Structural and causal links between retinal vascular geometry and neural layer thickness

Abstract

Purpose: To investigate structural relationships between retinal vasculometry from color fundus photography (CFP) and neural layers obtained from Optical Coherence Tomography (OCT) scans. Methods: This cross-sectional study used the Retina-based Microvascular Health Assessment System (RMHAS) to extract retinal vascular measurements in the 6*6 mm area centered on the macular region and analyzed their associations with OCT parameters. We investigated both pairwise correlations between individual retinal layers and vascular parameters and associations between sets of variables. Mendelian randomization was employed to investigate potential causality. Results: Data from 67,918 eyes of 43,029 participants were included. Among neural layers, Ganglion Cell-Inner Plexiform Layer (GC-IPL) showed the most notable correlations with vascular Density and Complexity (r = 0.199 for arterial Vessel Area Density and r = 0.175 for Number of Segments). Inner Nuclear Layer (INL) thickness correlated with Width (r = 0.122) and arterial Vessel Area Density (r = 0.127). Mendelian randomization indicated a bidirectional causal relationship. Genetically predicted higher Vessel Density was associated with increased thickness across various retinal layers, with standardized effect size of 1.50 on Inner Segment/Outer Segment + Photoreceptor Segment thickness. Genetically predicted increases in retinal layer thicknesses, particularly the Outer Plexiform Layer, were linked to higher Vessel Density (standardized effect size 0.45) and Fractal Dimension (standardized effect size 0.48). Conclusions: GC-IPL and INL were positively associated with vascular Density and Caliber. Multidimensional relationships indicate a complementary nature between retinal vascular and neural parameters, highlighting their value as a composite biomarker. Mendelian Randomization uncovered a bidirectional causal relationship, providing insights into novel therapeutic approaches targeting vascular and neuronal components.