08, 95% CI: -0.11, -0.06), while arteriolar fractal dimension was higher (0.05, 95% CI: 0.02, 0.08) in individuals with AF. Evidence of thinner mGCIPL was replicated in UKB (-1.19 µm, 95% CI: -1.73, -0.65). In UKB (n = 39,013 baseline without AF), 838 developed AF over a mean of 4.0 years. Adjusting for sociodemographic, clinical and lifestyle factors, each SD decrease in mGCIPL thickness was associated with a significant 27% increased hazard of AF (95% CI: 5%, 54%). Differences in the inner retinal sublayers, corresponding to retinal ganglion cells, are associated with prevalent and incident AF across two large independent cohorts, supporting the potential role of widely-accessible retinal imaging for early detection and better management of AF.