Duration-Dependent Decoupling of the Macular Neurovascular Unit in Type 2 Diabetes Without Retinopathy: A Topographic Analysis Using Ultra-Widefield OCT Angiography.

To characterize duration-dependent topographic macular neurovascular unit (NVU) alterations in type 2 diabetes (T2DM) without diabetic retinopathy (DR) using 26×21 mm ultra-widefield swept-source OCT angiography (UWF-SS-OCTA) and evaluate its diagnostic utility for long-duration eyes.

This cross-sectional study included 295 eyes (69 controls; 226 T2DM without DR stratified by duration: <5, 5-10, ≥10 years). The superficial vascular density (SVD), deep vascular density (DVD), superficial macular vascular density (SMVD), and nerve-fibre-layer microvascular density (NFMVD) were quantified in the fovea (1 mm), inner (1-12 mm) and outer (12-21 mm) rings and their quadrants. Ganglion cell-inner plexiform layer (GCIPL) thickness was derived from the 26 × 21 mm OCTA scan. ANCOVA adjusted for age, sex, BMI, hypertension, IOP with false discovery rate correction, multivariable regression, and ROC/decision curve analyses were used.

Longer duration was associated with progressive GCIPL thinning and deep-predominant DVD reduction across nearly all macular zones (q<0.05); the DVD deficit was most pronounced in the outer ring. SVD showed nasal-temporal asymmetry; selective nasal inner loss in ≥10-year group. GCIPL-DVD coupling, present in controls, attenuated in ≥10-year group, indicating NVU decoupling. Duration independently predicted GCIPL (β=-0.21) and DVD (β=-0.27) after adjustment (P<0.01). DVD alone discriminated ≥10-year eyes from controls (AUC 0.723, 95% CI 0.63-0.81); addition of GCIPL did not improve AUC (0.724, P>0.05). Decision curve analysis confirmed net clinical benefit.

Preclinical NVU decoupling-predominantly in the deep capillary plexus and nasally asymmetric-already occurs in T2DM without fundoscopic DR and progresses with disease duration. Deep-layer UWF-SS-OCTA metrics may strengthen risk stratification before clinical retinopathy.
Diabetes
Diabetes type 2
Care/Management

Authors

Chen Chen, Zhang Zhang, Shen Shen, Huang Huang, Ye Ye, Huang Huang, Yan Yan, Song Song
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