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NCT Number: NCT06416371

Retinal Vessel Leakage in Cerebral Small Vessel Disease

The goal of this observational study is to learn about leakage from retinal vessels in cerebral small vessel disease. The main questions it aims to answer are:

* Does retinal vessel leakage occur in cerebral small vessel disease? * If it does, is the severity of retinal vessel leakage similar to the severity of cerebral small vessel disease generally?

Participants will be tested using fluorescein angiography. This involves an intravenous injection of fluorescent dye, and is a very sensitive way to find leakage from retinal blood vessels.

Participants will have already had brain scans and other examinations and tests to measure the severity of their cerebral small vessel disease. Our new retinal images will complement the information from these previous tests.

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Key information

About this study

Cerebral small vessel disease (SVD) is a common cause of stroke and dementia. The molecular causes are unclear, limiting new therapies. Breakdown of the blood-brain barrier (BBB) is characteristic and may damage brain tissue. However, specialist MRI scans to measure BBB breakdown are expensive and time-consuming.

In contrast, measuring leakage from retinal blood vessels is relatively simple. The blood-retina barrier is very similar to the BBB, and SVD is likely to damage retinal and brain blood vessels in the same way. If so, then retinal angiography could be used to study SVD pathogenesis and measure the effect of new treatments with much greater resolution and lower cost than MRI.

We have three aims:

  • Test the feasibility of fluorescein angiography in people with SVD
  • Discover if retinal vessel leakage occurs people with SVD
  • Discover whether the severity of retinal vessel leakage is associated with clinical features of SVD

We will recruit participants from a well-established cohort of people with SVD - the Mild Stroke Study 3 (MSS3).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Membership in the Mild Stroke Study 3 cohort
  • Contrast enhanced MRI within 12 months
  • Clear optical media in both eyes, as assessed by study investigator
  • Best corrected visual acuity (near vision) ≥N36

Exclusion criteria

  • Any condition known to cause retinal leakage (i.e., worse than background diabetic retinopathy, retinal vein occlusion, active uveitis, wet age-related macular degeneration, malignant hypertension)
  • Previous treatment for retinal leakage (retinal laser, intravitreal anti-VEGF)
  • Recent eye surgery
  • Shallow anterior chambers as assessed by torch test
  • Pregnancy, renal failure
  • Severe dementia
  • Known allergy to fluorescein
  • History of allergy such as food or drug induced urticaria or history of bronchial asthma
  • Any other severe or acute medical or psychiatric conditions
  • Inability to give informed consent

Treatment and study plan

Fundus fluorescein angiography, with ultrawide field retinal imaging

Diagnostic Test

Intravenous injection of sodium fluorescein for angiography of retinal blood vessels

Primary outcomes

  1. Retinal vessel leakage by automated segmentation

    Time frame: within one angiogram

    The presence and severity of retinal vessel leakage will be measured for each eye in terms of change in pixel brightness over the duration of the angiogram.

  2. Retinal vessel leakage by manual grading

    Time frame: within one angiogram

    The presence and severity of retinal vessel leakage will be measured using an manual ordinal grading scale

Secondary outcomes

  1. Baseline blood-brain barrier breakdown

    Time frame: Within one MRI scan

    BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium

  2. White matter hyperintensity (WMH) volume adjusted for brain volume

    Time frame: Within one MRI scan

    This is measured from the most recent structural MRI scan

  3. Change in white matter hyperintensity (WMH) volume adjusted for brain volume

    Time frame: Difference in MRI scans up to 5 years prior

    This is measured by comparing the most recent structural MRI scan with the baseline structural MRI scan

  4. Fazekas score

    Time frame: Within one MRI scan

    This is measured from the most recent structural MRI scan

  5. Change in Fazekas score

    Time frame: Difference in MRI scans up to 5 years prior

    This is measured by comparing the most recent structural MRI scan with the baseline structural MRI scan

  6. Baseline average leakage in white matter hyperintensities

    Time frame: Within one MRI scan

    BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium

  7. Baseline average leakage in deep grey matter

    Time frame: Within one MRI scan

    BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium

  8. Baseline number of leakage hotspots

    Time frame: Within one MRI scan

    BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium

Sponsors and collaborators

Lead sponsor

University of Edinburgh

Other

Registry information

Official study title

Retinal Vessel Leakage in Cerebral Small Vessel Disease: a Sub-study of the Mild Stroke Study 3

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
May 16, 2024
Registry last updated
Mar 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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