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.

Structural alterations of the choroid evaluated using enhanced depth imaging optical coherence tomography in patients with coronavirus disease.

PURPOSE: To assess choroidal changes using enhanced depth imaging optical coherence tomography in coronavirus disease (COVID-19). METHODS: Thirty-two patients with moderate COVID-19 and 34 healthy subjects were included in the study. Choroidal thickness was measured at 3 points as follows: at the subfovea, 1500 mm nasal to the fovea, and 1500 mm temporal to the fovea. The total choroidal area, luminal area, stromal area, and choroidal vascular index were measured with Image-J. All the measurements were performed during the disease and at 4 months after remission. RESULTS: In the patient group, the subfoveal, nasal, and temporal choroidal thicknesses were decreased as compared with those in the controls, but without statistically significant differences (p=0.534, p=0.437, and p=0.077, respectively). The mean total choroidal, stromal, and luminal areas and choroidal vascular index were statistically significantly decreased in the patient group (p<0.001, p=0.001, p=0.001, and p=0.003; respectively). At 4 months after remission, the choroidal structural parameters and choroidal vascular index revealed statistically significant increases as compared with the baseline measurements in the patients with COVID-19 (all p<0.001 and p=0.047, respectively). CONCLUSION: The choroidal vascular and stromal parameters showed significant transient decreases during the disease course of COVID-19.

Evaluation of acute effects of pulmonary involvement and hypoxia on retina and choroid in coronavirus disease 2019: An optic coherence tomography study.

PURPOSE: We investigated the acute subclinical choroidal and retinal changes caused by Coronavirus Disease 2019 (COVID-19) in patients with and without pulmonary involvement, using spectral domain optic coherence tomography. METHODS: This prospective case-control study included COVID-19 patients: 50 with pulmonary involvement and 118 with non-pulmonary involvement. All patients were examined 1 month after recovering from COVID-19. The changes were followed using optic coherence tomography parameters such as choroidal and macular thickness and retinal nerve fibre layer and ganglion cell complex measurements. RESULTS: All choroidal thicknesses in the pulmonary involvement group were lower than in the non-pulmonary involvement group and the subfoveal choroidal thickness differed significantly (p=0.036). Although there were no significant differences between the central and average macular thicknesses in the two groups, they were slightly thicker in the pulmonary involvement group (p=0.152 and p=0.180, respectively). A significant decrease was detected in the pulmonary involvement group in all ganglion cell complex segments, except for the outer nasal inferior segment (p<0.05). In addition, a thinning tendency was observed in all retinal nerve fibre layer quadrants in the pulmonary involvement group compared to the non-pulmonary involvement group. CONCLUSION: In COVID-19 patients with pulmonary involvement, subclinical choroidal and retinal changes may occur due to hypoxia and ischemia in the acute period. These patients may be predisposed to ischemic retinal and optic nerve diseases in the future. Therefore, COVID-19 patients with pulmonary involvement should be followed for ophthalmological diseases.

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.

How does Covid-19 affect the choroidal structures at the early post-infectious period?

PURPOSE: To evaluate choroidal thickness (CT) and choroidal vascularity index (CVI) in patients recovered from COVID-19 using enhanced depth imaging optical coherence tomography in the early postinfectious period. METHODS: Sixty-five patients recovered from COVID-19 and 72 healthy subjects were included in the study. A full ophthalmic examination including best-corrected visual acuity (BCVA), slit lamp biomicroscopy, and dilated fundus examination was performed. CT was measured at 3 points as follows: subfoveal, 1000µm nasal and temporal to the fovea. The total choroidal area (TCA), luminal area (LA), stromal area (SA), and CVI were measured with Image-J. RESULTS: The mean age was 39.09±11.27 years in the COVID-19 group and 39.61±11.43 years in the control group. The mean time from the first positive RT-PCR was 49.54±26.82 days (range 18-120) in the COVID-19 group. No statistically significant difference was detected between the groups with regard to axial length, spherical equivalent, and BCVA (all P>0.05). CT was found to be lower in the COVID-19 group compared to the control group in all quadrants, but this difference was not significant (all P>0.05). The mean TCA, LA, and CVI were statistically significantly reduced in the COVID-19 group (all P<0.001); however, SA showed no statistically significant difference (P=0.064). CONCLUSIONS: In asymptomatic or mild COVID-19, CVI and LA decrease significantly, while CT thins in the early postinfectious period but not significantly.

