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NCT Number: NCT07417410

Analysis of DR Progression to Identify Risks and Need for Treatment

The goal of this observational study is to understand whether vascular and structural changes in the eyes caused by diabetes can help predict which people are more likely to experience worsening diabetic retinopathy (a diabetes-related eye disease) and how these eye changes are related to cardiovascular complications.

The study will include about 1,000 people with type 2 diabetes, aged 35 to 90 years, and will take place over twelve months. It may also include a retrospective component, where existing medical and imaging data collected from previous visits (within the last 1 to 5 years) will be analyzed.

The main questions it aims to answer are:

* Can eye vessel and tissue changes, observed through modern imaging techniques and clinical data, help better describe and predict which cases of diabetic retinopathy will become more severe? * Can these same eye changes help predict the presence and risk of cardiovascular problems-such as heart disease or stroke-in people living with type 2 diabetes?

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Key information

Conditions

Diabetic Retinopathy Cardiovascular Diseases Diabetes Complications Diabetes Mellitus Diabetic Angiopathies Endocrine System Diseases Eye Diseases Retinal Diseases Vascular Diseases

Age range

35 year–90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

AIBILI-Clinical Trial Centre

Portugal, Coimbra District, 3000-548

Location status: Recruiting

Location contact

Inês P Marques, MD, PhD

CONTACT

[email protected]

239480124

About this study

Diabetic Retinopathy (DR) is a leading cause of vision loss in adults with type 2 diabetes (T2D) and is associated with systemic complications, including cardiovascular disease. Early identification of patients at high risk of DR progression and cardiovascular events is critical to optimizing clinical management. Retinal imaging biomarkers, combined with clinical and demographic data, provide an opportunity to better understand disease mechanisms, predict progression of DR and associated cardiovascular complications, and guide personalized interventions.

The aim of this study is to investigate the influence of central versus peripheral retinal lesions on DR progression and staging, characterize associations between retinal biomarkers and cardiovascular risk factors and major adverse cardiovascular events (MACE), and contribute to the understanding of pathophysiological mechanisms underlying DR in T2D patients. The study will also generate a high-quality, harmonized database to support the development of artificial intelligence (AI) models.

This study aims to determine the extent to which central and peripheral retinal lesions, together with quantitative imaging biomarkers, contribute to the progression and staging of DR and the occurrence of cardiovascular complications in patients with T2D. Additionally, in the scope of the ALERT project (supported by Fundação para Ciência e Tecnologia (FCT); COMPETE2030-FEDER-00921900), the data of this clinical study will be used to create a harmonized, high-quality database for the development of exploratory interpretable artificial intelligence models for predicting DR progression and stage as well as predict the values of cardiovascular risk factors, and the risk of developing cardiovascular complications.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosed with type 2 diabetes according to the 1985 WHO criteria.
  • Age between 35 and 90 years.
  • Retrospective visit or referenced patients. For the retrospective visit, a documented follow-up of 1-5 years is required, with at least one clinical visit. For the referenced patients, it is required that they have either diabetic retinopathy at the baseline visit, the presence of at least one cardiovascular risk factor at the baseline visit, or cardiovascular complications at the baseline visit.
  • Signed informed consent.

Exclusion criteria

  • Previous laser photocoagulation or intravitreal injections (consider if corticosteroids were administered).
  • Presence of clinically significant macular edema (CSME) with vision loss or requiring immediate treatment.
  • Proliferative diabetic retinopathy.
  • Any ocular surgery within the previous 3 months.
  • Renal Replacement Therapy (Hemodialysis, Peritoneal Dialysis).
  • Severe systemic illness, subject to investigator's judgment.

Treatment and study plan

Primary outcomes

  1. Change in Diabetic Retinopathy Staging

    Time frame: Baseline to 12 months

    Change in score on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS DRSS; range 10-85; higher scores indicate worse severity), measured on Optos Ultra-Widefield Fundus Photography.

  2. Diabetic Retinopathy (DR) Progression, measured on the OPTOS Ultra-widefield Fundus Photography (UWF-FP)

    Time frame: Baseline to 12 months

    Defined as a ≥2-step worsening on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS DRSS)

  3. Proportion of participants with ≥15-letter loss in ETDRS Best-Corrected Visual Acuity (BCVA)

    Time frame: Baseline to 12 months

    ≥15-letter loss on the ETDRS BCVA chart (measured with Snellen or LogMAR charts converted to the ETDRS scale).

