Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

NCT ID: NCT05650905

Last Updated: 2025-05-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 90 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-07-26
• Study Completion Date: 2025-12-31

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.

Conditions

COVID-19; Post-COVID-19 Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

subjects previously infected with COVID-19

subjects previously infected with COVID-19

Dynamic Vessel Analyzer (DVA)

Intervention Type: DEVICE

Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA

Fourier domain optical coherence tomography (FDOCT)

Intervention Type: DEVICE

Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT

Optical coherence tomography (OCT)

Intervention Type: DEVICE

Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT

Laser Speckle Flowgraphy (LSFG)

Intervention Type: DEVICE

Normalized blur and Relative flow volume will be assessed using the LSFG

Proteomics and Metabolites in Plasma, tear fluid and finger sweat

Intervention Type: DIAGNOSTIC_TEST

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

Dynamic Vessel Analyzer (DVA)

Intervention Type: DEVICE

Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA

Fourier domain optical coherence tomography (FDOCT)

Intervention Type: DEVICE

Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT

Optical coherence tomography (OCT)

Intervention Type: DEVICE

Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT

Laser Speckle Flowgraphy (LSFG)

Intervention Type: DEVICE

Normalized blur and Relative flow volume will be assessed using the LSFG

Proteomics and Metabolites in Plasma, tear fluid and finger sweat

Intervention Type: DIAGNOSTIC_TEST

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

healthy age-and sex- matched control subjects with no history of COVID-19 infection

Dynamic Vessel Analyzer (DVA)

Intervention Type: DEVICE

Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA

Fourier domain optical coherence tomography (FDOCT)

Intervention Type: DEVICE

Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT

Optical coherence tomography (OCT)

Intervention Type: DEVICE

Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT

Laser Speckle Flowgraphy (LSFG)

Intervention Type: DEVICE

Normalized blur and Relative flow volume will be assessed using the LSFG

Proteomics and Metabolites in Plasma, tear fluid and finger sweat

Intervention Type: DIAGNOSTIC_TEST

Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test

Interventions

Dynamic Vessel Analyzer (DVA)

Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA

Intervention Type: DEVICE

Fourier domain optical coherence tomography (FDOCT)

Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT

Intervention Type: DEVICE

Optical coherence tomography (OCT)

Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT

Intervention Type: DEVICE

Laser Speckle Flowgraphy (LSFG)

Normalized blur and Relative flow volume will be assessed using the LSFG

Intervention Type: DEVICE

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Doreen Schmidl

Associate Professor, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of Vienna, Department of Clinical Pharmacology

Vienna, Vienna, Austria

Site Status: RECRUITING

Countries

Austria

Facility Contacts

Doreen Schmidl, MD, PhD

Role: primary

klin-pharmakologie@meduniwien.ac.at

0043140400 ext. 29810

References

Pai V, Bileck A, Hommer N, Janku P, Lindner T, Kauer V, Rumpf B, Haslacher H, Hagn G, Meier-Menches SM, Schmetterer L, Schmidl D, Gerner C, Garhofer G. Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients. Sci Rep. 2024 Apr 10;14(1):8395. doi: 10.1038/s41598-024-56834-4.

Reference Type: DERIVED

PMID: 38600099 (View on PubMed)

Other Identifiers

OPHT-180520

Identifier Type: -

Identifier Source: org_study_id