Clinical assessment and relationship of retinal fluorophores and microvascular modifications in early diabetic retinal disease in type 1 diabetes

Purpose: To quantify macular microvascular modifications and retinal fluorophores in early diabetic retinal disease (DRD) in type 1 diabetes mellitus (DM1), and to explore their interrelationship. Methods: One-hundred twenty-one subjects with DM1 and no diabetic retinopathy (noDR) or mild/moderate non-proliferative DR (NPDR) underwent optical coherence tomography (OCT), OCT-angiography (OCT-A), and spectrally resolved fundus autofluorescence (Sr-FAF). OCT-A was analyzed for perfusion/vessel density (PD/VD), fractal dimension (FD), vessel length density (VLD), geometric perfusion deficits (GPD), and foveal avascular zone metrics in the superficial and deep capillary plexuses (SCP/DCP). Sr-FAF green and red emission fluorescence component (GEFC/REFC) intensities in 9 ETDRS macular sectors were quantified. Mann-Whitney U test was used for group comparisons and Pearson’s coefficients for correlations between OCT-A and Sr-FAF. Results: One-hundred four eyes (50 noDR, 54 NPDR) were included. NPDR eyes showed lower PD, VD, FD, and VLD and higher GPD (p<0.001) in DCP vs noDR. GEFC intensity was higher in NPDR vs noDR in the nasal (p<0.01) and inner inferior (p=0.009) sectors and in the whole macular region(p=0.04); REFC intensity was higher in NPDR vs noDR at the fovea and in the inner nasal sector (p=0.01). In NPDR, DCP perfusion metrics correlated positively with GEFC and REFC values; in noDR, weak negative correlations were documented. Conclusions: Quantification of minor retinal fluorophores with Sr-FAF and microvascular assessment may provide novel insights into early DRD in DM1. Opposing correlation trends across disease stages suggest dynamic vascular-metabolic interactions. Sr-FAF may serve as a biomarker of retinal metabolic status, warranting further validation.