Retinal and microvascular alterations in Alport syndrome: a multimodal imaging study

Alport syndrome (AS) is a hereditary disorder caused by mutations in type IV collagen genes and is frequently associated with ocular manifestations. Although anterior segment findings are well described, retinal structural and microvascular alterations in AS remain insufficiently characterized. This study aimed to comprehensively characterize retinal structural and microvascular alterations in patients with AS using spectral-domain optical coherence tomography (SD-OCT) and swept-source OCT angiography (SS-OCTA). This retrospective cross-sectional study included 68 eyes of 34 patients with genetically or clinically confirmed AS and 68 eyes of 68 age- and sex-matched healthy controls. Retinal layer thickness was measured at 500, 1000, 1500, and 3000 μm from the foveal center in the nasal and temporal quadrants using SD-OCT. SS-OCTA was used to quantify the foveal avascular zone (FAZ) area, acircularity index (AI), and vessel density (VD) in the superficial and deep capillary plexuses and flow/non-flow areas. All segmentations were manually reviewed and corrected accordingly. Intra-subject correlations were accounted for using generalized estimating equations with false discovery rate corrections for multiple comparisons. Eyes with AS exhibited significant temporal macular thinning at all eccentricities (p < 0.001), predominantly involving the inner retinal layers but also affecting the outer plexiform and outer nuclear layers. The FAZ area was significantly smaller in the AS group than in the control group (0.19 ± 0.10 vs. 0.28 ± 0.10 mm²; p < 0.001), whereas the AI was higher (1.13 ± 0.07 vs. 1.10 ± 0.04; p = 0.025). VD was significantly reduced in both capillary plexuses, particularly in temporal and inferior quadrants (p < 0.001). Patients with foveal hypoplasia were excluded. AS is associated with temporal retinal thinning that extends from the inner to outer retinal layers, together with significant microvascular alterations predominantly in the temporal macula. These multimodal OCT and OCTA findings provide novel insights into the pathophysiology of the disease and highlight their potential as non-invasive biomarkers for the early detection and longitudinal monitoring of ocular involvement in AS. This retrospective cross-sectional study evaluated retinal layer thickness and capillary plexus density in patients with Alport syndrome using OCT and OCT-A, and revealed significant temporal macular thinning and microvascular alterations in these patients compared to healthy controls. What is already known about this topic Temporal macular thinning is a hallmark OCT finding in Alport syndrome, predominantly affecting the inner retinal layers due to type IV collagen abnormalities. What this study adds This study demonstrates that retinal thinning in Alport syndrome also significantly involves the outer retinal layers, including the outer plexiform and outer nuclear layers, challenging the previously held notion of isolated inner retinal involvement in the disease.