The Study Of The Association Between Retinal Microangiopathy And Ischemic Stroke Subtypes

Part 1 Association of retinal microvascular abnormalities and extracranial/intracranial large artery diseaseBackground and purpose: Previous studies focused on the association of retinal microvascular abnormalities(RMA)with risk of stroke due to the cerebral small vascular disease(CSVD),while less attentions were paid on the association with the extracranial / intracranial large artery disease.In this cross-sectional study,we aimed to investigate the association between RMA and the extravascular / intracranial large artery disease in patients with ischemic stroke by quantitative analysis of retinal vascular changes.Methods: Patients with AIS or TIA were continuous enrolled in this cohort from March 2017 to September 2018 at 2 comprehensive stroke centers in China.All patients underwent DSA or CTA or MRA examination and bilateral eye fundus photography.According to the highest stenosis rate of extracranial large artery disease(ICA,C1-C5),patients were divided into severe stenosis(?70%)and no severe stenosis(<70%).Similarly,intracranial large artery disease(ICA,C6-C7/MCA/ACA)were divided into severe stenosis(?70%)and no severe stenosis(<70%).Quantitative analysis of RMA with ipsilateral vessel stenosis were executed by a semi-automated measurement software VAMPIRE masked to clinical data,a revised Parr-Hubbard formula was used to compute Central Retinal Artery Equivalent(CRAE)andCentral Retinal Vein Equivalent(CRVE).Univariate analysis was performed to explore the differences of RMA between severe and non-severe stenosis.Logistic regression was performed to determine the relationship of RMA and severe stenosis with age-and gender-adjusted as well as multivariable-adjusted models.Results:There were 385 patients with AIS or TIA recruited in this study andaccomplished examination of the fundus photography and extracranial/intracranial large artery.A total of 328 patients were enrolled in this section after excluding the poor retinal imaging of the fundus.Patients with extracranial ICA severe stenosis had a wider CRVE(208.57 vs 200.83 ?m,P=0.012),lower AVR(0.59 vs 0.62,P=0.015)than those withoutextracranial ICA severe stenosis.There was no statistical difference in CRAE between patients with and without extracranial ICA severe stenosis(121.99 vs 123.37?m,P=0.819).In multivariate analysis,extracranial ICA severe stenosis was associated with retinal venular dilatation(OR=1.78;95% CI,1.17–2.70;P=0.006)and decreasing AVR(OR=0.68;95% CI,0.48–0.96;P=0.030).As for severe stenosis of intracranial large artery,there was no statistical difference in CRAE(125.78vs122.14?m,P=0.105),CRVE(203.15 vs 202.61?m,P=0.759)and AVR(0.62vs0.61,P=0.099).After multivariate adjustment,no association was identified with CRAE(OR=1.39;95% CI,0.97–1.99;P=0.075),CRVE(OR=1.13;95% CI,0.80–1.59;P=0.503)and AVR(OR=1.17;95% CI,0.87–1.57;P=0.304).Conclusions: Retinal venular widening,but not retinal artery narrower,was significantly associated with ipsilateral extracranial ICA severe stenosisin patients with acute ischemic stroke or TIA.All of them were not associated with ipsilateral intracranial large artery stenosis.Our findings suggest that carotid stenosis or occlusion,as the upstream blood vessel of ocular artery,might concomitant with retinal microvascular abnormalities in patients with AIS or TIA.Part 2 Association of retinal microvascular abnormalities and cerebral small vascular diseaseBackground and purpose: The association of the RMA with cerebral small vessel disease(CSVD)subtypes,such as lacunar stroke,white matter lesion and cerebral microbleed,were widely studied,while there was no established association of RMA with enlarged perivascular space(EPVS)or recent subcortical small infarction(RSSI).In this cross-sectional study,we aimed to investigate the association between retinal microvascular abnormalities and EPVS or RSSI in patients with acute ischemic stroke or TIA by quantitative analysis of retinal vascular changes.Methods: Patients with AIS or TIA were continuously enrolled in this prospective cohort from March 2017 to September 2018 at 2 comprehensive stroke centers in China.All patients underwent head MRI examination and bilateral eye fundus photography.Patients were divided into severe and non-severe EPVS based onEPVS grades.Similarly,patients were grouped as with RSSI and without RSSI.Quantitative analysis of retinal vessel with ipsilateral EPVS or RSSI was executed by a semi-automated measurement software VAMPIRE masked to clinical data,a revised Parr-Hubbard formula was used to compute Central Retinal Artery Equivalent(CRAE)and Central Retinal Vein Equivalent(CRVE).Univariate analysis was performed to explore the differences of RMA between severe and non-severe EPVS.Logistic regression was performed to determine the association of RMA and EPVS with age-and gender-adjusted as well as multivariable-adjusted models.Similar statistics analysis was performed in patients between RSSI and without RSSI.Results:A total of 286 patients with AIS or TIA were enrolled in this study.Patients with severe basal ganglia EPVS(EPVS-BG)had a narrower CRAE(120.26 vs 125.65?m,P=0.020),lower AVR(0.60 vs 0.63,P=0.006)than those without severe EPVS-BG.There was no statistical difference in CRVE between patients with and without severe EPVS-BG(202.49 vs 202.22?m,P=0.845).In multivariate analysis,severe EPVS-BG was associated with narrower retinal artery(OR=0.67;95% CI,0.50–0.92;P=0.015)and decreasing AVR(OR=0.69;95% CI,0.52–0.91;P=0.008).However,there was no association between CRVE and severe EPVS-BG(OR=1.37;95% CI,0.99–1.89;P=0.052).Similarly,enlarged perivascular spaces in the centrum semiovale(EPVS-CSO)had comparably results with EPVS-BG.As for RSSI,patients with RSSI had a narrower CRAE(119.15 vs 125.31 ?m,P=0.037)and decreasing venous bifurcation angle(74.36°vs 77.45°,P=0.025)than those without RSSI in univariate analysis.In multivariate analysis,RSSI was associated with venous bifurcation angle(OR=0.72;95% CI,0.53–0.96;P=0.027).However,no association were identified with CRAE(OR=0.73;95% CI,0.53–1.01;P=0.057),CRVE(OR=1.05;95% CI,0.76–1.44;P=0.777)and AVR(OR=0.82;95% CI,0.62–1.07;P=0.148)after multivariate adjustment.Conclusions: Retinal artery caliber was significantly associated with ipsilateral severe EPVS-BG and EPVS-CSO in patients with AIS or TIA,but no association with ipsilateral RSSI.Therefore,this study provided clues for further exploration of pathogenesis of EPVS and RSSI.