PROGRESS10: 10-year Progression of Diabetic Retinopathy: Identification of Signs and Surrogate Outcomes

Association for Innovation and Biomedical Research on Light and Image (Other)
Overall Status
Recruiting ID

Study Details

Study Description

Brief Summary

To characterize both functionally and morphologically initial Diabetic Retinopathy (DR) stages and their progression over a period of 10 years.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Diabetic retinopathy (DR) is the most frequent complication of diabetes mellitus and the leading cause of legal blindness in active populations of industrialized countries. Progression of DR has been up to now classified according to the ETDRS classification, based on a multicentric study that evaluated the effect of laser photocoagulation on advanced stages of DR. Although appropriate for late stages of DR, it does not grade progression well in the initial stages of the disease. Initial stages of DR require urgent characterization and their evolution should be well defined because some of the lesions are still reversible.

    The early stages of DR are characterized by 4 main alterations: microaneurysms (MA) and retinal hemorrhages, represented by red dots in the fundus, blood-retinal barrier breakdown, capillary closure and damage of neuronal and glial cells of the retina. Thus, there are both microvascular changes, with endothelial cell and pericyte damage with thickening of basement membrane, and neuronal changes.

    Based on previous studies, progression of DR does not occur at the same rate in all patients. Some never develop vision loss, whereas others rapidly progress to macular edema or neovascularization leading to vision loss. The understanding of the mechanisms that balance in different direction is of outmost importance. The duration of diabetes mellitus and the metabolic control are major risk factors for DR progression, but they are insufficient to explain the great variability observed in patients.

    Recent data indicate that MA turnover may be an appropriate indicator of DR progression. Our research group has identified different DR progression phenotypes. Phenotype A is characterized by a low MA turnover, phenotype B characterized by increased thickness and phenotype C with predominant ischemia, with a high MA turnover. These phenotypes were defined based on MA turnover (RetmarkerDR) and on central retinal thickness (RT) measured by Optical Coherence Tomography (OCT) and the model was able to correctly identify eyes at risk of progression. 61,8-76,7% of eyes with an increase RT in the central subfield, inner and/or outer ring allowed a MA formation rate ≥ 2 and/or a MA turnover ≥ 6. More recently, some genetic variants have been linked to the different phenotypes and may explain specific progression patterns.

    There is emerging evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR and that it could participate in the development of microvascular abnormalities. The understanding of the underlying mechanisms leading to neurodegeneration and the identification of the mediators between neurodegeneration and microangiopathy is essential.

    The Investigators aim to understand the extent of these cell abnormalities in the initial stages of DR and to characterize their progression.

    Analysis of retinal thickness using OCT offers non-invasive evaluation of retinal edema and can suggest an appropriate treatment target. The Investigators will use recent and innovative approaches as Spectral domain OCT (SD-OCT) with retinal layers segmentation to study neurodegenerative changes occurring in DR. OCT-Angiography and OCT-Leakage layer by layer analysis will be used for microvasculature and blood retinal barrier assessment.

    Study Design

    Study Type:
    Observational [Patient Registry]
    Anticipated Enrollment :
    212 participants
    Observational Model:
    Time Perspective:
    Official Title:
    10-year Progression of Diabetic Retinopathy: Identification of Signs and Surrogate Outcomes
    Actual Study Start Date :
    Jun 1, 2021
    Anticipated Primary Completion Date :
    Dec 31, 2023
    Anticipated Study Completion Date :
    Dec 31, 2023

    Outcome Measures

    Primary Outcome Measures

    1. Phenotypic classification of DR in a 5-year period [5 years]

      Presence CME (Central Macular Edema) or PDR (Proliferative Diabetic Retinopathy)

    2. DR severity level [5 years]

      Early Treatment Diabetic Retinopathy Study Research Group, grading (7 fields-CFP)

    Secondary Outcome Measures

    1. Choroidal thickness analysis [5 years]

      Choroidal thickness assessed by Enhanced Depth Imaging (EDI) SD-OCT

    2. Retinal thickness analysis [5 years]

      Retinal thickness (RT) in central subfield, inner and outer rings, assessed by SD-OCT and using layer-by-layer segmentation

    3. Ellipsoid zone analysis [5 years]

      Degree of integrity of the ellipsoid zone, assessed by SD-OCT

    4. SD- OCT- Angiography analysis [5 years]

      Vessel analysis, assessed by SD-OCT OCT-Angiography

    5. OCT-Leakage analysis [5 years]

      LOR (low optical reflectivity) ratio in central subfield, inner and outer ring for assessment of BRB breakdown, assessed by OCT-Leakage

    6. Retinal thickness quantification [5 years]

      Retinal nerve fiber layer thickness (RNFL) and ganglion cells layer (GCL) + inner plexiform layer thickness (IPL) thickness, assessed by layer-by-layer SD-OCT

    7. mfERG assessement [5 years]

      P1 implicit time and P1 amplitude by ring

    Eligibility Criteria


    Ages Eligible for Study:
    35 Years to 80 Years
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Subjects who have participated in the PROGRESS study;

    • Subjects capable of understanding the information about the study and to give their informed consent to enter the study.

    • Subjects willing and able to comply with the study

    Exclusion Criteria:
    • Inadequate ocular media and/ or pupil dilatation that interfere with fundus examinations

    Contacts and Locations


    Site City State Country Postal Code
    1 AIBILI - Association for Innovation and Biomedical Research on Light and Image Coimbra Portugal 3000-548

    Sponsors and Collaborators

    • Association for Innovation and Biomedical Research on Light and Image


    • Principal Investigator: Inês P Marques, MD, AIBILI - Association for Innovation and Biomedical Research on Light and Image

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Association for Innovation and Biomedical Research on Light and Image Identifier:
    Other Study ID Numbers:
    • CEC/011/20
    First Posted:
    Dec 2, 2020
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 2, 2022