Analysis of Microvasculature in Children Recovered from COVID-19 Using Swept-Source OCT/OCTA Technology.

PURPOSE: To analyze structural and vascular changes of the retina and choroid in pediatric patients with coronavirus disease 2019 (COVID-19) using optical coherence tomography (OCT)/OCT angiography (OCTA). METHODS: This comparative cross-sectional study consists of the COVID-19 group including pediatric COVID-19 patients and the control group including healthy children. Vessel density (VD), central macular thickness,, and choroidal thickness (ChT) measurements were performed using swept-source OCT/OCTA 12 weeks after the recovery from COVID-19. RESULTS: The mean VD measurements in the central fovea and nasal quadrants of all three retinal layers and choriocapillaris showed insignificantly lower values in the COVID-19 group when compared to the control group (0:002 < p < 0:05 for all). Similar to VD measurements, insignificant lower ChT measurements were obtained in the central fovea and nasal points in the COVID-19 group. CONCLUSION: OCTA can be used as a non-invasive and valid biomarker in the assessment of early microvascular dysfunction associated with COVID-19.

Long-Term Effect of SARS-CoV-2 Infection on the Retinal and Choroidal Microvasculature.

The purpose of this study was to evaluate the persistent changes in microvascular parameters based on optical coherence tomography angiography (OCTA) in patients hospitalized due to COVID-19 bilateral pneumonia. The case-control prospective study was carried out among 49 patients with COVID-19 and 45 healthy age- and gender-matched 2 and 8 months after hospital discharge. We found a significantly decreased vessel density (VD) in superficial capillary plexus (SCP) in COVID-19 patients. Significantly decreased vessel density (VD) in the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and choriocapillaris (CC), with significantly increased vessel density observed in the choriocapillaris in the foveal area (FCC). The foveal avascular zone in DCP (FAZd) was significantly increased in the COVID-19 group. We found differences between OCTA parameters according to gender. The foveal VD in SCP and DCP was significantly decreased in women compared to men. The FAZ area in SCP (FAZs) and superior VD in the choriocapillaris (SCC) were significantly increased in women. In conclusion, we noticed persistent changes in the ocular parameters of OCTA in COVID-19 patients. At the second follow-up visit, we observed a widened FAZ zone in SCP and decreased VD in some regions of the retina and choroid.

The role of vascular density in pulmonary rehabilitation of PASC patients

Background: Patients suffering from Post-Acute Sequelae of SARS CoV-2 (PASC) infection may benefit from a pulmonary rehabilitation program (PRP). However, patients respond differently to the protocols. Treatment selection based on sensitive endpoints remains arbitrary. Can quantitative CT play a role in providing a safe, effective PRP? Methods: Two patients admitted for PRP were tested. A low dose quantitative CT scan was taken. Functional respiratory imaging (FRI) was performed on the scans. FRI, Lung function and blood vessel analysis were used for clinical decision making in treatment protocol. Result(s): At visit 1, patient 1 showed a significant decrease in small blood vessel volume and increased volume for the larger vessels (fig 1). This vascular redistribution resulted in cardiac disturbances. Therefore, patient 1 was treated with corticosteroids. Patient 2 showed no deviations on the proportion of blood volume in vessels with a cross-sectional area between 1.25 and 5mm2 (BV5%) and enrolled in the PRP. Patients were re-evaluated after 3 months. Patient 1 improved significantly, recovered, and showed normalized results in BV5%. In Patient 2 V02max changed from 1728 to 2738 ml/min from 52% to 84% predicted. Conclusion(s): Vascular density endpoints as BV5% can be considered as identifier for selection of patient for a PRP in long-COVID, and potentially other pathologies. Once normalized, patients can safely enroll in a PRP.

Macular optical coherence tomography angiography analysis in diabetes mellitus patients with a history of Covid-19.

