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Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure. 

Précis:Capillary and neuronal tissue loss occur both globally and with regional specificity in pre-perimetric glaucoma patients at the level of the optic nerve and macula, with perifovea regions affected earlier than parafovea areas. Purpose:To investigate optic nerve head (ONH) and macular vessel densities (VD) and structural parameters assessed by optical coherence tomography angiography in pre-perimetric open angle glaucoma (ppOAG) patients and healthy controls. Materials and Methods:In all, 113 healthy and 79 ppOAG patients underwent global and regional (hemispheric/quadrants) assessments of retinal, ONH, and macular vascularity and structure, including ONH parameters, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness. Comparisons between outcomes in ppOAG and controls were adjusted for age, sex, race, BMI, diabetes, and hypertension, withP<0.05 considered statistically significant. Results:In ppOAG compared with healthy controls: RNFL thicknesses were statistically significantly lower for all hemispheres, quadrants, and sectors (P<0.001–0.041); whole image peripapillary all and small blood vessels VD were statistically significantly lower for all the quadrants (P<0.001–0.002), except for the peripapillary small vessels in the temporal quadrant (ppOAG: 49.66 (8.40), healthy: 53.45 (4.04);P=0.843); GCC and inner and full macular thicknesses in the parafoveal and perifoveal regions were significantly lower in all the quadrants (P=0.000–P=0.033); several macular VD were significantly lower (P=0.006–0.034), with the exceptions of macular center, parafoveal superior and inferior quadrant, and perifoveal superior quadrant (P>0.05). Conclusions:In ppOAG patients, VD biomarkers in both the macula and ONH, alongside RNFL, GCC, and macular thickness, were significantly reduced before detectable visual field loss with regional specificity. The most significant VD reduction detected was in the peripheric (perifovea) regions. Macular and ONH decrease in VD may serve as early biomarkers of glaucomatous disease.