Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

Recruiting

• Conditions: COVID-19; Post-COVID-19 Syndrome
• Interventions: 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

• Registration Number: NCT05650905
• Lead Sponsor: Medical University of Vienna

Brief Summary

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

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 Timeline

• Study Start: 2021-07-26
• Status Verified: 2022-12
• Study First Submitted: 2022-12-13
• Study First Submitted QC: 2022-12-13
• Study First Posted: 2022-12-14
• Last Update Submitted: 2022-12-14
• Last Update Posted: 2022-12-16
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

Read More

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

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
subjects previously infected with COVID-19	Fourier domain optical coherence tomography (FDOCT)	subjects previously infected with COVID-19
subjects previously infected with COVID-19	Dynamic Vessel Analyzer (DVA)	subjects previously infected with COVID-19
subjects previously infected with COVID-19	Optical coherence tomography (OCT)	subjects previously infected with COVID-19
subjects previously infected with COVID-19	Proteomics and Metabolites in Plasma, tear fluid and finger sweat	subjects previously infected with COVID-19
subjects previously infected with COVID-19	Laser Speckle Flowgraphy (LSFG)	subjects previously infected with COVID-19
healthy age-and sex- matched control subjects with no history of COVID-19 infection	Optical coherence tomography (OCT)	healthy age-and sex- matched control subjects with no history of COVID-19 infection
healthy age-and sex- matched control subjects with no history of COVID-19 infection	Laser Speckle Flowgraphy (LSFG)	healthy age-and sex- matched control subjects with no history of COVID-19 infection
healthy age-and sex- matched control subjects with no history of COVID-19 infection	Proteomics and Metabolites in Plasma, tear fluid and finger sweat	healthy age-and sex- matched control subjects with no history of COVID-19 infection
subjects with long COVID-19	Laser Speckle Flowgraphy (LSFG)	subjects with long COVID-19 according to the WHO-guideline
subjects with long COVID-19	Dynamic Vessel Analyzer (DVA)	subjects with long COVID-19 according to the WHO-guideline
subjects with long COVID-19	Optical coherence tomography (OCT)	subjects with long COVID-19 according to the WHO-guideline
healthy age-and sex- matched control subjects with no history of COVID-19 infection	Dynamic Vessel Analyzer (DVA)	healthy age-and sex- matched control subjects with no history of COVID-19 infection
subjects with long COVID-19	Proteomics and Metabolites in Plasma, tear fluid and finger sweat	subjects with long COVID-19 according to the WHO-guideline
healthy age-and sex- matched control subjects with no history of COVID-19 infection	Fourier domain optical coherence tomography (FDOCT)	healthy age-and sex- matched control subjects with no history of COVID-19 infection
subjects with long COVID-19	Fourier domain optical coherence tomography (FDOCT)	subjects with long COVID-19 according to the WHO-guideline

Primary Outcome Measures

Name	Time	Method
Retinal neurovascular coupling	Day 0	Retinal neurovascular coupling will be assessed using the DVA

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Medical University of Vienna, Department of Clinical Pharmacology; 🇦🇹 Vienna, Austria