PURPOSE: There is evidence of decreased vessel density in optical coherence tomography angiography (OCTA) after Covid-19. We aimed to investigate whether the outcome of retinal vasculopathy would be worse if patients with diabetes mellitus (DM) were infected with coronavirus using OCTA to assess retinal vessels. METHODS: One eye of each subject was included in the study. Diabetic patients without retinopathy and non-diabetic controls were divided into four groups according to their Covid-19 history: group 1=DM(-)Covid-19(-); group 2=DM(+)Covid-19(-); group 3=DM(-)Covid-19(+); and group 4=DM(+)Covid-19(+). All Covid-19 patients were not hospitalised. Macular OCTA scans were performed in a 6 × 6 mm area. RESULTS: Diabetes had no effect on the area of the foveal avascular zone (FAZ), but Covid-19 caused an increase in FAZ area. Diabetes and Covid-19 had an effect on both the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) in the fovea. Eta squared (ƞ2) is a measure of effect size. The effect size of Covid-19 (ƞ2=0.180) was found to be greater than that of diabetes (ƞ2=0.158) on the SCP, whereas the effect size of diabetes (ƞ2=0.159) was found to be greater than that of Covid-19 (ƞ2=0.091) on the DCP. CONCLUSIONS: The percentage of vessel density was lower in the fovea and the FAZ area was enlarged in the diabetic patients who recovered from Covid-19. In diabetic patients Covid-19 may lead to deterioration of vascular metrics.

Choroidal and Retinal Vascular Findings in Patients with COVID-19 Complicated with Pneumonia: Widefield Imaging.

PURPOSE: The purpose of this study was to analyze choroidal and retinal vascular alterations of both the macula and midperiphery areas in patients hospitalized for COVID-19 infection complicated with pneumonia within 30 days from discharge. METHODS: A total of 46 eyes of 23 subjects with a history of symptomatic COVID-19 infection and recent hospitalization for pneumonia were enrolled in this observational study. Patients had not been previously vaccinated against COVID-19. A group of patients homogenous for age and sex was enrolled as controls. Microvascular retinal and choroidal features of the enrolled patients were studied with widefield optical coherence tomography angiography (OCT-A). Perfusion parameters in terms of the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the choroidal vascularity index (CVI) on enhanced depth imaging (EDI) mode OCT scans were analyzed. RESULTS: Our cohort of patients showed a trend of reduction in VD, significantly in the SCP VD of the superior and inferior midperiphery sectors, whereas the CVI did not show significant differences between the cases and controls. Moreover, a positive correlation between CVI and vessel density in the deep capillary plexus in the macular area (VD-DCP-MAC) was found. CONCLUSION: The systemic disease due to COVID-19 can also involve the retina and choroid with multiple mechanisms: ischemic and inflammatory. Our study showed changes in perfusion occurring in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to the vaccines. There is still the need to better comprise how long COVID-19 actually affects vascular changes in the eye.

The effect of various types of COVID-19 vaccines on the retinal microvasculature.

PURPOSE: To detect the effect of various types of COVID-19 vaccine on macular and optic disc microvasculature. METHOD: One hundred subjects receiving various types of COVID-19 vaccine (AstraZeneca, Sinopharm, Sinovac, Pfizer, and Moderna) were included in this study. A complete ophthalmic examination was done which included best-corrected visual acuity measurement, slit-lamp biomicroscopy, intraocular pressure measurement with Goldmann applanation tonometry, and fundus examination. Optical coherence tomography angiography (OCT-A) was done before and 1 week after receiving the vaccine. Superficial and deep macular capillary densities were measured in the form of the whole image, fovea, parafoveal, and perifoveal capillary density. Optic disc vessel density in the form of the whole disc, inside disc, and peripapillary were also measured. RESULTS: The superficial macular vessel densities, (whole image, fovea, parafoveal, and perifoveal) showed statistically non-significant changes with P-values (0.269, 0.167, 0.346, and 0.476) respectively. Also, the deep macular vessel densities showed statistically non-significant changes with P-values (0.491, 0.096, 0.724, and 0.386) for the whole image, fovea, parafoveal, and perifoveal respectively. Moreover, RPC (radial peripapillary capillary) density showed no significant changes either (the whole disc, inside disc, or peripapillary) with P-values (0.807, 0.141, 0.883) respectively. CONCLUSION: Various types of COVID-19 vaccines had no statistically significant effects on macular or optic disc microvasculature.

Optical Coherence Tomography Angiography Parameters of the Retina in SARS-CoV-2 Recovered Subjects.