Evaluation of choroidal thickness with OCT in COVID-19 patients with high D-dimer levels.

To evaluate retinal and choroidal thickness with optical coherence tomography (OCT) to detect retinal and choroidal pathologies in coronavirus disease 2019 (COVID-19) patients with high D-dimer levels. Thirty patients who were hospitalized in the intensive care unit due to severe acute respiratory syndrome coronavirus 2 and whose D-dimer levels were high during this period, who applied to the internal medicine outpatient clinic between 15 and 30 days after discharge, and 30 healthy volunteers with similar age and gender as the control group was included in the study. After full ophthalmological examination, central foveal and choroidal thicknesses were evaluated using optical coherence tomography. Statistical analysis of the study data demonstrated that there was no significant difference between the groups in terms of age or gender (p > 0.05). There was also no statistically significant difference between the groups in terms of central foveal thickness, central choroidal thickness, or nasal 500, nasal 1500, temporal 500, or temporal 500 micron distances (p > 0.05 for all parameters). Choroidal and retinal vascular thicknesses were not affected in the short term in COVID-19 patients hospitalized in the intensive care unit.

Retrobulbar ocular blood flow and choroidal vascular changes in patients recovering from COVID-19 infection.

BACKGROUND: To evaluate the effects of COVID-19 infection on the ocular vascular structure including choroidal thickness and retrobulbar blood flow values in comparison with healthy subjects. METHODS: Ninety eyes of 90 patients were included in this study. Participants were divided into Group 1 (n = 30) with mild COVID-19 infection, Group 2 (n = 31) with moderate disease, and Group 3 with age- and sex-matched healthy subjects (n = 29). Choroidal thickness was measured at the subfoveal area and at 500-µm intervals nasal and temporal to the fovea up to a distance of 1500 µm, using the enhanced depth imaging (EDI) technique of spectral coherence tomography (SD-OCT). The peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) values of the central retinal artery (CRA) and ophthalmic artery (OA) were evaluated with color Doppler ultrasonography (CDU). RESULTS: The choroidal thickness was significantly thinner in Group 1 and Group 2 than in Group 3 at all measurement points (p <0.001). This difference was not present between Group 1 and Group 2 who had COVID-19 disease of different severity (p>0.05).Among the retrobulbar blood flow parameters, OA PSV value was significantly lower in Group 1 and Group 2 compared to Group 3 (p = 0.025, p = 0.016, respectively). However, the CRA PSV and EDV and OA EDV values, and the CRA and OA PI and RI values were not statistically different between the groups (p> 0.05). CONCLUSION: COVID-19 infection may predispose patients to ocular vascular pathologies by affecting both choroidal and retrobulbar blood flow.

Strong ACE-2 expression in the choroidal vessels: do high choroid plexuses serve as a gateway for SARS-CoV-2 infection on the human brain?

OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2.  The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a  strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.

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.

Change in retinal vessel diameter and choroidal thickness in patients with severe COVID-19: Change In Retinal Parameters In Patients With Severe COVID-19.

