Assessment of vascular tortuosity in 22q11.2 deletion syndrome using optical coherence tomography angiography

Purpose To quantify retinal vascular tortuosity and assess microvascular alterations in 22q11.2 deletion syndrome (22q11.2DS) using optical coherence tomography angiography (OCTA). Methods This observational cross-sectional study analyzed 108 eyes from 27 patients with 22q11.2DS and 27 age- and sex-matched controls. OCTA parameters included vascular density in the superficial and deep capillary plexuses (SCP, DCP), radial peripapillary capillaries (RPC), and foveal avascular zone (FAZ). A skeletonized vascular model was generated from 6mm × 6mm OCTA images of the superficial plexus after Otsu binarization using Fiji (ImageJ). The vascular tortuosity index (VTI) was computed as the ratio of total vessel length to Euclidean distance via the AnalyzeSkeleton function. A generalized estimating equation (GEE) model accounted for intra-eye correlation, and a probit regression model identified OCTA predictors of 22q11.2DS. Results OCTA revealed significantly lower vascular density in both SCP and DCP in 22q11.2DS patients. DCP density was reduced across all regions, including whole-image (p<0.001), superior (p<0.001), inferior (p<0.001), and foveal regions (p=0.020). No significant differences were found in FAZ area or RPC density. VTI was significantly higher in 22q11.2DS (p=0.001). Probit regression identified DCP whole-image density (p=0.009) and VTI (p=0.028) as predictors of 22q11.2DS, with a pseudo-R² of 0.23. Conclusions VTI was identified as a predictor of 22q11.2DS, providing an objective measure of retinal vascular tortuosity. OCTA revealed previously unrecognized microvascular alterations, supporting its use as a non-invasive tool for vascular assessment in this population.