INTRODUCTION: This study aims to evaluate retinochoroidal optical coherence tomography angiography (OCTA) parameters in patients recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This study was an observational study that included 80 subjects being discharged after having negative reports on the reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 to evaluate OCTA parameters of the retina. The subjects underwent an ophthalmic evaluation that included best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision (CV), contrast sensitivity (CS), and optical coherence tomography (OCT) parameters. OCTA was done for all patients and was evaluated for foveal avascular zone (FAZ) area, perimeter, and circularity index, and vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retina chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) using 3 x 3 mm scans. The OCTA parameters were compared with normative data of the Indian population for various parameters in question. RESULTS: The subjects included 54/80 (67.5%) males and 26/80 (32.5%) females having a mean age of 52.40 ± 15.71 (18-60) years. The systemic evaluation revealed 38.75% of subjects had hypertension, 30% had diabetes, 20% had kidney disease, 5% had tuberculosis, and 3.75% had coronary artery disease. The mean distance BCVA was logarithm of the minimum angle of resolution (LogMAR) (1.17 ± 0.22), mean IOP was 17.0 ± 4.0 mmHg, mean CS was 2.13 ± 0.36, 50.62% of subjects had normal CV on Farnsworth test while 47% had tritanopia, and none of the subjects had red-green CV defect on Ishihara plates. The OCT scan was normal in 90% of eyes while the posterior vitreous detachment was seen in 4% of eyes, broad vitreomacular adhesion in 2.5% of eyes, and the globally adherent epiretinal membrane was seen in 2.5% of eyes. The mean central macular thickness (CMT) measured 245.14 ± 28.41 micrometers. The mean FAZ area measured 0.37 ± 0.15 mm2, the perimeter was 3.28 ± 1.08 mm, and the circularity index measured 0.41 ± 0.10. The average VD in SCP measured 16.06 ± 12.29, in DCP measured 9.11 ± 8.75, in OR measured 6.38 ± 7.37, in ORCC measured 42.53 ± 12.46, in CC measured 25.83 ± 16.31, and in C measured 25.52 ± 17.49. The VD in coronavirus disease 2019 (COVID-19) subjects was significantly lesser than that in the healthy Indian population in all layers except ORCC. CONCLUSIONS: The SARS-CoV-2 recovered subjects have a reduced VD in retinochoroidal layers from COVID-19, an underlying systemic disease, or both. The CS values fall within normal limits. Several subjects show tritanopia on the Farnsworth test but no red-green CV defect on Ishihara plates.

Persistent dyspnea in post-COVID patients in the absence of pulmonary embolism: added value of lung perfusion scintigraphy

Aim/Introduction: While there's a wide literature on Computed Tomography (CT) abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy has been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism (PE), presenting persistent dyspnea (post-COVID). We compared perfusion scintigraphy and CT findings of post-COVID patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (non-COVID). The correlation between lung perfusion scintigraphy findings and 1) CT abnormalities and 2) clinical/biochemical parameters were also assessed. Material(s) and Method(s): 18 post-COVID and 20 non-COVID patients who underwent lung perfusion scintigraphy and chest high-resolution CT for dyspnea from March 2020 to April 2022 were retrospectively enrolled. From lung perfusion scintigraphy images, counting rates for upper, middle, and lower fields were normalized for the total lung counts to calculate the corresponding ratios (UTR, MTR, and LTR, respectively). CT images were analyzed using a semiautomated segmentation algorithm of 3DSlicer (www.slicer. org), obtaining total, emphysematous, infiltrated and collapsed volumes, normalized for the total lung volumes. Similarly, blood vessel's volumes were collected to compute the vascular density. White blood cells (WBC) count, PT, INR, PTT and D-dimer of both groups, and the infection duration of post-COVID patients were collected from clinical records and blood tests performed before the lung perfusion scintigraphy. Result(s): At the per lung analysis, post-COVID patients with persistent dyspnea showed reduced LTR (24.67>5.08) and higher MTR (52.51>5.22) compared to non-COVID patients (29.85>5.05 and 46.66>3.94, respectively;p<0.0001 for both), while UTR resulted bilaterally superimposable between the two groups. At CT imaging, the rates of emphysematous, infiltrated and collapsed volumes and the vascular density were bilaterally similar in both groups. In post-COVID patients, LTR correlated with the percentage of emphysematous (r=0.498;p<0.01), infiltrated (r=-0.464;p=<0.01) and collapsed (r=-0.463;p<0.01) lungs, while no significant correlations were observed between LTR and CTderived volumes in non-COVID subjects. There was no correlation between lung perfusion scintigraphy parameters with infection duration in post-COVID, WBC, and coagulation biomarkers in both groups. Conclusion(s): Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in post-COVID patients with persistent dyspnea without pulmonary embolism. This phenomenon is correlated with structural lung modifications, including lung parenchymal emphysema, infiltration and collapse, and is independent of infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, pulmonary non-thrombotic microvascular and endothelial dysfunction may be involved.

