Retinal and Choroidal Metrics Are Dynamic Markers of the Maternal Vascular Response to Pregnancy

BACKGROUND: There is an unmet need for biomarkers that can dynamically track maternal vascular health and guide interventions in disordered pregnancies. The retina and choroid provide a window into the systemic vasculature. We aimed to characterize longitudinal trajectories of retinal and choroidal features during healthy pregnancy and explore differences associated with preeclampsia. METHODS: Overall, 251 pregnant women underwent multimodal retinal imaging with color fundus photography, scanning laser ophthalmoscopy, and optical coherence tomography at multiple antenatal (12±3 or 20±3 weeks’ gestation and 36±3 weeks’ gestation, n=183) or a single third-trimester (36±3 weeks’ gestation, n=68) time point. Retinal and choroidal vascular features were extracted using an automated pipeline. We examined gestational trajectories of these features and their associations with blood pressure change and serum angiogenic factors. Trajectories were compared for women with preeclampsia and those without placental dysfunction. RESULTS: Significant reductions in measurements of retinal vessel caliber and density and of choroidal thickness, and increases in retinal thickness measurements, were seen over healthy pregnancy. These changes were not correlated with maternal blood pressure change. Third-trimester retinal arteriolar caliber and density were weakly correlated with placental growth factor ( r =0.32, P <0.001 and r =0.31, P <0.001) and soluble fms-like tyrosine kinase 1 ( r =−0.21, P =0.006 and r =−0.33, P <0.001) levels. Preeclampsia was associated with significantly greater reductions in retinal arteriolar caliber ( P =0.022 for right eye, P =0.019 for left) and density ( P <0.001 for each eye) across gestation. CONCLUSIONS: Retinal and choroidal features change throughout pregnancy, and these trajectories are altered in preeclampsia. REGISTRATION: URL: xxx; Unique identifier: ISRCTN40843826.