Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

The Study objective is to measure retinal neurovascular coupling and blood flow parameters in patients previously infected with COVID-19, long COVID-19 and healthy age- and sex- matched control subjects

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Post-COVID-19 Syndrome
• Intervention / Treatment: Device: Dynamic Vessel Analyzer (DVA); Device: Fourier domain optical coherence tomography (FDOCT); Device: Optical coherence tomography (OCT); Device: Laser Speckle Flowgraphy (LSFG); Diagnostic test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat

Detailed Description

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting almost all countries in the world and because of its worldwide spread has been declared as pandemic in March 2020. While respiratory symptoms are the main manifestation of acute infection, there is also increasing evidence that neurological and vascular symptoms occur, and it is unknown whether residuals remain after patients have recovered. A recent report shows that changes in the human retina are even present one month after onset of symptoms. The eye, as an extension of the brain, offers the advantage that blood vessels as well as neural tissue can be visualized non-invasively in-vivo. Neurovascular coupling is the ability of neural tissue to adapt its blood flow to its metabolic demands, a phenomenon that does not only occur in the brain, but also in the retina. In the retina, neurovascular coupling can be studied by stimulating the retina with flicker light and measuring the response of the vessels. Retinal neurovascular coupling has been found to be impaired in diseases of the central nervous system (CNS) as well as in diseases associated with endothelial dysfunction. Since COVID-19 comes with CNS manifestations as well as endothelial dysfunction, we speculate that retinal neurovascular coupling might be impaired in patients even after they have recovered from COVID-19 infection. In the current study, retinal neurovascular coupling will be measured in patients who have recovered from COVID-19 infection with and without long COVID-19 and in healthy age- and sex-matched controls with no history of COVID-19 infection. In addition, retinal oxygen saturation, vessel diameters, vessel density as well as retinal and optic nerve head blood flow will be measured. To assess structural changes, measurement of central retinal thickness as well as retinal nerve fiber layer thickness will be performed.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna, Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

A total of 90 subjects will be included:

30 subjects previously infected with COVID-19 30 subjects with long COVID-19 30 age-and sex- matched subjects with no history of COVID-19 infection

Description

Inclusion Criteria:

Inclusion criteria for healthy subjects

• Men and women aged over 18 years
• Non-smokers
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• No previous history of COVID-19 infection
• Negative testing for SARS-CoV-2 seroprevalence using nucleocapsid antibody tests
• Negative PCR test for SARS-CoV-2
• Normal ophthalmic findings, ametropy < 6 Dpt.

Inclusion criteria for subjects with history of COVID-19 infection

• Men and women aged over 18 years
• Non-smokers
• History of COVID-19 infection (confirmed by a positive PCR test for SARS-CoV2 in the medical history) within the last 6 months
• Positive testing for SARS-CoV-2 seroprevalence using spike protein IgG antibody tests
• Negative PCR test for SARS-CoV-2

Inclusion criteria for subjects with long COVID-19

• Men and women aged over 18 years
• Non-smokers
• History of COVID-19 infection (confirmed by a positive PCR test for SARS-CoV2 in the medical history)
• Positive testing for SARS-CoV-2 seroprevalence
• Negative PCR test for SARS-CoV-2
• Long Covid according to the latest WHO-Guidelines

Exclusion Criteria:

Any of the following will exclude a healthy control subject from the study:

• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• Presence or history of a severe medical condition as judged by the clinical investigator
• Participation in a clinical trial in the 3 weeks preceding the study
• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Pregnancy, planned pregnancy or lactatin
• History of epilepsia

Any of the following will exclude a subject with history of COVID-19 infection from the study:

• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Ametropy >6 Dpt
• Pregnancy, planned pregnancy or lactating
• History of epilepsia

Any of the following will exclude a subject with long COVID-19 from the study:

• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Ametropy >6 Dpt
• Pregnancy, planned pregnancy or lactating
• History of epilepsia
• Diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
subjects previously infected with COVID-19	Device: Dynamic Vessel Analyzer (DVA); Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA; Device: Fourier domain optical coherence tomography (FDOCT); Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT; Device: Optical coherence tomography (OCT); Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT; Device: Laser Speckle Flowgraphy (LSFG); Normalized blur and Relative flow volume will be assessed using the LSFG; Diagnostic test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat; Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test
subjects with long COVID-19; subjects with long COVID-19 according to the WHO-guideline	Device: Dynamic Vessel Analyzer (DVA); Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA; Device: Fourier domain optical coherence tomography (FDOCT); Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT; Device: Optical coherence tomography (OCT); Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT; Device: Laser Speckle Flowgraphy (LSFG); Normalized blur and Relative flow volume will be assessed using the LSFG; Diagnostic test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat; Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test
healthy age-and sex- matched control subjects with no history of COVID-19 infection	Device: Dynamic Vessel Analyzer (DVA); Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA; Device: Fourier domain optical coherence tomography (FDOCT); Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT; Device: Optical coherence tomography (OCT); Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT; Device: Laser Speckle Flowgraphy (LSFG); Normalized blur and Relative flow volume will be assessed using the LSFG; Diagnostic test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat; Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal neurovascular coupling	Retinal neurovascular coupling will be assessed using the DVA	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal vessel diameters	Retinal vessel diameters will be assessed using the DVA	Day 0
Retinal oxygen saturation	Retinal oxygen saturation will be assessed using the DVA	Day 0
Retinal blood velocities	Retinal blood velocities will be assessed using FDOCT	Day 0
Retinal blood flow	Retinal blood flow will be assessed using FDOCT	Day 0
Ocular perfusion pressure	Ocular perfusion pressure is going to be calulated	Day 0
Retinal nerve fiber layer thickness	Retinal nerve fiber layer thickness will be assessed using OCT	Day 0
Central retinal thickness	Central retinal thickness will be assessed using OCT	Day 0
Retinal vessel density	Retinal vessel density will be assessed using OCT	Day 0
Normalized blur	Normalized blur will be assessed using LSFG	Day 0
Relative flow volume	Relative flow volume will be assessed using LSFG	Day 0
Proteomics and Metabolites in Plasma	Proteomics and Metabolites in Plasma will be assessed through a Blood Sample	Day -14 to -1
Proteomics and Metabolites in tear fluid	Proteomics and Metabolites in tear fluid will be assessed using Schirmer	Day 0
Proteomics and Metabolites in finger sweat	Proteomics and Metabolites in finger sweat will be assessed using finger sweat filters	Day 0

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 13, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: OPHT-180520

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No