Optical coherence tomography-based assessment of macular vessel density, retinal layer metrics and sub-foveal choroidal thickness in COVID-19 recovered patients.

Purpose: The primary objective of the study was to assess the macular retinal vessel density, subfoveal choroidal thickness, and retinal layer metrics by optical coherence tomography angiography (OCTA), enhanced-depth imaging optical coherence tomography (EDI-OCT), and spectral domain optical coherence tomography (SD-OCT), respectively, in recovered COVID-19 patients and its comparison with the same in control subjects. The secondary objective was to evaluate differences in OCTA parameters in relation with the severity of COVID-19 disease and administration of corticosteroids. Methods: A case-control study was performed that included patients who had recovered from COVID-19 and age-matched healthy controls. Complete ocular examination including OCTA, SD-OCT, and EDI-OCT were performed three months following the diagnosis. Results: Three hundred sixty eyes of 180 subjects were enrolled between the two groups. A decreased mean foveal avascular zone area in both superficial capillary plexuses (P = 0.03) and deep capillary plexuses (P < 0.01), reduced average ganglion cell layer-inner plexiform layer thickness (P = 0.04), and increased subfoveal choroidal thickness (P < 0.001) were observed among cases in comparison to the control group. A significant correlation was found between sectoral macular vessel density in relation to disease severity and a decrease in vessel density with greater severity of the disease. Conclusion: OCTA detected retinal microvascular alterations following SARS-CoV-2 infection in subjects with the absence of any clinical ocular manifestation or systemic thrombotic events. These parameters could be used to help identify patients with a higher incidence of systemic thromboembolism on longer follow-ups and identify the impact of corticosteroids on retinal architecture.

The Effect of Reduced Oxygen Saturation on Retinal Microvascularization in COVID-19 Patients with Bilateral Pneumonia Based on Optical Coherence Tomography Study.

The aim of the study was to evaluate changes in the retinal thickness and microvasculature based on optical coherence tomography (OCT) depending on baseline oxygen saturation (SpO2) in patients hospitalized due to COVID-19 bilateral pneumonia. The prospective study was carried out among 62 patients with COVID-19 pneumonia who underwent ophthalmic examination after hospital discharge. They were divided into three groups depending on the oxygen saturation (SpO2) on admission: ≤90% (group 1), >90% and ≤95% (group 2), and >95% (group 3). The following parameters were assessed in the ophthalmological examination and correlated with the baseline SpO2: ganglion cell layer (GCL), the retinal nerve fiber layer (RNFL) in the macular area, RNFL in the peripapillary area, the foveal avascular zone (FAZ) in superficial capillary plexus (SCP) and deep capillary plexus (DCP), vessel density (VD) in SCP, in DCP, and in the choriocapillaris plexus (CC). Baseline saturation ≤90% in COVID-19 patients caused a decrease of VD in some areas of SCP and DCP and an increase in FAZ area in SCP and DCP. In the group of patients with SpO2 ≤ 90% statistically significant thinning of the retina in the inner superior ring (ISR) (p = 0.029), the inner temporal ring (ITR) (p = 0.34), the outer superior ring (OSR) (p = 0.012), and the outer temporal ring (OTR) (p= 0.004)] was observed. The statistically significant thickening of RNFL optic disc and thinning of RNFL retina in some macular areas in patients with SpO2 ≤ 90% were reported. The size of FAZ area in SCP and vessel density were significantly greater in some areas of SCP, DCP, and CC in patients with SpO2 ≤ 90% (p = 0.025). Baseline oxygen saturation ≤90% has been found to influence the ocular parameters of OCT in COVID-19 patients. We noticed a widened FAZ zone in SCP and increased VD in some regions of the retina and choroid as a response to systemic hypoxia.

