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.

Evaluation of the retina with optical coherence tomography angiography (OCTA) in patients with coronavirus (COVID-19) infection.

PURPOSE: The goal of this study is to compare the optical coherence tomography angiography (OCTA) findings in Coronavirus (COVID-19) positive adult and pediatric patients with those of healthy volunteers with the same demographic characteristics. METHODS: The right eye of 157 adults infected with covid, 168 healthy adult volunteers, 40 children (6-18 years of age) infected with covid, and 44 healthy children (6-18 years of age) were included in this prospective study. All participants underwent ophthalmological examination and OCTA. The OCTA findings were evaluated. RESULTS: Deep nasal density (DND), deep inferior density (DID), and deep parafoveal density (DPD) were significantly lower in the pediatric covid-affected group (PCAG) than in the pediatric healthy control group (PHCG) (P=0.034, P=0.029, P=0.022 respectively). On the other hand, radial peripapillary capillary vessel density (RPCVD) intra-disc measurements were significantly higher in the PCAG compared to the PHCG (P=0.025). There was no significant difference between the OCTA measurements of the adult covid-affected group (ACAG) and the adult healthy control group (AHCG). CONCLUSION: In our study, significant differences were found in OCTA measurements between the covid group and the healthy control group in children. Retinal microvascular changes may occur in patients with covid infection, and these patients might be followed for long-term retinal changes.

Morphovascular changes after anti-VEGF intravitreal injection for a choroidal neovascularization secondary to COVID-19 infection in a pediatric patient.

Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy. Although the incidence of CNV is quite rare in children and adolescents, these lesions have a severe impact on visual acuity and quality of life over patients' lifetime. The management of CNV in pediatric patients is challenging, clear guidelines are limited due to a lack of randomized clinical trials. However, the more promising option is the use of vascular endothelial growth factor (VEGF) inhibitors. We reported a case of recurrent idiopathic choroidal neovascularization in a healthy pediatric patient after COVID 19 infection. Optical coherence tomography angiofraphy (OCTA) showed, in a non invasive way, a choroidal neovascularization at the posterior pole including macula and superior temporal arcade in the right eye, while the left eye was unaffected. In order to inactivate the neovascularization, intravitreal injections of anti-VEGF (Lucentis-Ranibizumab 0.3 mL) were performed in the right eye. Six months after the injections BCVA of the right eye was improved from 0.7 logMAR to 0.2 logMAR. OCT-A examination did not detect any signs of attivation of the preexistent neovascularization. It is reasonable to assert that Anti-VEGF could be the main treatment in case of choroidal neovascularization in young patients after COVID 19 infection due to the high chorioretinal level of VEGF-A described in these diseases.

Early effects of inactivated (CoronaVac) SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density.

AIMS: We aimed to investigate the early effects of inactivated SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density in healthy subjects. METHODS: Thirty-four eyes of 34 healthy volunteers who received the CoronaVac (Sinovac Life Sciences, China) were included in this prospective study. Resistive index (RI), pulsatility index (PI) and peak systolic velocity (PSV) of the ophthalmic artery (OA), central retinal artery (CRA), and the temporal and nasal posterior ciliary arteries (PCA) were evaluated with color Doppler ultrasonography (CDUS) before vaccination, at the 2nd and 4th weeks after vaccination. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), foveal avascular zone (FAZ), and choriocapillaris blood flow (CCF) measurements were made using optical coherence tomography angiography (OCTA). RESULTS: When compared to the pre-vaccination values, there was no significant change in OA-PSV, temporal-nasal PCA-PSV, CRA-EDV, temporal-nasal PCA-EDV at 2nd and 4th weeks after vaccination. However statistically significant reductions were found in the OA-RI, OA-PI, CRA-RI, CRA-PI, temporal-nasal PCA-RI, temporal-nasal PCA-PI values, CRA-PSV at post-vaccination 2nd week (p<0.05 for all). While there was sustained reduction in OA-RI, OA-PI, CRA-PSV, and nasal PCA-RI values at 4th week after vaccination, the change in CRA-RI, CRA-PI, temporal PCA-RI, temporal-nasal PCA-PI values were not significant compared to pre-vaccination values. There was no statistically significant difference in the SCP-VD, DCP-VD, FAZ and CCF measurements. CONCLUSIONS: Our findings demonstrating that CoronaVac vaccine did not affect retinal vascular density in the early period, but it caused alterations in the retrobulbar blood flow.

Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARS-CoV-2 Infection (COVID-19) Compared with Healthy Young Controls.

PURPOSE: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). METHODS: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l'Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant's eyes. RESULTS: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group. CONCLUSION: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02-0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues.

