Prospective Study Phase: Retinal Oxygen Saturation, Blood Flow, Vascular Function and High Resolution Morphometric Imaging in the Living Human Eye

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Toronto
Sponsor:
Collaborator:
Ontario Research Fund
Information provided by (Responsible Party):
Chris Hudson, University of Toronto
ClinicalTrials.gov Identifier:
NCT01348672
First received: February 27, 2011
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

Canadians fear loss of vision more than any other disability. Vision loss has an enormous impact on quality-of-life and is extremely costly from a societal and economic perspective. In 2001, more than 600,000 Canadians were estimated to have severe vision loss, accounting for 17% of total disability in Canada. One in 9 individuals experience severe vision loss by 65 years of age; however, this increases to 1 in 4 individuals by 75 years. The financial cost of vision loss in Canada is $15.8 billion per year. There is a general perception that vision loss is "normal with aging" but 75% of vision loss is estimated to be preventable. The major causes of severe vision loss are age-related macular degeneration (ARMD), glaucoma, particularly primary open-angle glaucoma (POAG), and diabetic retinopathy (DR). Canada is headed for an epidemic of age-related eye disease and, unless something is done to prepare for this, severe vision loss will have significant consequences in terms of societal and economic costs. Through this proposed Research Program, and in conjunction with the investigators international academic and private sector partners, the investigators will build and develop unique quantitative imaging technologies to permit non-invasive assessment of visual changes, structural changes in the thickness of the retina at the back of the eye and also changes in the amount of blood flowing through the blood vessels that feed the retina with oxygen. This research will add to the investigators basic knowledge in predicting the development of sight-threatening change in patients with the three diseases, and facilitate earlier detection of the problem to help us discover earlier treatments for people with these conditions. The reliability of each imaging technology will be assessed by determining its ability to differentiate between diseased and healthy eyes. Cross-sectional analyses at yearly intervals, as well as change over time analyses, will be undertaken.


Condition
Age Related Macular Degeneration
Glaucoma
Diabetic Retinopathy.

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Study Phase: Retinal Oxygen Saturation, Blood Flow, Vascular Function and High Resolution Morphometric Imaging in the Living Human Eye

Resource links provided by NLM:


Further study details as provided by University of Toronto:

Primary Outcome Measures:
  • Cross-sectional relationship between retinal / ON oxygen saturation, vascular dysregulation and retinal morphometry [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To investigate the cross-sectional relationship between retinal / ON oxygen saturation, vascular dysregulation and retinal morphometry in groups of patients at risk of progres

  • Prospective relationship between retinal/ON oxygen saturation disturbances, vascular dysregulation, retinal morphometry and clinical outcomes [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To establish the prospective relationship between retinal/ON oxygen saturation disturbances, vascular dysregulation, retinal morphometry and clinical outcomes in patients at risk of progression of ARMD, POAG and DR and age-matched healthy controls

  • Topographic distribution of retinal / ON oxygen saturation disturbance, vascular dysfunction and change in morphometric parameters [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To investigate the topographic distribution of retinal / ON oxygen saturation disturbance, vascular dysfunction and change in morphometric parameters in groups of patients at risk of progression of ARMD, POAG and DR


Estimated Enrollment: 381
Study Start Date: March 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
1. ARMD Study arm

The ARMD study arm (n=150) consists of 3 groups. The groups are organised according to established risk criteria for clinical progression (AREDS, 2003).

Group 1A (n=50); Early stage ARMD with low risk of progression; several small drusen, or a few medium-sized drusen, in one or both eyes. One eye will be randomly selected for the study.

Group 2A (n=50); Intermediate ARMD with high risk of progression to advanced ARMD; many medium-sized drusen, or one or more large drusen, in one or both eyes. More severely affected eyewill be selected for the study.

Group 3A (n=50); In one eye only, either a break-down of light-sensitive cells and supporting tissue in the central retinal area (i.e. geographic atrophy), or abnormal and fragile blood vessels under the retina (i.e. choroidal neovascular membrane formation). The fellow eye is at high risk of progression to advanced ARMD. The fellow eye will be selected for the study.