Evaluating retinal microvascular changes in COVID-19 using wide-field swept-source optical coherence tomography angiography

Purpose : The effects of COVID-19 on the retina have been debated since the start of the pandemic. This study aims to assess how COVID-19 may alter retinal microvasculature using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). Methods : This prospective, cross-sectional, observational study included patients with a positive COVID-19 polymerase chain reaction (PCR) test who underwent WF SS-OCTA imaging from August 2020 to November 2021. The mean days from PCR diagnosis to imaging was 175.6. Age-matched controls included healthy eyes and fellow eyes of retinal detachment, retinal tears, retinal artery occlusion, and retinal vein occlusion. Patients with diabetes, uncontrolled hypertension, retinal disease, prior retinal surgery, and a positive COVID-19 test >365 days before imaging were excluded. Vessel density (VD) and vessel skeletonized density (VSD) were calculated (Macular Density Algorithm v0.7.3.3, ARI Network) for the superficial capillary plexus (SCP), deep capillary plexus (DCP), and whole retina using 3x3, 6x6, and 12x12 mmscans centered on the fovea. A mixed-effect multivariate multilevel linear regression model was used to identify any difference between controls and COVID-19 groups. Results : 34 eyes of 29 patients with COVID-19 and 54 eyes of 45 controls were included. Generalized reductions in VD and VSD were seen in COVID-19 eyes compared to controls (Fig 1). Controlling for age, COVID-19 was associated with a statistically significant overall reduction in VD in the SCP and whole retina in 3x3 mmand DCP of 6x6 mm scans as well as decreased VSD in the DCP in 6x6 mm scans(Table 1). Looking at changes by region, COVID-19 eyes had significant reductions in superior sectors in VD across all scan sizes and layers except the whole retina in 6x6 mm scans, and in VSD across all scan sizes and layers except the SCP in 3x3 and 6x6 mm scans and whole retina in 6x6 mm scans. Additional region-specific reductions in VD and VSD were seen in the DCP in 6x6 and 12x12 mm scans, whole retina in 12x12 mmscans, and SCP in 12x12 mmscans. Conclusions : Patients with COVID-19 showed reduced VD and VSD compared to controls. This may indicate that there are some retinal microvasculature changes in patients with prior COVID-19 infection. (Figure Presented).

Possible Impact of functional active GPCRautoantibodies on retinal microcirculation in Long-COVID

Purpose : Long-COVID is assumed to have an autoimmune component. As a seropositivity of functional active autoantibodies against G-protein coupled receptors (GPCR-AAb) and an impaired retinal microcirculation, measured by OCT-angiography (OCT-A), was observed after COVID-19 infection, it was the aim of the present study to investigate the impact of GPCR-AAbs on retinal microcirculation in patients with LongCOVID. Methods : Seventy-six patients with Long-COVID (COVID-19 infection was confirmed by real time rt-PCR) were recruited. A seropositivity for GPCR-AAbs (Nociceptin-AAb, ß2-AAb, AT1-AAb, α1-AAb, MAS-AAb, M2-AAb, ETA-AAb) was analyzed by a specific rat cardiomyocyte bioassay in vitro. Macular (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) and peripapillary vessel density (VD) were measured by OCT-A (Spectralis II, Heidelberg, Germany). VD analysis was done by the Erlangen-Angio tool, including an APSifyed and Bruch's membrane opening (BMO) based analysis. Data were analyzed by mixed model (SAS version 9.4). Gender and age were set as covariates. The study was approved by the local ethics committee and was done in accordance with the tenets of the Declaration of Helsinki. Informed consent was achieved. Results : All patients with Long-COVID showed a seropositivity for GPCR-AAbs (100%). Female patients with Long-COVID showed lower macular and peripapillary VD compared to men. A significant effect of a seropositivity of AT1-AAb on age-corrected least squares means (LS-means) overall VD of DCP ([CI: 0,25;6.07], p=0.03). A seropositivity of α1-AAb showed a significant effect on age-corrected LS-mean overall VD of SVP ([CI: 0.07;2.69], p=0.04), of DCP ([CI: 0.36;3.25], p=0.01), and of PH ([CI: 1.17;5.59], p=0.01), respectively. A seropositivity of MAS-AAb yielded a significant effect on age-corrected LS-mean overall VD of DH (CI: 1.48;6.07, p=0.001). A seropositivity of ß2-AAb has a significant effect on agecorrected LS-mean overall VD of MH (CI: 0,02;1,94, p=0.04). For those effects, the covariate age was significant in the type III tests (p<0.05), thus analysis was done considering this age-effect. Conclusions : As autoimmune mechanisms were reported to be involved in the pathogenesis of Long-COVID, we postulate that functional active GPCR-AAb may have an impact on retinal microcirculation, being a propable correlate to systemic disease.

