Retinal Vessel Leakage in Cerebral Small Vessel Disease

Recruiting

• Conditions: Cerebral Small Vessel Diseases; Vascular Dementia; Lacunar Stroke

• Registration Number: NCT06416371
• Lead Sponsor: University of Edinburgh

Brief Summary

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.

Detailed Description

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:

1. Test the feasibility of fluorescein angiography in people with SVD

2. Discover if retinal vessel leakage occurs people with SVD

3. 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).

Study Timeline

• Study First Submitted: 2024-01-15
• Study First Submitted QC: 2024-05-14
• Study First Posted: 2024-05-16
• Study Start: 2025-01-13
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-14
• Primary Completion: 2025-05
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Retinal vessel leakage by automated segmentation	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.
Retinal vessel leakage by manual grading	within one angiogram	The presence and severity of retinal vessel leakage will be measured using an manual ordinal grading scale

Secondary Outcome Measures

Name	Time	Method
Baseline blood-brain barrier breakdown	Within one MRI scan	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
Change in white matter hyperintensity (WMH) volume adjusted for brain volume	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
Baseline number of leakage hotspots	Within one MRI scan	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
Fazekas score	Within one MRI scan	This is measured from the most recent structural MRI scan
Baseline average leakage in deep grey matter	Within one MRI scan	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium
White matter hyperintensity (WMH) volume adjusted for brain volume	Within one MRI scan	This is measured from the most recent structural MRI scan
Change in Fazekas score	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
Baseline average leakage in white matter hyperintensities	Within one MRI scan	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium

Trial Locations

Locations (1)

NHS Lothian; 🇬🇧 Edinburgh, United Kingdom