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

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.

This study aimed to quantify possible long-term impairment of the retinal microcirculation and microvasculature by reassessing a cohort of patients with acute COVID-19 without other known comorbidities one year after their discharge from the hospital. Thirty patients in the acute phase of COVID-19 without known systemic comorbidities were enrolled in this prospective longitudinal cohort study. Fundus photography, SS-OCT, and SS-OCTA using swept-source OCT (SS-OCT, Topcon DRI OCT Triton; Topcon Corp., Tokyo, Japan) were performed in the COVID-19 unit and 1-year after hospital discharge. The cohort's median age was 60 years (range 28-65) and 18 (60%) were male. Mean vein diameter (MVD) significantly decreased over time, from 134.8 µm in the acute phase to 112.4 µm at a 1-year follow-up (p < 0.001). A significantly reduced retinal nerve fiber layer (RNFL) thickness was observed at follow-up in the inferior quadrant of the inner ring (mean diff. 0.80 95% CI 0.01-1.60, p = 0.047) and inferior (mean diff. 1.56 95% CI 0.50-2.61, p < 0.001), nasal (mean diff. 2.21 95% CI 1.16-3.27, p < 0.001), and superior (mean diff. 1.69 95% CI 0.63-2.74, p < 0.001) quadrants of the outer ring. There were no statistically significant differences between the groups regarding vessel density of the superior and deep capillary plexuses. The transient dilatation of the retinal vessels in the acute phase of COVID-19, as well as RNFL thickness changes, could become a biomarker of angiopathy in patients with severe COVID-19.

The Role of ACE, ACE2, and AGTR2 Polymorphisms in COVID-19 Severity and the Presence of COVID-19-Related Retinopathy.

The proposed SARS-CoV-2-induced dysregulation of the renin-angiotensin-aldosterone (RAAS) system results in endothelial dysfunction and microvascular thrombosis. The retinal plexuses contain terminal vessels without anastomotic connections, making the retina especially susceptible to ischemia. This study aimed to determine the role of selected polymorphisms of genes in the RAAS pathway in COVID-19 severity and their association with the presence of COVID-19 retinopathy. 69 hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities and 96 healthy controls were enrolled in this prospective cross-sectional study. The retina was assessed with fundus photography using a Topcon DRI OCT Triton (Topcon Corp., Tokyo, Japan) in the COVID-19 unit. Genotyping of selected polymorphisms in the genes for ACE (rs4646994), ACE2 (rs2285666), and AGTR2 (rs1403543) was performed. The COVID-19 group was divided into mild (n = 12) and severe (n = 57), and then further divided according to the presence of COVID-19 retinopathy (Yes, n = 50; No, n = 19). The presence of the AGTR2 rs1403543-AA genotype was associated with a 3.8-fold increased risk of COVID-19 retinopathy (p = 0.05). The genotype frequencies of selected gene polymorphisms were not significantly associated with either the presence of COVID-19 or its severity. This is the first study demonstrating a borderline association of the AGTR2 rs1403543-AA genotype with COVID-19 retinopathy in males; hence, the AGTR2 rs 1403543 A allele might represent a genetic risk factor for COVID-19 retinopathy in males.

The Role of ACE, ACE2, and AGTR2 Polymorphisms in COVID-19 Severity and the Presence of COVID-19-Related Retinopathy

The proposed SARS-CoV-2-induced dysregulation of the renin-angiotensin-aldosterone (RAAS) system results in endothelial dysfunction and microvascular thrombosis. The retinal plexuses contain terminal vessels without anastomotic connections, making the retina especially susceptible to ischemia. This study aimed to determine the role of selected polymorphisms of genes in the RAAS pathway in COVID-19 severity and their association with the presence of COVID-19 retinopathy. 69 hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities and 96 healthy controls were enrolled in this prospective cross-sectional study. The retina was assessed with fundus photography using a Topcon DRI OCT Triton (Topcon Corp., Tokyo, Japan) in the COVID-19 unit. Genotyping of selected polymorphisms in the genes for ACE (rs4646994), ACE2 (rs2285666), and AGTR2 (rs1403543) was performed. The COVID-19 group was divided into mild (n = 12) and severe (n = 57), and then further divided according to the presence of COVID-19 retinopathy (Yes, n = 50;No, n = 19). The presence of the AGTR2 rs1403543-AA genotype was associated with a 3.8-fold increased risk of COVID-19 retinopathy (p = 0.05). The genotype frequencies of selected gene polymorphisms were not significantly associated with either the presence of COVID-19 or its severity. This is the first study demonstrating a borderline association of the AGTR2 rs1403543-AA genotype with COVID-19 retinopathy in males;hence, the AGTR2 rs 1403543 A allele might represent a genetic risk factor for COVID-19 retinopathy in males.