Optical coherence tomography angiography based assessment of macular vessel density, retinal layer metrics and subfoveal choroidal thickness in COVID-19 patients

Purpose : OCTA is a non-invasive imaging technique for assessment of retino-choroidal vasculature. It allows for the quantitative assessment of retinal microvasculature. This study evaluates macular vessel density (VD), foveal avascular zone (FAZ) area, subfoveal choroidal thickness (SFCT) and retinal layer metrics by optical coherence tomography angiography (OCTA) in COVID-19 recovered patients. Additionally we studied the correlation of OCTA parameters with severity and duration of COVID-19 disease, steroid administration, and vaccination status. Methods : It is a case-control study of 180 patients. OCTA parameters namely-superficial and deep VD in various sectors-total, superior, inferior, central, inner, superior-inner, inferior-inner, full;superficial and deep FAZ area;SFCT: central subfield thickness (CST) were measured. Additionally, retinal layer metrics, including nerve fiber layer, ganglion cell layer-inner plexiform complex, inner nuclear layer, outer plexiform layer, and outer nuclear layer were compared between cases and controls. A correlation analysis of OCTA parameters was done with severity and duration of disease. Results : FAZ area (superficial and deep);retinal layer metrics including ganglion cell layer and inner plexiform layer, outer plexiform layer and outer nuclear layer showed significant reduction while there was a significant increase in SFCT in COVID-19 patients. Corticosteroid treatment resulted in significant decrease in VD. A positive correlation was elicited between FAZ area and disease duration;while VD correlated negatively with the duration of disease. Multivariate analysis showed significant relationship between superficial FAZ area, deep FAZ area and SFCT. Conclusions : OCTA showed alteration in retinal microvasculature and metrics in COVID-19 patients. Choroid being a highly vascular structure was also affected. There was a resultant alteration in FAZ area and SFCT. Moreover, thrombotic phenomenon associated with COVID could alter retinal layer metrics. Additionally, corticosteroids also appear to alter retinal microvasculature. This study could help understand the wide-spread thrombotic phenomenon often associated with COVID infection and predisposition for the same among specific patients.

Analysis of Microvasculature in Children Recovered from COVID-19 Using Swept-Source OCT/OCTA Technology.

The choroid is one of the most vascularized regions of the human body. Therefore, various local and systemic physiologic/pathologic conditions and environmental factors have effects on choroidal thickness.

Optical Coherence Tomography Angiography Analysis of Vessel Density Indices in Early Post-COVID-19 Patients.

Purpose: A hypercoagulable state has been reported to cause potential sight-threatening ischemia in patients suffering from Coronavirus disease 2019 (COVID-19). This study aimed to determine whether vessel density (VD), as measured by optical coherence tomography angiography (OCT-A), has insights into retinal and choriocapillaris vascular changes in patients affected by SARS-CoV-2 infection. Methods: Hundred and fifty two patients positive for SARS-CoV-2 infection were enrolled in this observational, retrospective, controlled study. A control group of 60 healthy subjects was selected for statistical comparisons. Raw OCT and OCT-A data were exported and 3D datasets were analyzed to determine VD. Results: Hundred and forty eyes (92.1%) were included for final analysis. The VD of the superficial capillary plexus (SCP) did not differ between the two groups. The mean VD of the deep capillary plexus (DCP) and the choriocapillaris (CC) was significantly lower in the foveal sector of the COVID-19 group compared to healthy controls. Within the post-COVID-19 group, the lowest DCP and CC foveal VD values were recorded in patients treated with antiviral therapy; no differences were observed among COVID-19 patients with other comorbidities (hypertension, diabetes, thyroid disease) or taking antiplatelet therapy. DCP and CC foveal VD were significantly lower in patients hospitalized in an intensive care unit (ICU) than asymptomatic patients. Conclusion: Foveal vessel density at the level of DCP and CC was reduced in post-COVID-19 patients. Further studies evaluating these changes over time will be needed to corroborate the hypothesis of a microvascular retinal impairment in individuals who have recently recovered from SARS-CoV-2 infection.