2. POAG study arm

Patient groups are organised according to established risk criteria for clinical progression (EMGT, 2003).

Group 1P (n=36); Stable, early to moderate, treated patients with POAG. Early to moderate POAG is defined as having an untreated IOP prior to treatment of >21mmHg and a repeatable visual field defect with a Mean Deviation of <12dB and/or documented but stable ONH appearance, consistent with a diagnosis of glaucoma.

Group 2P (n=36); Early to moderate, treated patients with normal tension glaucoma (NTG). Normal Tension Glaucoma is defined using the same criteria as POAG but with an untreated IOP of <21mmHg throughout the day. This group has NTG and is thought to be at increased risk of vascular dysfunction due to loss of ONH perfusion.

Group 3P (n=36); Early to moderate, treated patients with POAG or NTG with recurrent disc hemorrhage (indicative of progression).

3. DR study arm

DR patient groups are organised according to established risk factors for the clinical progression of DR (increasing from Groups 1 A to 3 A, ETDRS, 1991). We will recruit 41 patients per group (Klein et al, 1984).

Group 1D (n=41); Type 2 diabetic patients with no, or minimal, clinically visible DR. These patients are at low risk of developing sight-threatening DR.

Group 2D (n=41); Type 2 diabetic patients with microaneurysms and / or hard exudates within 2 disc diameters of the fovea and no clinical evidence of retinal thickening. These patients are at increased risk of developing DME.

Group 3D (n=41); Type 2 diabetic patients with the typical features of moderate-to-severe DR i.e. venous beading, intra-retinal microvascular abnormalities (IRMA) and dark blot intra-retinal haemorrhages. These patients are at a much increased risk of developing proliferative DR and/or ischemic maculopathy.


Detailed Description:

This research will add to our basic knowledge in predicting the development of sight-threatening change in patient with the ARMD, diabetic retinopathy and primary open glaucoma, and facilitate earlier detection of the problem to help us discover earlier treatments for people with these conditions. The reliability of each imaging technology will be assessed by determining its ability to differentiate between diseased and healthy eyes. Through this proposed Research Program, and in conjunction with our international academic and private sector partners, we will build and develop unique quantitative imaging technologies to:

  • Comprehensively assess the blood supply to, and vascular regulation characteristics of the posterior segment of the eye, a diagnostic capability that is currently severely limited.
  • Assess oxygen saturation disturbances in the retina and ON that occur prior to clinically detectable changes, diagnostic capability that currently does not exist
  • Using the retinal blood supply and oxygen saturation parameters, we will derive net oxygen delivery to the retina and optic nerve head (ONH), a diagnostic capability that does not exist.
  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The cohorts will be selected from the clinics of retinal and glaucoma specialists at the Toronto Western Hospital and will be identified from their charts. Clinicians will ask eligible patients whether they would be interested in participating.

Also flyers advertising the study will be posted at Toronto Western Hospital and anyone interested can contact the principal investigator.

Criteria

Inclusion criteria:

  • Subjects diagnosed with age related macular degeneration
  • Subjects diagnosed with glaucoma
  • Subjects diagnosed with diabetic retinopathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01348672

Contacts
Contact: Chris Hudson, Ph.D 416 603 5694 chudson@uwaterloo.ca

Locations
Canada, Ontario
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Chris Hudson, Ph.D    416 603 5694    chudson@uwaterloo.ca   
Sponsors and Collaborators
University of Toronto
Ontario Research Fund
Investigators
Principal Investigator: Christopher Hudson, OD, PhD Toronto Western Hospital, Toronto Western Research Institute, University of Toronto, University of Waterloo
  More Information

Publications:
Responsible Party: Chris Hudson, Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT01348672     History of Changes
Other Study ID Numbers: ORF2
Study First Received: February 27, 2011
Last Updated: January 16, 2013
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University of Toronto:
Age related macular degeneration
Glaucoma
Diabetic retinopathy
Retinal oxygen saturation
Blood flow
Vascular function
High resolution imaging

Additional relevant MeSH terms:
Glaucoma
Macular Degeneration
Retinal Diseases
Diabetic Retinopathy
Ocular Hypertension
Eye Diseases
Retinal Degeneration
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on October 19, 2014