PURPOSE: To compare the differences in retinal vascular structure and choroidal thickness between the active disease and post-recovery periods in COVID-19 patients and healthy controls. MATERIAL AND METHODS: This prospective, cross-sectional study included 30 eyes from 30 patients with severe COVID-19 and 30 eyes of 30 sex-matched healthy controls. Central macular thickness (CMT), subfoveal choroidal thickness (CT) and retinal vascular changes of patients were measured after positive polymerase chain reaction (PCR) (where the patient had COVID-19-related symptoms) and then three months after two negative PCRs. Laboratory parameters, including C-reactive protein and d-dimer levels, were also recorded. RESULTS: The mean age of the patients was 47.90 ± 9.06 years in patients group, 49.07 ± 8.41 years in control goups (p = 0.467). In terms of choroidal thicknesses subfoveal, nasal and temporal region were significantly higher in the active disease period than control group (p = 0.019, p = 0.036, p = 0.003, respectively). When the after recovery period was compared with the control group in terms of choroidal thickness, although the choroidal thickness was higher in all regions, this difference was not found statistically significant. There was no statistically significant difference in CMT between groups (p = 0.506).The mean venous and arterial wall thicknesses were significantly higher in the active period than after recovery (p = 0.023, p = 0.013, respectively) but there were no differences between after recovery and control groups in the pairwise comparison (p = 0.851, p = 0.715, respectively). CONCLUSION: In patients with severe COVID-19, there are changes in thickness of the choroid and retinal vessel walls. While vascular wall thickness increases due to inflammation, the absence of lumen changes may be associated with hemodynamic variables.

How are central foveal and choroidal thickness affected in patients with mild COVID-19 infection?

The aim of this study was to evaluate the effects of  COVID-19 on central foveal and choroidal thicknesses. Thirty-two patients with a positive SARS-CoV-2 PCR test who received outpatient treatment within the previous two months and 32 healthy controls were included in the study. Patients requiring hospitalization due to COVID-19 as well as the patients who received either intensive care support and/or antiplatelet therapy, smokers, or patients with systemic or ocular diseases were excluded from the study. After full ophthalmological examination, central foveal and choroidal thicknesses were evaluated by using optical coherence tomography. Statistical analysis of the study data demonstrated no significant difference between the groups in terms of age or gender (p>0.05). There was also no statistically significant difference between the groups in terms of central foveal thickness, central choroidal thickness, or nasal 500, nasal 1500, temporal 500, or temporal 500-micron distances (p>0.05 for all parameters). Choroidal and retinal thicknesses were not affected in patients with recent mild COVID 19 without comorbidities.

Histopathological assessments reveal retinal vascular changes, inflammation, and gliosis in patients with lethal COVID-19.

PURPOSE: The purpose of this study is to assess for histopathological changes within the retina and the choroid and determine the long-term sequelae of the SARS-CoV-2 infection. METHODS: Eyes from seven COVID-19-positive and six similar age-matched control donors with a negative test for SARS-CoV-2 were assessed. Globes were evaluated ex vivo with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for Epon embedding and immunocytochemistry. RESULTS: Fundus analysis shows hemorrhagic spots and increased vitreous debris in several of the COVID-19 eyes compared to the controls. OCT-based measurements indicated an increased trend in retinal thickness in the COVID-19 eyes; however, the difference was not statistically significant. Histology of the retina showed presence of hemorrhages and central cystoid degeneration in several of the donors. Whole mount analysis of the retina labeled with markers showed changes in retinal microvasculature, increased inflammation, and gliosis in the COVID-19 eyes compared to the controls. The choroidal vasculature displayed localized changes in density and signs of increased inflammation in the COVID-19 samples. CONCLUSIONS: In situ analysis of the retinal tissue suggests that there are severe subclinical abnormalities that could be detected in the COVID-19 eyes. This study provides a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 infections to further understand the long-term effects caused by this virus.

Evaluation of choroidal thickness in patients who have recovered from COVID-19.

