Evaluation of Retinal and Choroidal Microvasculature in SARS-CoV-2 Infection: A Review Based on Optical Coherence Tomography Angiography


The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is extensive, ranging from asymptomatic or mild cases to severe pneumonia and acute respiratory distress syndrome.

In addition, post-COVID-19 syndrome can lead to persistent symptoms affecting sensory, neurologic, cardiorespiratory, and mental health.

While ocular complications have been reported, including conjunctivitis and retinovascular disease, the impact of SARS-CoV-2 on retinal and choroidal microvasculature remains unclear. This review aims to assess the effect of SARS-CoV-2 infection on ocular vasculature using optical coherence tomography angiography (OCTA).

Retinal ischemia refers to the inadequate blood supply to the retina, which can lead to significant vision impairment and other ocular complications. In the context of COVID-19, emerging evidence suggests that retinal ischemia can be associated with the viral infection. Understanding the mechanisms and manifestations of retinal ischemia in COVID-19 patients is crucial for early detection, management, and potential interventions. This article provides an in-depth analysis of retinal ischemia, its relationship with COVID-19, and the impact on ocular health.

Anatomy and Blood Supply of the Retina: The retina, consisting of several layers, receives its blood supply primarily from the central retinal artery. The outer layers of the retina, including the retinal pigment epithelium and parts of the optic nerve, rely on the choroid for oxygenation. The vascular endothelium plays a vital role in maintaining the retinal vasculature, regulating vascular tone, and preserving the blood-retinal barrier. Disruption of these mechanisms, such as vasospasm or inflammation, can result in vascular endothelial dysfunction and subsequent retinal ischemia.

Presence of SARS-CoV-2 in the Retina: Studies have detected SARS-CoV-2 viral particles in retinal biopsies of deceased COVID-19 patients who had severe respiratory symptoms. Viral particles were observed in the perinuclear region of cells and capillary endothelial cells within the inner and outer nuclear layers of the retina. Immunofluorescence microscopy confirmed the presence of viral spike protein and nucleocapsid protein in the retina. Additionally, SARS-CoV-2 RNA has been detected in tears and conjunctival secretions, indicating potential ocular tropism of the virus.

Retinal and Choroidal Abnormalities in COVID-19: COVID-19 patients have exhibited various retinal and choroidal abnormalities during ophthalmological examinations. These include cotton wool spots, microhemorrhages, flame-shaped hemorrhages, tortuosity of retinal vessels, and dilated veins. Some patients have also shown changes in retinal ganglion cell layer and inner plexiform layer on optical coherence tomography (OCT) scans. These findings suggest that retinal ischemia and direct viral tissue injury may contribute to these ocular manifestations.

Retinal Vein and Artery Occlusions: COVID-19 patients without typical systemic vascular risk factors have been reported to experience central retinal vein and artery occlusions. The complement-induced prothrombotic and inflammatory state induced by the virus is believed to cause endothelial damage and microangiopathic injury, leading to these vascular occlusions. Monitoring retinal vein diameter has been proposed as a non-invasive parameter to assess the inflammatory response and endothelial injury caused by SARS-CoV-2 infection.

Hypoxia and Retinal Vascularization: Hypoxia plays a significant role in retinal vascularization. Studies have shown that retinal circulation can adjust blood flow in response to hypoxia and hyperoxia. Hypoxia-induced changes in retinal vessel diameter and perfusion density have been observed. The exact mechanisms behind these adaptations are still being studied, but they contribute to maintaining appropriate oxygen supply to the retina while avoiding excessive oxygen delivery that can be harmful.

Numerous studies have reported reduced vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of COVID-19 patients compared to healthy controls. However, there are discrepancies in the statistical significance of these findings, which may be attributed to variations in study groups, timing of eye examinations, disease severity, and comorbidities.

One possible mechanism for the reduced vessel density is the direct viral invasion of the retinal endothelial cells, leading to endothelial dysfunction and subsequent vascular abnormalities. SARS-CoV-2 viral particles have been detected in retinal biopsies, suggesting the potential for viral replication and tissue damage within the retinal vasculature.

Another contributing factor could be the systemic inflammatory response triggered by COVID-19. The virus induces a pro-inflammatory state in the body, leading to increased levels of cytokines and chemokines. These inflammatory mediators can disrupt the delicate balance of vascular homeostasis in the retina, resulting in vasoconstriction, endothelial cell injury, and impaired microcirculation.

Hypoxia is also implicated in the reduced vessel density observed in COVID-19 patients. The virus can cause respiratory distress and compromise lung function, leading to inadequate oxygen supply to various organs, including the retina. Hypoxia-induced adaptive changes in retinal blood flow and vessel diameter may contribute to the observed alterations in vessel density.

The implications of reduced vessel density in COVID-19 patients are significant. The retinal vasculature plays a crucial role in delivering oxygen and nutrients to the retinal tissue, maintaining its normal function. Reduced vessel density can lead to retinal ischemia, characterized by inadequate blood supply to the retina, which can result in vision loss and other ocular complications.

Early detection and monitoring of retinal vascular changes are essential in COVID-19 patients. Ophthalmological examinations, including optical coherence tomography angiography (OCTA), can provide detailed imaging of the retinal vasculature and assess vessel density. Regular follow-up examinations can help evaluate the progression of retinal vascular abnormalities and guide appropriate interventions to preserve visual function.

A literature search was conducted, focusing on original research articles and case reports published between January 2020 and March 2022. Parameters such as vessel density (VD), foveal avascular zone (FAZ), and changes over time were analyzed. The review also explores the potential gender differences in ocular vascular alterations associated with SARS-CoV-2 infection.

Introduction: The clinical manifestations of SARS-CoV-2 infection are diverse, ranging from mild to severe respiratory symptoms. However, emerging evidence suggests that the virus can affect various organ systems, including the eyes. Ophthalmic complications associated with SARS-CoV-2 have been reported, but the underlying mechanisms and effects on retinal and choroidal microvasculature are not well understood. This review aims to provide a comprehensive analysis of the impact of SARS-CoV-2 infection on ocular vasculature using OCTA.

Methods: A systematic literature search was conducted using the PubMed/Medline database to identify relevant articles published in English-language peer-reviewed journals. The search strategy included keywords related to vessel density, retinal and choroidal microvasculature, and optical coherence tomography angiography. The selected articles were limited to those published between January 2020 and March 2022 and focused on changes in retinal and choroidal microvasculature in individuals with SARS-CoV-2 infection.

Results: The review identified several studies that investigated the effect of SARS-CoV-2 infection on retinal and choroidal microvasculature using OCTA. Vessel density, which provides information about the density of blood vessels in the retina and choroid, was found to be altered in COVID-19 patients. Changes in the foveal avascular zone, a key parameter in assessing retinal perfusion, were also observed. Additionally, studies reported longitudinal changes in OCTA parameters over time, suggesting ongoing vascular alterations in convalescent COVID-19 patients. Furthermore, gender-specific differences in ocular vascular changes associated with SARS-CoV-2 infection were explored.

Conclusion: The available evidence suggests that SARS-CoV-2 infection can have an impact on retinal and choroidal microvasculature. Optical coherence tomography angiography provides valuable insights into these vascular alterations, including changes in vessel density, foveal avascular zone, and longitudinal variations. Further research is needed to elucidate the underlying mechanisms and clinical implications of these findings. Understanding the ocular manifestations of SARS-CoV-2 infection can contribute to the comprehensive management of COVID-19 patients, particularly those with ocular involvement.

reference link :https://www.mdpi.com/2075-4426/13/6/926


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