Estimation of Intracranial Pressure Using Non-invasive Fundus Videos

The purpose of this pilot study is to assess whether the intracranial pressure (ICP) can be detected by using a non-invasive retinal fundus scanner, recording the vessels of the eye entering from the optic disc. The artery's diameter (A) is measured and compared to the vein's diameter (V) thereby a ratio A/V can be calculated. This ratio is compared to the values obtained from conventional fiberoptic intraparenchymal, intraventricular ICP monitoring using external ventricular drain (EVD) or lumbar pressure monitoring.

Valid non-invasive techniques for objective measurements of the intracranial pressure do not exist at the given time now and this study could prove to help the development of monitoring patients ICP without surgical intervention.

Study Overview

• Status: Recruiting
• Conditions: Intracranial Pressure
• Intervention / Treatment: Diagnostic test: Fundus videos

Detailed Description

Intracranial pressure (ICP) is based on the simple principle of Monroe-Kellie Doctrine. Since the volume of the cranial cavity is constant and the brain, CSF and blood can only compensate for a certain change in volume, pressure will increase at a critical increase in volume. An increase in pressure caused by an increase in intracranial volume is distributed throughout the entire brain and spinal canal equally. The normal range of ICP varies with age. Normal values are less than 10-15 mmHg for adults and adolescents, 3-7 mmHg for younger children and 1.5-6 mmHg for newborns even sub-atmospheric ICP has been shown.

The threshold for intracranial hypertension varies in the literature, which is reflected in the clinical use. Generally, ICP above 20 mmHg is defined intracranial hypertension. ICP higher than 20-25 may require treatment, and continuous ICP above 40 mmHg indicates severe, lethal intracranial hypertension.

Some forms of measurements, e.g. 1. Intraparenchymal strain gauge or fiber optics or 2. Intraventricular ICP monitoring via external ventricular drain (EVD). EVD is considered golden standard, but in the daily clinic there is often no or limited difference between 1. and 2. The issue regarding invasive methods are the same as for any surgical procedure, e.g. bleeding and infection. Risk of bleeding is 2-10% for EVD and 2.5% for intraparenchymal monitors. The consequences of such a bleed can be severe and result in disability. EVD has a higher risk of infection (5-20%) compared to intraparenchymal monitors (0-0.1%).

Non-invasive methods such as transcranial doppler ultrasound pulsation index and optic nerve sheath diameter has been used in studies, which seemed promising, but has not yet been validated for routine clinical use. Also, in non-invasive methods there are significant inter observational variation.

Studies of the eye's fundus have shown a correlation between ICP and ratio between artery and vein diameter (A/V ratio, unpublished data) Currently, there are no published work that has considered the correlation between A/V ratio and ICP, however there is a study with a theoretical prediction of such a correlation (Babbs CF 2016. Weldon School of Biomedical Engineering Faculty Working Papers. Paper 1 http://docs.lib.purdue.edu/bmewp/1).

This study investigates the correlation between non-invasive fundus ICP estimation and intracranial pressure monitoring.

In practice, all conscious and able adults admitted to Odense University Hospital for intracranial pressure monitoring/measurements by either an EVD, intraparenchymal ICP monitor or lumbar spinal fluid pressure assessment are enrolled.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Denmark
  • Danmark
    • Odense C, Danmark, Denmark, 5000
      • Recruiting
      • Department of Neurosurgery, Odense University Hospital
      • Contact: Frantz R Poulsen, MD, PhD; Phone Number: 0045 65411835; Email: frantz.r.poulsen@rsyd.dk
      • Contact: Mikkel S Andersen, MD; Phone Number: 0045 25618181; Email: mikkel.c.schou.andersen@rsyd.dk
      • Sub-Investigator: Mikkel S Andersen, MD
      • Principal Investigator: Frantz R Poulsen, MD, PhD
      • Sub-Investigator: Christian B Pedersen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All conscious and able patients of 18 years and older admitted for intracranial pressure monitoring in the department of neurosurgery (Camino, Integra, Switzerland)

Description

Inclusion Criteria:

• Adults 18 years or older with indication for intraparenchymal or intraventricular ICP monitoring
• Conscious and able
• Admission to the Department of Neurosurgery or Department of Neurology at Odense University Hospital

Exclusion Criteria:

• Disabled and unconscious
• No intraparenchymal or intraventricular ICP monitoring

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ventriculoperitoneal dysfunction; Patients with suspected ventriculo-peritoneal (VP) shunt dysfunction are admitted to the neurosurgical department for intracranial pressure monitoring for 24 hours. The patients are approached within this time frame.	Diagnostic test: Fundus videos; Recordings of fundus videos
Normal Pressure Hydrocephalus (NPH); Patients with suspected NPH (triad of cognitive dysfunction, urine incontinence of urge type, abnormal gait) are admitted to the neurosurgical department for intracranial pressure monitoring for 24 hours. The following day an infusiontest is performed, where data is collected.	Diagnostic test: Fundus videos; Recordings of fundus videos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute A/V ratio value to conventional intracranial pressure monitors	Comparison of A/V ratio values from the fundus video analysis and conventional intraparenchymal intracranial pressure (ICP), intraventricular ICP monitoring or lumbar pressure monitoring.	2025

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in A/V ratio value compared to increased intracranial pressure monitor during infusion test.	Assessment of the use of the fundus videos in patients undergoing a lumbar infusion test for 20 minutes for assessment of normal intracranial pressure compared to a conventional intraparenchymal ICP monitor.	2025

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Statumanu Icp ApS

Publications and helpful links

General Publications

• Andersen MS, Pedersen CB, Poulsen FR. A new novel method for assessing intracranial pressure using non-invasive fundus images: a pilot study. Sci Rep. 2020 Aug 3;10(1):13062. doi: 10.1038/s41598-020-70084-0.

Helpful Links

• Biomechanics of Retinal Venous Pulsations as Indicators of Intracranial Pressure

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: December 19, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Intracranial pressure monitoring; Intracranial Hypertension; Normal pressure hydrocephalus; Non-invasive point-of-care device
• Other Study ID Numbers: S-20170038; 2012-58-0018 (Other Identifier: Datatilsynet, Region of Southern Denmark)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We wish to share all data of individual intracranial pressure values and A/V ratio.

Drug and device information, study documents

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