Retinal Vessel Leakage in Cerebral Small Vessel Disease

Vascular Dementia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06416371
• Other study ID #: AC24000
• Status: Not yet recruiting
• Start date: September 2024
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: July 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Small Vessel Diseases
• Dementia, Vascular
• Lacunar Stroke
• Stroke, Lacunar
• Vascular Dementia

Intervention

Diagnostic Test:
• Fundus fluorescein angiography, with ultrawide field retinal imaging
Intravenous injection of sodium fluorescein for angiography of retinal blood vessels

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Edinburgh

References & Publications (2)

Clancy U, Garcia DJ, Stringer MS, Thrippleton MJ, Valdes-Hernandez MC, Wiseman S, Hamilton OK, Chappell FM, Brown R, Blair GW, Hewins W, Sleight E, Ballerini L, Bastin ME, Maniega SM, MacGillivray T, Hetherington K, Hamid C, Arteaga C, Morgan AG, Manning C, Backhouse E, Hamilton I, Job D, Marshall I, Doubal FN, Wardlaw JM. Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3. Eur Stroke J. 2021 Mar;6(1):81-88. doi: 10.1177/2396987320929617. Epub 2020 Jun 5. — View Citation

MacCormick IJ, Maude RJ, Beare NA, Borooah S, Glover S, Parry D, Leach S, Molyneux ME, Dhillon B, Lewallen S, Harding SP. Grading fluorescein angiograms in malarial retinopathy. Malar J. 2015 Sep 24;14:367. doi: 10.1186/s12936-015-0897-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Retinal vessel leakage by automated segmentation	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.	within one angiogram
Primary	Retinal vessel leakage by manual grading	The presence and severity of retinal vessel leakage will be measured using an manual ordinal grading scale	within one angiogram
Secondary	Baseline blood-brain barrier breakdown	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium	Within one MRI scan
Secondary	White matter hyperintensity (WMH) volume adjusted for brain volume	This is measured from the most recent structural MRI scan	Within one MRI scan
Secondary	Change in white matter hyperintensity (WMH) volume adjusted for brain volume	This is measured by comparing the most recent structural MRI scan with the baseline structural MRI scan	Difference in MRI scans up to 5 years prior
Secondary	Fazekas score	This is measured from the most recent structural MRI scan	Within one MRI scan
Secondary	Change in Fazekas score	This is measured by comparing the most recent structural MRI scan with the baseline structural MRI scan	Difference in MRI scans up to 5 years prior
Secondary	Baseline average leakage in white matter hyperintensities	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium	Within one MRI scan
Secondary	Baseline average leakage in deep grey matter	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium	Within one MRI scan
Secondary	Baseline number of leakage hotspots	BBB breakdown is measured by MRI in terms of image enhancement after intravenous gadolinium	Within one MRI scan