PURPOSE: We aimed to evaluate choroidal thickness (CT) in patients who have recovered from COVID-19 by using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: We included fifty-eight patients who have recovered from COVID-19 (group 1) and fifty healthy control subjects (group 2) in this prospective study. Best corrected visual acuity, anterior segment and posterior segment examinations of all subjects were performed. CT scan and measurements were taken with the EDI mode of the Spectral Domain OCT device. RESULTS: Of the 108 subjects included in this study, 57 were female and 51 were male. The mean age was similar in both groups (36.10 ± 7.12 and 35.58 ± 7.29, respectively, p = 0.276). Group 1 had the following characteristics: the mean time since diagnosis was 53.18 ± 2.84; it had been 38.48 ± 4.07 days since the PCR test was negative; and all subjects were outpatients. It was detected that the CT of the patients in group 1 decreased in all areas compared to group 2, and this decrease was significant in subfoveal, temporal and inferior areas (257.48 ± 32.79, 273.62 ± 45.04, p = 0.04; 232.96 ± 41.79, 252.76 ± 46.09, p = 0.02, and 245.22 ± 44.58, 271.54 ± 55.07, p = 0.01, respectively). In the retinal nerve fiber layer analysis for group 1, thickening was detected in all areas, although it was not statistically significant, except in the temporal area where it was (superotemporal, superonasal, nasal, inferonasal, inferotemporal, temporal, and global [p = 0 .08, p = 0.45, p = 0.73, p = 0.64, p = 0.74, p = 0.02, and p = 0.10, respectively]). CONCLUSION: For individuals who had recovered from COVID-19, it was found that CT decreased in all areas in these patients. Therefore, this study in which we have demonstrated the decrease in the thickness of the choroidal tissue, a tissue with high blood flow, may contribute to the understanding of the systemic microvascular waste of this disease.

Retinal and choroidal manifestations of COVID-19.

PURPOSE OF REVIEW: The novel coronavirus disease in 2019 (COVID-19) has a wide range of systemic manifestations. Ocular manifestations are now well recognized, with conjunctivitis being the most common. Posterior segment involvement is uncommon and has mainly been described in case reports. This review provides an overview of the posterior segment involvement of COVID-19. RECENT FINDINGS: Severe acute respiratory syndrome coronavirus 2 affects the retina and the choroid through either direct entry or triggering an indirect inflammatory response. Majority of the retinal findings is a result of microvascular derangement leading to cotton wool spots, intraretinal hemorrhages, paracentral acute middle maculopathy, acute macular neuroretinopathy, or retinal vein occlusions. Rarely, inflammation involving the retina or the choroid, or reactivation of previously quiescent uveitis, can be seen. SUMMARY: It is important to recognize the possible correlation between ophthalmic conditions and COVID-19 as it can aid in diagnosis, management, and mitigation of the disease.

Posterior ocular structural and vascular alterations in severe COVID-19 patients.

PURPOSE: This study aimed to evaluate posterior ocular structural and vascular changes in severe coronavirus disease 2019 (COVID-19) patients. METHODS: This was an observational, prospective, and controlled study including 106 eyes of 53 severe COVID-19 patients, compared to after recovery and 106 eyes of 53 age- and gender-matched healthy controls. All subjects were previously healthy adults and were assessed using spectral domain optical coherence tomography (SD-OCT) and ImageJ software. Subfoveal over a 1500-µm span and macular over a 6000-µm span cross-sectional areas of the vascular, stromal, and total choroid were measured. RESULTS: Of the 53 included patients, 28 (52.8%) were male, and 25 (47.2%) were female, with a mean age of 50.2 ± 7.4 years. In the active period of the disease, compared to after recovery and healthy controls, the outer plexiform layer thickness showed a significant increase (p = 0.004), and mean choroidal thickness was significantly higher (p < 0.0001); however, choroidal vascularity was significantly lower (p < 0.0001). The stromal area to vascular area (S/V) ratio of the choroid was significantly increased (p < 0.0001). All quadrants of the peripapillary retinal nerve fiber layer (RNFL) thicknesses were significantly increased (for all, p < 0.05). The reflectivity of OCT echo of the choroid and peripapillary RNFL was significantly higher (p = 0.023, p < 0.0001, respectively). CONCLUSION: This study detected significant posterior ocular structural and vascular alterations in patients with severe COVID-19 infections. These findings may be associated with direct host-virus interaction or linked to an autoimmune process, vasculopathy, or viral-mediated inflammation.