Characterization of Retinal Vascular Disease in Eyes With Mild to Moderate NPDR in Diabetes Type 2

NCT ID: NCT03696810

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-30
• Study Completion Date: 2022-06-29

Brief Summary

Characterization of Retinal vascular disease in eyes with mild to moderate NPDR in Diabetes type 2, using novel non-invasive Imaging methods, in a longitudinal, prospective and interventional clinical Study with 2 years of duration (CORDIS).

Detailed Description

Diabetic Retinopathy (DR) is a frequent complication of Diabetes Mellitus (DM) and is the main cause of vision loss in the working population in western countries.

Several studies provided evidence that good diabetic control is important to prevent and delay disease progression, but while some patients develop sight-threatening DR (STDR) despite good control, others escape the development of vison loss with poor metabolic control.

The STDR is defined as DME and PDR. DME is defined as thickening of the macula and is mainly due to accumulation of fluid in the central macular area resulting mainly from fluid leakage due to the alterations of the BRB. Identifying the eyes/patients at risk to develop central involved macular edema (CIME) and consequent vision-loss, as well as to understand its causes is fundamental for its appropriate treatment and, finally, to avoid vision loss due to DME.

Several studies have shown different prevalence's of DR, ranging from 10.1% to 48.1%.

The prevalence of DM in Portugal has increased and, between patients aged 20 to 79 years, was 11.7% in 2009, reaching 13.3% in 2013.

Chronic diseases often begin with a symptom-free phase being biomarkers fundamental in the identification of high-risk individuals in a reliably and timely manner, so that they can either be treated before onset of the disease or as soon as possible.

Our group has identified 3 different phenotypes of progression based on the microaneurysm (MA) turnover rate (sum of MA formation and disappearance rates) and central retinal thickness (RT) measurements obtained using non-invasive repeatable procedures: digital color fundus photography (CFP) and optical coherence tomography (OCT). MA turnover can identify eyes at risk of progression to Clinically Significant Macular Edema (CSME), as shown by our research results and an independent group. RT obtained with OCT provides insight into morphological changes of the retina in DR and DME, allowing the detection of retinal edema.

The current study will address only two of the published phenotypes, B and C, which show more rapid progression to STDR.

For an improved characterization of the main microvascular alterations that occur in NPDR, the investigators will use novel noninvasive, direct, objective and quantitative OCT-based methodologies: Optical coherence tomography angiography (OCTA) and OCT-Leakage (OCT-L).

OCTA allows the construction of three-dimensional blood flow information, and therefore can serve as a method to evaluate ocular circulation. OCTA is non-invasive and has the potential to be superior to fluorescein angiography (FA) in the detection and follow-up of DR lesions and mean vessel density measured in the superficial retinal layer in OCTA revealed to be a good differentiator between healthy eyes and eyes with DR. Vessel density was also correlated with best corrected visual acuity (BCVA) and severity of DR, suggesting that capillary closure may provide relevant information regarding progression of DR in individual patients with DM and may be a potential indicator for vision loss.

OCT-Leakage (OCT-L) is a new non-invasive imaging technique that performs automated analysis of the retinal extracellular space using spectral-domain optical coherence tomography (SD-OCT). Abnormal fluid accumulation is an indicator of breakdown of the blood-retinal barrier (BRB), which is an early and frequent finding in DR. Our research group showed the importance of this new method and demonstrated the increased sensitivity of OCT-L to detect abnormal fluid in the retina when compared with FA. This can be particularly useful to better characterize and identify features associated to leaky phenotype B.

A major objective of this study is to investigate changes in OCTA and OCT-L that may be biomarkers in the diagnosis and progression of NPDR and its ability to distinguish different stages of the disease. The identification with OCT-L of the abnormal fluid and alteration of the blood-retinal barrier (BRB), its location and quantification, complementing conventional OCTA, providing, therefore, information on capillary closure, vascular morphology and their alterations over 2 years, are expected to contribute to our understanding of DR progression.

Validation of biomarkers of DR progression, such as MA turnover and RT are important steps. However, OCTA and OCT-L offer an opportunity of improved characterization of the different DR phenotypes.

This study intends to better characterize the main alterations of the different phenotypes of DR considered to be leaky (OCT-L) or ischemic (OCTA), and to identify patients at risk of progression to STDR, identified in this study as central-involved ME (CIME), objectively measured by OCT or development of PDR, using these recent non-invasive techniques: OCTA and OCT-L.

Conditions

NPDR - Non Proliferative Diabetic Retinopathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

• Laboratory tests

• Laboratory tests (HbA1C levels and lipids)

Group Type: OTHER

Laboratory tests

Intervention Type: DIAGNOSTIC_TEST

• Laboratory tests (HbA1C levels and lipids)

Interventions

Laboratory tests

• Laboratory tests (HbA1C levels and lipids)

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Exclusion Criteria

• Cataract or other eye disease that may interfere with fundus examinations.
• Glaucoma.
• Any eye surgery within a period of 6-months before the screening visit date.
• Other retinal vascular disease.
• Previous laser or intravitreal injection treatment.
• Dilatation of the pupil < 5 mm.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação para a Ciência e a Tecnologia

OTHER

Sponsor Role: collaborator

Association for Innovation and Biomedical Research on Light and Image

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

AIBILI- Association for Biomedical Research and Inovation on Light and Image.

Coimbra, , Portugal

Countries

Portugal

References

Marques IP, Ribeiro ML, Santos T, Reste-Ferreira D, Mendes L, Martinho AC, Santos AR, Figueira J, Lobo C, Cunha-Vaz J. Patterns of Progression of Nonproliferative Diabetic Retinopathy Using Non-Invasive Imaging. Transl Vis Sci Technol. 2024 May 1;13(5):22. doi: 10.1167/tvst.13.5.22.

Reference Type: DERIVED

PMID: 38780953 (View on PubMed)

Other Identifiers

CEC/194/18

Identifier Type: -

Identifier Source: org_study_id