Age-Related Reductions in Retinal Vessel Density Partly Reflect Vessel Calibre: A Two-Centre Fundus Imaging Study

Purpose: To examine relationships among age, retinal vessel calibre, and vessel density, and determine whether arterial and venous calibre statistically account for part of the association between age and corresponding vessel density. Materials and Methods: This retrospective cross-sectional study included 384 eligible right-eye colour fundus image records from two clinical centres. Retinal vascular measurements were obtained using AutoMorph. Composite scores were derived for arterial and venous calibre and vessel density using measurements from the full analysed field and standard retinal zones. A parallel partial-mediation model evaluated arterial and venous pathways simultaneously, adjusting for sex, centre, and age-by-centre interaction. Indirect effects were assessed using 2,000 centre-stratified bootstrap resamples. Results: Mean age was 40.54 ± 16.13 years; 159 records (41.4%) were male. Older age was associated with smaller arterial (β = −0.531) and venous calibre (β = −0.413; both P < 0.001). Larger calibre was associated with greater corresponding vessel density (arterial β = 0.267; venous β = 0.356; both P < 0.001). Age remained directly associated with lower arterial (β = −0.211) and venous density (β = −0.241; both P < 0.001). Indirect effects through arterial and venous calibre were −0.142 (95% CI, −0.183 to −0.100) and −0.147 (95% CI, −0.191 to −0.105), accounting statistically for 40.2% and 38.0% of the respective total associations. Conclusions: Retinal vessel calibre accounted statistically for approximately two-fifths of the association between older age and lower arterial and venous vessel density, while substantial direct age associations remained. These findings demonstrate that age-related reductions in area-based retinal vessel density cannot be interpreted as vascular rarefaction alone, because vessel width contributes directly to the segmented vascular area. The indirect effects therefore represent statistical decomposition rather than evidence of causal mediation. Joint assessment of vessel calibre, density, and vascular complexity may provide a more informative characterisation of retinal vascular ageing.