The impact of acute COVID-19 on the retinal microvasculature assessed with multimodal imaging

Abstract

Purpose To quantify retinal microvascular findings in the acute phase of COVID-19 using multimodal imaging and compare them with healthy, age-matched controls. Methods Hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities ( n = 75) and healthy controls ( n = 101) aged 18–65 were enrolled in this prospective cross-sectional study. The retinal microcirculation and microvasculature impairments were assessed using fundus photography, swept-source optical coherence tomography, and swept-source optical coherence tomography angiography in the COVID-19 unit and compared with healthy, age-matched controls. Results Retinal findings were predominately observed in patients with severe disease ( P = 0.006). Patients with severe disease were shown to have increased both mean vein diameter (Coef. = 19.28, 95% CI: 7.34–31.23, P = 0.002) and mean artery diameter (Coef. = 11.07, 95% CI: 0.84–21.67, P = 0.044). Neither blood vessel diameters were correlated with any confounding variables (age, sex, treatment with oxygen, LDH, or ferritin). Patients with severe COVID-19 were shown to have significantly increased retinal nerve fiber layer thickness in the superior and inferior quadrants both in the inner (S: P = 0.046; I: P = 0.016) and outer (S: P = 0.026; I: P = 0.014) ring and significantly increased GCL thickness in the outer temporal quadrant ( P = 0.038). There were no statistically significant differences in vessel density or the foveal avascular zone area between the groups. Conclusion The severity of COVID-19 was significantly correlated with the presence of retinal microangiopathy, which could become a biomarker of angiopathy in patients with COVID-19.

The Comparison of Retinal Microvascular Findings in Acute COVID-19 and 1-Year after Hospital Discharge Assessed with Multimodal Imaging—A Prospective Longitudinal Cohort Study

“…We found a significantly decreased MVD and a tendency toward a decrease in MAD at 1-year follow-up. These results are especially interesting, given that the significantly increased mean vessel diameters of both veins and arteries were present in hospitalized patients with severe COVID-19 in our previous study [ 16 ]. Similar results were reported, where a significantly decreased MVD and MAD were present after a 6-month follow-up; however, their baseline measurements were not performed in the acute phase of COVID-19 [ 37 , 38 ].…”

“…COVID-19 retinopathy, encompassing several retinal findings, such as flame-shaped hemorrhages, cotton wool spots, dilated veins, and tortuous vessels, have been previously described. Furthermore, increased RNFL thickness and increased GCL thickness in several quadrants of the inner and outer EDTRS ring were described in the acute phase of severe COVID-19 [ 16 ]. The studies regarding the vessel density (VD) of the superficial and deep capillary plexuses have been inconclusive.…”

“…Individuals with a D/D genotype, which leads to an increased serum ACE concentration, were shown to have higher rates of pulmonary embolism and COVID-19-related mortality [ 18 , 25 , 26 ]. Conflicting results regarding the role of ACE2-related polymorphisms have been published [ 16 , 19 , 20 , 21 ]. It was hypothesized that the presence of A-allele, linked to increased gene expression of ACE2, resulting in higher ACE2 serum levels, and therefore and an increased number of viral binding sites, could increase COVID-19 severity [ 19 , 21 ].…”

“…Therefore, the presence of A-allele was found to have a protective role, possibly explained by counterbalancing of the effects of increased Ang II resulting from the RAAS dysregulation [ 33 ]. Nonetheless, several studies found no association with disease susceptibility or severity [ 16 , 20 , 21 ]. An increased risk of severe COVID-19 was also associated with an AGTR2 polymorphism (rs1914711) [ 27 ].…”

“…An increased risk of severe COVID-19 was also associated with an AGTR2 polymorphism (rs1914711) [ 27 ]. It is noteworthy that ACE, ACE2, and AGTR2 polymorphisms have also been associated with hypertension, diabetes, coronary artery disease, and stroke [ 16 , 17 , 18 , 19 , 20 , 21 ], which complicates the risk estimation, as those comborbities alone are associated with an increased risk of COVID-19. Nevertheless, our previous study, focusing on patients without known comorbidities, showed an increased risk of COVID-19 retinopathy in males with the AGTR2-AA genotype of the rs1403543 polymorphism [ 34 ].…”