Retinal Microcirculation as a Correlate of a Systemic Capillary Impairment After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), affects the pulmonary systems via angiotensin-converting enzyme-2 (ACE-2) receptor, being an entry to systemic infection. As COVID-19 disease features ACE-2 deficiency, a link to microcirculation is proposed. Optical coherence tomography angiography (OCT-A) enables non-invasive analysis of retinal microvasculature. Thus, an impaired systemic microcirculation might be mapped on retinal capillary system. As recent OCT-A studies, analyzing microcirculation in two subdivided layers, yielded contrary results, an increased subdivision of retinal microvasculature might offer an even more fine analysis. The aim of the study was to investigate retinal microcirculation by OCT-A after COVID-19 infection in three subdivided layers (I). In addition, short-term retinal affections were monitored during COVID-19 disease (II). Considering (I), a prospective study (33 patientspost−COVID and 28 controls) was done. Macula and peripapillary vessel density (VD) were scanned with the Spectralis II. Macula VD was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Analysis was done by the EA-Tool, including an Anatomical Positioning System and an analysis of peripapillary VD by implementing Bruch's membrane opening (BMO) landmarks. Overall, circular (c1, c2, and c3) and sectorial VD (s1-s12) was analyzed. Considering (II), in a retrospective study, 29 patients with severe complications of COVID-19 infection, hospitalized at the intensive care unit, were monitored for retinal findings at bedside during hospitalization. (I) Overall (p = 0.0133) and circular (c1, p = 0.00257; c2, p = 0.0067; and c3, p = 0.0345). VD of the ICP was significantly reduced between patientspost−COVID and controls, respectively. Overall (p = 0.0179) and circular (c1, p = 0.0189) peripapillary VD was significantly reduced between both groups. Subgroup analysis of hospitalized vs. non-hospitalized patientspost−COVID yielded a significantly reduced VD of adjacent layers (DCP and SVP) with increased severity of COVID-19 disease. Clinical severity parameters showed a negative correlation with VD (ICP) and peripapillary VD. (II) Funduscopy yielded retinal hemorrhages and cotton wool spots in 17% of patients during SARS-CoV-2 infection. As VD of the ICP and peripapillary regions was significantly reduced after COVID-19 disease and showed a link to clinical severity markers, we assume that the severity of capillary impairment after COVID-19 infection is mapped on retinal microcirculation, visualized by non-invasive OCT-A.

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“…Those microvascular OCT-A scans correlate well with the human anatomy ( 21 ). A previous study showed that especially in the intermediate capillary plexus (ICP) and peripapillary region, a significantly decreased vessel density (VD) was observed after COVID-19 compared to healthy eyes ( 36 ). In cases of severe COVID-19 during acute infection, the adjacent retinal microvascular layers were impaired as well (SVP, DCP).…”

“…Especially, AAbs targeting G-protein coupled receptors (GPCR-AAbs) were observed in the sera of patients recovered from acute COVID-19, with an apparent link to blood microcirculation ( 8 ). Recent studies by noninvasive optical coherence tomography angiography (OCT-A) suggested that even months after COVID-19, ocular capillary microcirculation is impaired ( 9 , 36 ). We propose that the capillary impairment might be induced in part by the agonistic GPCR-AAb targeting ß2-adrenergic receptor (ß2-AR).…”

Retinal vessels modifications in acute and post-COVID-19

“…This suggests that haemorrhages and cotton wools, which have commonly been reported in COVID-19 6 , 28 , along with other thrombotic events to the retinal vasculature 7 , 8 , are likely related to an impairment to the retinal microcirculation 28 induced by the transient hypercoagulability 20 and the endothelial disfunction 29 typical of the acute phase of the disease. Such damage to the microcirculation may persist at a subclinical level according to optical coherence tomography studies which demonstrated a decreased vascular density in the macular 10 and peripapillary area 12 of post-COVID-19 patients.…”

“…The eyes can be affected at many levels by SARS-CoV-2 as the virus has been isolated in the tears 3 , the conjunctiva 4 and even the retina 5 . Although no disease-specific lesions have been described neither in the anterior nor in the posterior segment of the eye many authors have reported the occurrence of direct or indirect signs of retinal circulation alterations in patients with COVID-19 ranging from retinal haemorrhages and cotton wool spots 6 , retinal vein occlusions 7 , 8 to a significant reduction in vascular density measured by optical coherence tomography angiography 9 – 12 .…”

Case Report: Recanalization of Branch Retinal Artery Occlusion Due to Microthrombi Following the First Dose of SARS-CoV-2 mRNA Vaccination

“…Its clinical features are reversible, except in ischemic central RVO ( Bialasiewicz et al, 2021 ; Endo et al, 2021 ). The vascular density of the peri-papillary region was significantly decreased on OCT angiography in patients with COVID-19 and associated with clinical severity markers ( Hohberger et al, 2021 ). If thrombosis develops in the central retinal artery, ophthalmologists, and vaccinated individuals should remain vigilant because of irreversible visual deterioration, particularly since the incidence of spontaneous recanalization from occlusion is as low as approximately 15% ( Ahn et al, 2015 ).…”