Retinal Vessel Leakage in Cerebral Small Vessel Disease

Official title

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

Overview

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).

Interventions

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

Primary outcome measures

• Retinal vessel leakage by automated segmentation [Time frame: within one angiogram]
• Retinal vessel leakage by manual grading [Time frame: within one angiogram]

Secondary outcome measures (8)

• Baseline blood-brain barrier breakdown [Time frame: Within one MRI scan]
• White matter hyperintensity (WMH) volume adjusted for brain volume [Time frame: Within one MRI scan]
• Change in white matter hyperintensity (WMH) volume adjusted for brain volume [Time frame: Difference in MRI scans up to 5 years prior]
• Fazekas score [Time frame: Within one MRI scan]
• Change in Fazekas score [Time frame: Difference in MRI scans up to 5 years prior]
• Baseline average leakage in white matter hyperintensities [Time frame: Within one MRI scan]
• Baseline average leakage in deep grey matter [Time frame: Within one MRI scan]
• Baseline number of leakage hotspots [Time frame: Within one MRI scan]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United Kingdom · 1 center

• NHS Lothian — Edinburgh

Publications

• 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 disea PMID 33817338
• 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. PMID 26403288

Identifiers

NCT: NCT06416371 · AC24000

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