Acute macular neuroretinopathy as the first stage of SARS-CoV-2 infection.

INTRODUCTION: To report two cases of Acute Macular Neuroretinopathy (AMN) presented as the first stage of SARS-CoV-2 infection in two European countries during the third wave of pandemic viral infection in the early months of 2021. OBSERVATIONS: A unilateral case of type 1 AMN in a man and a bilateral case of type 2 AMN in an otherwise heathy patients were reported. Sudden onset of paracentral scotoma characterized the cases with no systemic symptoms. Structural optical coherence tomography (OCT) shows multifocal middle and inner retinal hyperreflective infarctions. OCT-Angiography showed the presence of hypoperfusion of the deep capillary plexus (DCP) corresponding to the hyperreflective lesions visible on structural OCT, confirming the diagnosis. CONCLUSIONS AND IMPORTANCE: Type 1 and type 2 AMN may be the first stage of SARS-CoV-2 infection. We suggest testing all patients with AMN for SARS-CoV-2. In our cases, the natural history of AMN associated with SARS-CoV-2 infection was similar to already described cases of AMN.

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.

Evaluation of vascular and perfusional changes in the retina and choroid of children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is hyperinflammation following coronavirus disease 2019 (COVID-19), which affects many organs. The retina and choroid are affected by COVID-19 through microangiopathy and thrombosis but the literature on MISC-C is limited. METHODS: Thirty children (60 eyes) with MIS-C (the study group, or SG) and 32 age-and gender-matched healthy children (64 eyes) (the control group, or CG) were included in the prospective case-control study. Complete ophthalmological examinations, measurements of the vessel densities of the retinal layers, and flow area of the outer retina and choriocapillaris in both groups were conducted with optical coherence tomography angiography (OCT-A). RESULTS: The mean age of the SG was 11.9 ± 3.9 and that of the CG was 12.5 ± 4.6 years (p = 0.197). In this study we found that the vessel density of the deep layer of the inner retina was decreased significantly and was reduced in the outer retina of flow area in the SG in comparison with the CG (p < 0.05, for all). However, there was no significant difference between the groups regarding other measurements. CONCLUSIONS: In MIS-C patients, vessel densities in the deep layer of the inner retina and in the flow area of the outer retina decreased significantly. This OCTA-A finding suggests that MIS-C is related to endothelial thrombotic condition problems in small branches of the retinal artery. The results of this study support the idea that there is a need for screening of MIS-C patients for the presence of these microangiopathic and perfusional complications.

OCTA evaluation of posterior ocular blood flow in patients after COVID-19 infection without pneumonia.

INTRODUCTION: We aimed to demonstrate the changes in optic nerve and retinal microvascular structures with Optical Coherence Tomography Angiography (OCTA) in patients who had COVID-19 infection. METHODS: Prospective study. Retina, choroid and optic nerve head microvascular flow and vascular densities of both groups were measured by OCTA. RESULTS: OCTA measurements of 122 right eyes of a total of 122 patients, including 72 patients in the COVID-19 group and 50 patients in the control group, were included in the study. The Deep Capillary Plexus (DCP) Flow Area (FA) in the COVID-19 group was 1.42±0.23 mm2, in the control group was 1.50±0.15 mm2, Choriocapillary Plexus FA was 1.89±0.04 mm2 in the COVID-19 group, was 1.91±0.05 mm2 in the control group, and a statistically significant difference was found between the two groups (respectively; P=0.03; P=0.02). DCP Whole Vascular density (VD) values were 56.76±4.16% in the COVID-19 group, 58.28±3.88% in the control group; difference between the values was statistically significant (P=0.04). There was no statistically significant difference between the two groups in terms of optic nerve head flow areas and other parameters examined according to quadrants. CONCLUSIONS: Results show that the retinal microcirculation in subjects with mild disease is affected. Even if the disease is mild, patients may need to be followed up for retinal changes that may develop in the future.

Investigation of changes in retinal vascular parameters and choroidal vascular index values during the early recovery period of COVID-19: The COVID-OCTA study.

BACKGROUND: COVID-19 effects microvasculature in many tissues. This study investigated whether the choroidal structure is also affected. METHODS: This cross-sectional study included 80 patients with COVID-19 and the same number of age- and gender-matched healthy individuals. All participants' right eye measurements were examined. Optical coherence tomography angiography (OCTA) was used for imaging. Otherwise, two independent researchers used the Choroidal vascular index (CVI) for choroidal parameters calculation. RESULTS: Superior and deep flow values were lower in the COVID-19 group than in the control group, and vascular density (VD) values were lower in all regions in this group. Except for the superior mean VD, there was no statistically significant difference (p = 0.003). However, the COVID-19 group had significantly lower subfoveal choroidal thickness (SFChT) measurements than the control group (p = 0.001). In addition, no significant difference was observed between the groups in evaluating mean CVI values (p>0.05). CONCLUSION: Noninvasive diagnostic tools such as OCTA and EDI-OCT can be used to monitor early changes in diseases affecting microvessels, such as from COVID-19.

