Investigating Multimodally Endothelial Dysfunction in Ocular and Systemic Disease

To explore the distribution of retinal vasculature parameters in patients with different subtypes of cardiovascular and ocular disease.

Study Overview

• Status: Recruiting
• Conditions: Kidney Diseases; Glaucoma; Diastolic Heart Failure; Small Vessel Disease
• Intervention / Treatment: Diagnostic test: Optical coherence tomography(-angiography) OCT(A); Diagnostic test: Fundus pictures; Diagnostic test: DVA 3.0; Diagnostic test: Hyperspectral retinal images; Diagnostic test: SphygmoCor; Diagnostic test: Sphygmomanometer; Diagnostic test: Blood sample; Diagnostic test: Skin biopsy; Diagnostic test: Neuropsychological examination

Detailed Description

In this interventional cohort study, the investigators aim to evaluate retinal vascular function as assessed by optical coherence tomography angiography, fundus photography and dynamic vessel analysis in patients who share microvascular involvement of their pathology (e.g. chronic kidney disease, cardiac decompensation, neuronal small vessel disease and glaucoma) and age-matched healthy controls. Plasm and skin samples for comparative proteomics and transcriptomics are also taken.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Spileers, SC; Phone Number: +32 16 34 03 91; Email: oogziekten.glaucoomstudies@uzleuven.be
• Study Contact Backup: Name: Jan Van Eijgen, MD; Phone Number: +32 16 34 56 28; Email: jan.1.vaneijgen@uzleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • Universitaire Ziekenhuizen UZ/KU Leuven
      • Contact: Sarah Spileers, SC; Phone Number: +32 16 34 03 91; Email: oogziekten.glaucoomstudies@uzleuven.be
      • Sub-Investigator: Mathieu Vandenbulcke, MD, PHD
      • Sub-Investigator: Amaryllis Van Craenenbroeck, MD, PhD
      • Sub-Investigator: Jan Van Eijgen, MD
      • Sub-Investigator: Véronique Cornelissen, MD, PHD
      • Sub-Investigator: Elisabeth Jones, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult patients with a confirmed or suspect diagnosis of glaucoma based on intra-ocular eye pressure, visual field defect and structural optic nerve changes, regardless their age.
• Adult patients with chronic kidney disease regardless their age.
• Adult patients with heart failure with preserved ejection fraction (HFpEF), regardless their age: symptomatic heart failure with Left Ventricle Ejection Fraction > 50% AND BNP > 35 pg/ml (or NT-proBNP>125 pg/ml) OR signs of diastolic dysfunction according to the European Society of Cardiology guidelines 2016
• Adult patients with confirmed small vessel disease as is diagnosed on routine neurological imaging, regardless their age.
• People without history or track record of any relevant pathology, including cardiovascular and renal diseases, regardless their age
• Capable and willing to participate (informed consent)

Exclusion Criteria:

• Diabetes
• Personal medical history of retinal neovascularization.
• Unable or unwilling to give consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Chronic kidney disease	Diagnostic test: Optical coherence tomography(-angiography) OCT(A); OCTA is a non-invasive diagnostic tool capable of generating cross-sectional coupes of the retina and choroid. Novel algorithms allow to render a 3-dimensional model of the ocular microcirculation based merely on the motion contrast of the circulating blood.; Diagnostic test: Fundus pictures; Visucam (Zeiss), Topcon NW8 fundus camera, NFC 600 (Crystalvue); Diagnostic test: DVA 3.0; IMEDOS GmbH; Diagnostic test: Hyperspectral retinal images; Ximea SNm4x4 hyperspectral snapshot camera; Diagnostic test: SphygmoCor; Sphygmocor Excell; Diagnostic test: Sphygmomanometer; For the measurement of the blood pressure.; Diagnostic test: Blood sample; For both routine cardiovascular health biomarkers as well as genetic markers (DNA, mRNA, miRNA).; Diagnostic test: Skin biopsy; Spatial proteomics and transcriptomics for endothelial function.; Diagnostic test: Neuropsychological examination; Moca, Stroop color word test, concept shifting test, COWAT, (R)AVLT, Beck depression inventory, GDS
Other: Diastolic heart failure	Diagnostic test: Optical coherence tomography(-angiography) OCT(A); OCTA is a non-invasive diagnostic tool capable of generating cross-sectional coupes of the retina and choroid. Novel algorithms allow to render a 3-dimensional model of the ocular microcirculation based merely on the motion contrast of the circulating blood.; Diagnostic test: Fundus pictures; Visucam (Zeiss), Topcon NW8 fundus camera, NFC 600 (Crystalvue); Diagnostic test: DVA 3.0; IMEDOS GmbH; Diagnostic test: Hyperspectral retinal images; Ximea SNm4x4 hyperspectral snapshot camera; Diagnostic test: SphygmoCor; Sphygmocor Excell; Diagnostic test: Sphygmomanometer; For the measurement of the blood pressure.; Diagnostic test: Blood sample; For both routine cardiovascular health biomarkers as well as genetic markers (DNA, mRNA, miRNA).; Diagnostic test: Skin biopsy; Spatial proteomics and transcriptomics for endothelial function.; Diagnostic test: Neuropsychological examination; Moca, Stroop color word test, concept shifting test, COWAT, (R)AVLT, Beck depression inventory, GDS
Other: Neuronal small vessel disease	Diagnostic test: Optical coherence tomography(-angiography) OCT(A); OCTA is a non-invasive diagnostic tool capable of generating cross-sectional coupes of the retina and choroid. Novel algorithms allow to render a 3-dimensional model of the ocular microcirculation based merely on the motion contrast of the circulating blood.; Diagnostic test: Fundus pictures; Visucam (Zeiss), Topcon NW8 fundus camera, NFC 600 (Crystalvue); Diagnostic test: DVA 3.0; IMEDOS GmbH; Diagnostic test: Hyperspectral retinal images; Ximea SNm4x4 hyperspectral snapshot camera; Diagnostic test: SphygmoCor; Sphygmocor Excell; Diagnostic test: Sphygmomanometer; For the measurement of the blood pressure.; Diagnostic test: Blood sample; For both routine cardiovascular health biomarkers as well as genetic markers (DNA, mRNA, miRNA).; Diagnostic test: Skin biopsy; Spatial proteomics and transcriptomics for endothelial function.; Diagnostic test: Neuropsychological examination; Moca, Stroop color word test, concept shifting test, COWAT, (R)AVLT, Beck depression inventory, GDS
Other: Glaucoma	Diagnostic test: Optical coherence tomography(-angiography) OCT(A); OCTA is a non-invasive diagnostic tool capable of generating cross-sectional coupes of the retina and choroid. Novel algorithms allow to render a 3-dimensional model of the ocular microcirculation based merely on the motion contrast of the circulating blood.; Diagnostic test: Fundus pictures; Visucam (Zeiss), Topcon NW8 fundus camera, NFC 600 (Crystalvue); Diagnostic test: DVA 3.0; IMEDOS GmbH; Diagnostic test: Hyperspectral retinal images; Ximea SNm4x4 hyperspectral snapshot camera; Diagnostic test: SphygmoCor; Sphygmocor Excell; Diagnostic test: Sphygmomanometer; For the measurement of the blood pressure.; Diagnostic test: Blood sample; For both routine cardiovascular health biomarkers as well as genetic markers (DNA, mRNA, miRNA).; Diagnostic test: Skin biopsy; Spatial proteomics and transcriptomics for endothelial function.; Diagnostic test: Neuropsychological examination; Moca, Stroop color word test, concept shifting test, COWAT, (R)AVLT, Beck depression inventory, GDS
Other: Healthy patients	Diagnostic test: Optical coherence tomography(-angiography) OCT(A); OCTA is a non-invasive diagnostic tool capable of generating cross-sectional coupes of the retina and choroid. Novel algorithms allow to render a 3-dimensional model of the ocular microcirculation based merely on the motion contrast of the circulating blood.; Diagnostic test: Fundus pictures; Visucam (Zeiss), Topcon NW8 fundus camera, NFC 600 (Crystalvue); Diagnostic test: DVA 3.0; IMEDOS GmbH; Diagnostic test: Hyperspectral retinal images; Ximea SNm4x4 hyperspectral snapshot camera; Diagnostic test: SphygmoCor; Sphygmocor Excell; Diagnostic test: Sphygmomanometer; For the measurement of the blood pressure.; Diagnostic test: Blood sample; For both routine cardiovascular health biomarkers as well as genetic markers (DNA, mRNA, miRNA).; Diagnostic test: Skin biopsy; Spatial proteomics and transcriptomics for endothelial function.; Diagnostic test: Neuropsychological examination; Moca, Stroop color word test, concept shifting test, COWAT, (R)AVLT, Beck depression inventory, GDS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Relative distribution of retinal endothelial reactivity, flow index, vessel density in the different subpopulations.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Diagnostic performance of the aforementioned parameters to distinguish the different subpopulations.	3 years
The association between these parameters and (1) the presence of risk factors for cardiovascular disease (including biomarkers) and (2) risk factors for disease progression and (3) neuropsychological functioning	3 years
Physiological behaviour of retinal vasculature under cardiovascular stress.	3 years
Histopathological correlates in dermal microvasculature	3 years

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Ingeborg Stalmans, MD, PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Urologic Diseases; Heart Failure; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Heart Failure, Diastolic
• Other Study ID Numbers: S63649

Drug and device information, study documents

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