Phenotypes of Nonproliferative Diabetic Retinopathy in DM 2 Patients Identified by OCT, CFP, RLA and mfERG (DIAMARKER)

Phenotypes of Nonproliferative Diabetic Retinopathy in Diabetes Type 2 Patients Identified by Optical Coherence Tomography, Colour Fundus Photography, Fluorescein Leakage and Multifocal Electrophysiology (DIAMARKER Project: Genetic Susceptibility for Multi-systemic Complications in Diabetes Type-2: New Biomarkers for Diagnostic and Therapeutic Monitoring).

To characterise phenotypes of Non Proliferative Diabetic Retinopathy (NPDR) progression using multimodal testing/imaging procedures.

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy; Type-2 Diabetes

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Portugal
  • Coimbra, Portugal, 3000-548
    • AIBILI - Clinical Trials Centre (CEC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of 20 patients, male and female over 18 years-old, with type-2 diabetes mellitus and NPDR with signs of DR progression (RT increase and/or MA turnover) (according to the inclusion/exclusion criteria).

Description

Inclusion Criteria:

1. Age over 18 years-old.
2. Diabetes mellitus type 2 according to 1985 WHO criteria.
3. Non-proliferative diabetic retinopathy (ETDRS level <= 35)

4. Signs of NPDR progression based on existing clinical information:

   1. Retinal thickness (RT) increase (increase in RT above normal range as measured by OCT, considering the macular thickness normative data) in the central subfield, the inner ring and/or the outer ring (leaking phenotype); OR
   2. Neovascular disease activity as shown by microaneurysms (MA) turnover (MA formation rate >= 2, i.e. number of new MA per year) computed from CFP using the RetmarkerDR software (ischemic phenotype).
5. Informed consent.

Exclusion Criteria:

1. Cataract or other eye disease that may interfere with fundus examinations
2. Any eye surgery or treatment within a period of 6-months.
3. Pregnant or nursing (lactating) women.
4. Patients with chronic or severe kidney disease (glomerular filtration rate, GFR < 30 mL/min/1.73m2).
5. Patients with acute kidney injury.
6. Patients with known allergic or hypersensitivity reactions to gadolinium, versetamide or any of the inert ingredients.
7. Patients around the time of liver transplantation..
8. Patients with implants containing metals.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Leaking Phenotype; Retinal thickness (RT) increase (increase in RT above normal range as measured by OCT, considering the macular thickness normative data) in the central subfield, the inner ring and/or the outer ring.
Ischemic Phenotype; Neovascular disease activity as shown by microaneurysms (MA) turnover (MA formation rate >= 2, i.e. number of new MA per year) computed from CFP using the RetmarkerDR software.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multimodal testing/imaging procedures - Ophthalmological Imaging	Retinal thickness measured with OCT;	24 months
Multimodal testing/imaging procedures - Ophthalmological Imaging	MA turnover computed based on CFP.	24 months
Multimodal testing/imaging procedures - Ophthalmological Imaging	Macular area with increased retinal fluorescein leakage based on RLA.	12 months
Multimodal testing/imaging procedures - Ophthalmological Imaging	Implicit time local and ring amplitudes measured with mfERG.	12 months
Multimodal testing/imaging procedures - Psychophysical Testing	Psychophysical tests for speed discrimination, achromatic contrast, and chromatic contrast.	12 months
Multimodal testing/imaging procedures - Barin Imaging	Perfusion change measured with ASL.	12 months
Multimodal testing/imaging procedures - Ophthalmological Imaging	Blood-Brain Barrier alterations assessed contrast agent with Dynamic MR.	12 months
Multimodal testing/imaging procedures - Brain Imaging	Metabolite concentrations assessed with MR Spectroscopy.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multimodal testing/ imaging modalities (raw data)	Raw data obtained from the different modalities (OCT,MA turnover, RLA,mfERG, psychophysical tests, ASL, Dynamic MR and MR Spectroscopy).	24 months

Collaborators and Investigators

• Sponsor: Association for Innovation and Biomedical Research on Light and Image
• Collaborators: University of Coimbra
• Investigators: Study Chair: Miguel Castelo-Branco, MD PhD, FMUC; Principal Investigator: Luísa Ribeiro, MD MSc, Aibili - Cec

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 23, 2011
• First Posted (ESTIMATE): September 26, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 8, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: 4C-2011-01