Persistent dyspnea in post-covid patients in the absence of pulmonary embolism: added value of lung perfusion scintigraphy

Background-Aim: While there's a wide literature on CT abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy have been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism, presenting persistent dyspnea (POST-COVID). We compared perfusion scintigraphy and CT findings of these patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (NON-COVID). In POST-COVID patients, the correlation between lung perfusion scintigraphic findings and (1) CT abnormalities, and (2) clinical/ biochemical parameters were also assessed. Methods: 24 POST-COVID and 33 NON-COVID patients who underwent lung perfusion scintigraphy for dyspnea from March 2020 to December 2021 were retrospectively enrolled. High-resolution chest CT performed 15 days before/after lung perfusion scintigraphy were available in 15/24 POST-COVID and 15/33 NON-COVID patients. From scintigraphic images counting rates for upper, middle, and lower fields were calculated in order to compute their ratio with total lung counts (UTR, MTR, and LTR, respectively) for both right and left lungs (RL and LL, respectively). CT images were analyzed using a semi-automated segmentation algorithm of 3D Slicer ( http://www.slicer.org), obtaining total, infiltrated and blood vessels' volumes, in order to calculate the infiltration rate (IR) and vascular density (VD). White blood cells, platelets, PT, INR, PTT, fibrinogen, and D-dimer of 15/24 POST-COVID patients were also collected from blood tests performed before the lung perfusion scintigraphy. Results: POST-COVID patients with persistent dyspnea showed reduced LTR (RL 22.4% ± 6.6%;LL 24.7% ± 3.1%) and higher MTR (RL 55.2% ± 5.2%;LL 49.1% ± 3.3%) compared to non- COVID patients (RL-LTR 29.6% ± 6.0%, p<0.0001;LL-LTR 28.3% ± 4.6%, p = 0.001;RL-MTR 47.3% ± 4.2%, p<0.0001;LL-MTR 47.3% ± 3.0%, p = 0.036), while UTR resulted bilaterally superimposable between the two groups. Similar IR and VD values at CT imaging were documented bilaterally in both groups. In POSTCOVID patients, no significant correlations between lung perfusion scintigraphy and CT findings were observed. Correlation analysis indicated D-dimer levels as associated with UTR (Pearson's r = 0.664;p = 0.007) and MTR (Pearson's r = - 0.555;p = 0.032), while no parameter significantly associated with LTR was observed. Conclusions: Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in POST-COVID patients with persistent dyspnea in the absence of pulmonary embolism, independently from CT abnormalities, infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, lung nonthrombotic microvascular and endothelial dysfunction may be involved.

Retinal microvascular morphology versus COVID-19: What to anticipate?

BACKGROUND: To investigate retinal microvascular morphological changes in previously COVID-19 infected patients using optical coherence tomography angiography (OCTA), and compare the findings to age- and gender-matched healthy subjects. METHODS: In this cross-sectional study, OCTA findings (6.0 × 6.0 mm scan size and scan quality index ≥7/10) from previously COVID-19 infected patients (group 1, 32 patients, 64 eyes) with ≥1 month of complete recovery were compared to healthy subjects (group 2, 33 subjects, 66 eyes) with no history of COVID-19 infection. A positive real-time reverse transcription-polymerase chain reaction test on a naso-pharyngeal swab sample confirmed the diagnosis. The AngioVueAnalytics, RTVue-XR 2017.1.0.155 software measured and recorded OCTA parameters. RESULTS: Group 1 had significantly lower superficial capillary plexus vessel densities in all foveal regions than group 2 (P<0.05). Foveal deep capillary plexus vessel density in group 1 was also significantly lower than in group 2 (P=0.009); however, no significant differences were found in other regions (P>0.05). All foveal avascular zone (FAZ) parameters were higher in group 1 than in group 2, with significant differences in FAZ area (P=0.019) and foveal vessel density 300 µm area around FAZ (P=0.035), but not FAZ perimeter (P=0.054). The outer retina and choriocapillaris flows were significantly lower in group 1 than in group 2 (P<0.05). CONCLUSIONS: Prior COVID-19 infection seems to be associated with significant changes in retinal microvascular density, as well as FAZ and flow parameters, which may be attributed to different pathogenic mechanisms that lead to SARS-CoV-2 infection, such as thrombotic microangiopathy and angiotensin-converting enzyme 2 disruption.