Acute Multifocal Placoid Pigment Epitheliopathy-like Presentation following the First Dose of BNT162B2 COVID-19 Vaccination.

PURPOSE: To report a case with acute posterior multifocal placoid pigment epitheliopathy (APMPPE)-like presentation following the first dose of BNT162b2 COVID-19 vaccination. CASE REPORT: An otherwise healthy 45-year-old woman presented with a headache and blurred vision in her right eye 7 days after the administration of first dose of mRNA (BNT162b2) COVID-19 vaccine. Fundus examination of the right eye revealed multiple discrete yellow-white placoid lesions at the level of deep retinal layers throughout the posterior pole, while left fundus was unremarkable at that time. Swept source-optical coherence tomography (SS-OCT) showed subretinal fluid together with an appearance of bacillary layer detachment at the right macula. A detailed systemic evaluation was carried out without any positive finding. Two weeks after the initial eye examination, similar multiple placoid lesions were observed in her left eye. Fundus lesions almost totally resolved without any treatment bilaterally 5 weeks after the onset of initial symptoms. CONCLUSION: To the best of our knowledge, this is the first report of APMPPE-like presentation described after the BNT162b2 COVID-19 vaccination. Previous COVID-19 vaccination should be kept in mind in the differential diagnosis of APMPPE disease spectrum.

Changes in retinal and choroidal capillary dynamics in patients with multisystem inflammatory syndrome in children.

PURPOSE: To evaluate patients with multisystemic inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using optical coherence tomography angiography (OCTA) during and after resolution of inflammation to investigate the effect of this entity on the retinal and choroidal circulation. METHODS: The study included 38 eyes of 19 patients diagnosed as having MIS-C between March 2021 and June 2021. OCTA measurements of choroidal thickness and vessel density in the radial peripapillary capillary plexus (RPCP), superficial capillary plexus (SCP), and deep capillary plexus (DCP) obtained at time of diagnosis and 60 days later were compared. Correlations between C-reactive protein (CRP) levels at diagnosis and retinochoroidal involvement were investigated. RESULTS: Compared to post-recovery follow-up examinations, patients with active MIS-C showed foveal avascular zone enlargement (p = 0.031), decreased vessel density in the temporal parafoveal SCP (p = 0.047) and all parafoveal areas of the DCP (p < 0.05 for all), and increased choroidal thickness (p = 0.021). Correlation analysis between CRP levels and OCTA changes during MIS-C revealed significant negative correlations with all parafoveal sectors of the SCP and DCP and a significant positive correlation with CT. CONCLUSION: There were especially marked effects on the DCP and choroid in MIS-C patients. Our findings also correlate with CRP levels. The use of optical coherence tomography angiography in patients with multisystemic inflammatory syndrome may have potential future implications for detecting ocular microvascular changes that occur before permanent damage develops. Clinical Trial Registration Number and Date: 77/1340; March 1, 2021.

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.

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.

COVID-19 presenting as a non-arteritic anterior ischemic optic neuropathy.

We present a case of a 61-year-old woman with an atypical non-arteritic anterior ischemic optic neuropathy (NA-AION) as a unique manifestation of COVID-19. Furthermore, the patient worsened after Pfizer-BioNTech COVID-19 vaccine administration. Our findings suggest that NA-AION could result from microangiopathic/thrombotic events that may occur during SARS-CoV-2 infection and/or vaccination against COVID-19. This report sheds light on possible ophthalmologic complications of COVID-19.

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).

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.

Bunazosin inhibited axial elongation with an increase of the choroidal blood perfusion in a murine model of myopia

