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

NCT ID: NCT01348672

Last Updated: 2013-01-17

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 381 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2015-08-31

Brief Summary

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.

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.

Conditions

Age Related Macular Degeneration; Glaucoma; Diabetic Retinopathy.

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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).

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Subjects diagnosed with age related macular degeneration
• Subjects diagnosed with glaucoma
• Subjects diagnosed with diabetic retinopathy

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ontario Research Fund

OTHER

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: lead

Responsible Party

Chris Hudson

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher Hudson, OD, PhD

Role: PRINCIPAL_INVESTIGATOR

Toronto Western Hospital, Toronto Western Research Institute, University of Toronto, University of Waterloo

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Chris Hudson, Ph.D

Role: CONTACT

chudson@uwaterloo.ca

416 603 5694

Facility Contacts

Chris Hudson, Ph.D

Role: primary

chudson@uwaterloo.ca

416 603 5694

References

Bressler NM, Bressler SB, Congdon NG, Ferris FL 3rd, Friedman DS, Klein R, Lindblad AS, Milton RC, Seddon JM; Age-Related Eye Disease Study Research Group. Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11. Arch Ophthalmol. 2003 Nov;121(11):1621-4. doi: 10.1001/archopht.121.11.1621.

Reference Type: BACKGROUND

PMID: 14609922 (View on PubMed)

Klein R, Wang Q, Klein BE, Moss SE, Meuer SM. The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity. Invest Ophthalmol Vis Sci. 1995 Jan;36(1):182-91.

Reference Type: BACKGROUND

PMID: 7822146 (View on PubMed)

Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):823-33.

Reference Type: BACKGROUND

PMID: 2062515 (View on PubMed)

Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol. 1984 Apr;102(4):527-32. doi: 10.1001/archopht.1984.01040030405011.

Reference Type: BACKGROUND

PMID: 6367725 (View on PubMed)

Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E; Early Manifest Glaucoma Trial Group. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003 Jan;121(1):48-56. doi: 10.1001/archopht.121.1.48.

Reference Type: BACKGROUND

PMID: 12523884 (View on PubMed)

Other Identifiers

ORF2

Identifier Type: -

Identifier Source: org_study_id