Retinal microvascular impairment in COVID-19 patients: A meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic in an unprecedented time frame. Systemic vascular involvement in COVID-19 has been identified, and SARS-CoV-2 has also been found to cause multiple organ ischemia and posterior ocular segment disease in mammals, raising concerns about the human retinal microvascular involvement in SARS-CoV-2. OBJECTIVE: To objectively assess the presence of retinal microvascular impairment in COVID-19 patients by optical coherence tomography angiography (OCTA), so as to facilitate the clinical system management of COVID-19 patients. METHODS: We searched PubMed, Cochrane Library, EMBASE, Ovid, CBM to collect eligible studies. The main outcomes included the vessel density (VD), area or perimeter of foveal avascular zone (FAZ), central foveal thickness (CFT), subfoveal choroidal thickness (SCT) in our meta-analysis. RESULTS: We eventually included five studies with a total of 401 participants. Our meta-analysis showed that nonacute infectious COVID-19 or post-COVID-19 patients presented significantly lower foveal VD of deep capillary plexus (WMD = -4.22, 95% CI [-8.00, -0.43]) and thinner SCT (WMD = -10.33, 95% CI [-19.08, -1.57]) than healthy controls. The foveal VD and parafoveal VD of superficial capillary plexus, parafoveal VD of deep capillary plexus, CFT, area, and perimeter of FAZ showed no significant differences between the groups. CONCLUSION: The patients of nonacute infectious COVID-19 or post-COVID-19 displayed alterations in the retinal microvasculature and choroidal vessels, including a significantly lower foveal VD in deep capillary plexus and thinner SCT. The impairment may be a medium to long-term process. Close ophthalmic surveillance is necessary for COVID-19 patients or post-COVID-19 patients.

Ocular sequelae in severe COVID-19 recovered patients of second wave.

Purpose: To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. Methods: In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. Result: The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). Conclusion: Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.

Analysis of swept-source optical coherence tomography angiography measurement alterations in adult patients recovered from COVID-19.

CLINICAL RELEVANCE: Vessel density (VD) measurements obtained using swept-source optical coherence tomography angiography (SS-OCTA) of the retinal layers and choriocapillaris have the capacity to demonstrated retinal changes in COVID-19 patients. BACKGROUND: To investigate VD changes in the retinal layers and choroid using SS-OCTA in patients recovered from COVID-19. METHODS: This cross-sectionally designed study was conducted in a single eye centre. The diagnosis of COVID-19 disease was confirmed by a polymerase chain reaction test. Patients who had fully recovered from COVID-19 served as the COVID-19 group, and the control group comprised age- and gender-matched healthy subjects. VD measurements in the superficial and outer retina layers and the choriocapillaris were performed using SS-OCTA. RESULTS: VD measurements in the central fovea and all quadrants of superficial and deep retinal layers, and the choriocapillaris, showed a significant decrease in the COVID-19 group (P < 0.05 for all) compared to the control group. Significant reductions in VD measurements were more prominent in the choriocapillaris when compared to the retinal layers. Mean ferritin and C-reactive protein (CRP) concentrations showed negative correlations with VD measurements in certain quadrants of the deep retinal layer and choriocapillaris. CONCLUSION: VD reductions occur the superficial and deep retinal layers and choriocapillaris in patients with pre-existing COVID-19. These results suggested the use of SS-OCTA as a microvascular biomarker and an auxiliary technique for the diagnosis and follow-up of COVID-19.