Purpose : The prevalence of myopia is accelerating worldwide possibly because of the decrease in outdoor activity including COVID-19 home confinement. We have reported the effective treatments of suppressing myopia progression, including oral administration of crocetin (Mori K et al. Sci Rep. 2019) and violet light exposure (Jiang X et al. Proc Natl Acad Sci USA. 2021). In this study, we examined the therapeutic effects of bunazosin, known as one of the α1-adrenergic receptor antagonists, in a lens-induced myopia mouse model. Methods : C57BL/6J mice were induced myopia at 3-week-old by a method established in our research group (Jiang X et al. Sci Rep. 2018). For 3 weeks, mice were equipped with lenses in both eyes, a left for 0 D lens as internal control and a right for -30 D lens as myopia induction. During this period, we administered 0.01% bunazosin hydrochloride solution by intraperitoneal injection (IP group) and eye drop (E group) once a day, and PBS as control. Ocular components including refraction error, axial length, and choroidal thickness before and after myopia induction were measured by an infrared photorefractor and an SD-OCT. The choroidal blood flow was evaluated by an SS-OCT angiography. Results : In the eye with -30D lens of control group, significant changes in a myopic shift of refraction (p < 0.01), axial elongation (p < 0.05), and choroidal thinning (p < 0.01) compared to 0D lens were observed. In contrast, IP or E groups showed no significant difference between both eyes, suggesting myopia progression was suppressed by bunazosin treatment. The choroidal blood flow of the eye with -30D in E group (58.9±8.9%) was higher than that of the control group -30D (44.0±6.4%)(p < 0.05). Conclusions : Bunazosin has a preventive effect on myopia progression by suppressing axial elongation and choroidal thinning together with an increase of choroidal blood flow.

IMPACT of COVID-19 TREATMENTS on PERIPHERAL CAPILLARY DENSITY EVALUATED by NAILFOLD VIDEOCAPILLAROSCOPY

Background: Human SARS-CoV-2 infection can induce a wide spectrum of organ dysfunctions, including microvascular impairment [1]. S1 subunit of viral receptor-binding domain binds to the angiotensin-converting enzyme 2 receptor on endothelium and S2 subunit allows the virus to enter endothelial cells. The resulting breakdown of barrier integrity drives a cascade of infammatory and thrombotic events, that aggravate the course of COVID-19 together with other risk factors [2-4]. Up to date, a lower capillary density has been reported in several distinct body districts, using sublingual video microscopy, ocular optical coherence tomography angiography, skin functional laser Doppler perfusion imaging and nailfold videocapillaroscopy (NVC) [5-8]. NVC examination has been performed in adult COVID-19 patients, however, without a control group [8]. Objectives: To confrm the statistical signifcance of the reduction in capillary density per linear millimeter evaluated by NVC in comparison with primary Ray-naud's phenomenon (PRP) patients and control subjects (CNT) and to evaluate the impact of an aggressive therapy against COVID-19 on the sparing in the number of capillaries. Methods: Sixty-one COVID-19 survivors, thirty-one PRP patients and thirty CNT age and sex-matched underwent NVC analysis. Demographic and clinical data of COVID-19 survivors were collected with special regard to concomitant therapies, that included antivirals, antibiotics, anticoagulants and anti-infamma-tory/immunomodulant drugs (glucocorticoids, hydroxychloroquine, IL-6 receptor antagonist). COVID-19 survivors were divided in two subgroups according to the severity of the active infection: thirty-four survivors with past mild-moderate disease (either unneedy for oxygen supplementation or need for Venturi mask) and twenty-seven survivors with past severe disease (need for Continuous Positive Airways Pressure and/or mechanical ventilation). The same Rheumatologist performed NVC evaluations in all patients and controls, using an optical probe, equipped with a 200x magnifcation lens and connected to a picture analysis software (Videocap, DS Medica, Milan, Italy). Absolute capillary number per linear millimeter was counted. Results: COVID-19 survivors underwent NVC examination after a mean period of 126±53 days from the disease onset. Multivariate analysis showed differences in absolute capillary number per linear millimeter (p<0.001) after adjusting for age, sex, body mass index, comorbidities and concomitant drugs. The mean (± standard deviation) absolute nailfold capillary number per linear millimeter was signifcantly lower in severe (8.2±1.15) and mild-moderate (8.4±0.75) COVID-19 survivors than in both PRP (8.7±0.68) and CNT subjects (9.3±0.53) (p<0.001). The analysis of the impact of treatments on capillary density in the severe COVID-19 patients showed a positive trend (preservation of the capillary number) with antivirals (no: 7.8±1.53;yes: 8.5±0.64;p=0.35) and anti-IL-6 receptor antagonist administration (no: 7.8±1.36;yes: 8.6±0.74;p=0.16), while none of the other drugs was shown to be effective (glucocorticoids p = 0.46;antibiotics = 0.52;anticoagulants not evaluable as they were used in all COVID-19 patients). Conclusion: SARS-CoV-2 infection seems associated to a signifcant capillary loss as distinctive NVC feature and data concerning the comparison of capillary density pre COVID-19 and post COVID-19 are desirable to reinforce this observation. The positive trend in saving the number of capillaries induced by aggressive anti-infammatory therapies in COVID-19 survivors needs larger cohorts of patients.