  4. Incidence of Major Adverse Cardiovascular Events (MACE)

    Time frame: Baseline to 12 months

    Incidence of myocardial infarction, ischemic stroke, or hospitalization for heart failure, extracted from medical history and confirmed by investigator.

Secondary outcomes

  1. Number of microaneurysms in the central ETDRS area (90°)

    Time frame: Baseline to 12 months

    Count of microaneurysms within the central ETDRS grading area (90 degrees), assessed by human graders on Optos Ultra-Widefield Fundus Photography images.

  2. Number of microaneurysms in the peripheral retina (90-200°)

    Time frame: Baseline to 12 months

    Count of microaneurysms in the peripheral retinal area (between 90 and 200 degrees), assessed by human graders on Optos Ultra-Widefield Fundus Photography images.

  3. Presence of hemorrhages in the central ETDRS area

    Time frame: Baseline to 12 months

    Presence of retinal hemorrhages within the central ETDRS grading area (90 degrees), identified by human graders on Optos Ultra-Widefield Fundus Photography. Reported as the percentage of affected eyes.

  4. Presence of peripheral retinal hemorrhages (90-200°)

    Time frame: Baseline to 12 months

    Presence of retinal hemorrhages in the peripheral retina (90-200 degrees), assessed through human grading of Optos Ultra-Widefield Fundus Photography images. Reported as the percentage of affected eyes.

  5. Presence of exudates in the retina

    Time frame: Baseline to 12 months

    Presence of hard exudates identified by human graders on Optos Ultra-Widefield Fundus Photography. Reported as the percentage of eyes displaying ≥1 exudate.

  6. Presence of cotton wool spots in the retina

    Time frame: Baseline to 12 months

    Presence of cotton wool spots identified by human graders on Optos Ultra-Widefield Fundus Photography. Reported as the percentage of affected eyes.

  7. Correlation between retinal microaneurysm count and glycated hemoglobin (HbA1c)

    Time frame: Baseline to 12 months

    Correlation between the number of microaneurysms identified on Optos Ultra-Widefield Fundus Photography and (HbA1c) levels obtained through clinical laboratory testing. Reported as a correlation coefficient (r).

  8. Retinal vessel density

    Time frame: Baseline to 12 months

    Quantitative vessel density measured using Optical Coherence Tomography Angiography. Expressed in inverse millimeters (mm-1)

  9. Correlation between retinal vessel density and systolic blood pressure

    Time frame: Baseline to 12 months

    Correlation between vessel density quantified using Optical Coherence Tomography Angiography and systolic blood pressure collected during clinical evaluation. Reported as a correlation coefficient (r).

  10. Abnormal intercapillary spaces (AIS) in the retina

    Time frame: Baseline to 12 months

    Count of abnormal intercapillary spaces assessed using Optical Coherence Tomography Angiography automated analysis tools. Expressed as the percentage of pixels associated with the presence of abnormal intercapillary spaces relative to the total number of pixels in the slab.

  11. Correlation between abnormal intercapillary spaces (AIS) and major adverse cardiovascular events (MACE)

    Time frame: Baseline to 12 months

    Correlation between the number of abnormal intercapillary spaces measured on Optical Coherence Tomography Angiography and the occurrence of (MACE). Reported as a correlation coefficient (r).

  12. Retinal venous calibre

    Time frame: Baseline to 12 months

    Mean venous calibre measured in micrometers (μm) through automated analysis of Color Fundus Photography images.

  13. Retinal vascular tortuosity

    Time frame: Baseline to 12 months

    Vascular tortuosity calculated from Color Fundus Photography images using validated image analysis algorithms.

  14. Microaneurysm turnover (MAT) over one year

    Time frame: Baseline to 12 months

    Number of microaneurysms appearing and disappearing over a one-year period, quantified through automated analysis of sequential Color Fundus Photography images.

  15. Retinal fractal dimension

    Time frame: Baseline to 12 months

    Fractal dimension of the retinal vascular network, calculated using an automated feature extraction applied to Color Fundus Photography images.

  16. Foveal Avascular Zone (FAZ) metrics

    Time frame: Baseline to 12 months

    Area of the foveal avascular zone measured in square millimeters (mm²) using Optical Coherence Tomography Angiography automated segmentation tools.

Study contacts

Contact information is provided by the study sponsor or research team.

Joana F Tavares, PhD

CONTACT

[email protected]

239480137

Liliana C Soares, MsC

CONTACT

[email protected]

239480115

Sponsors and collaborators

Lead sponsor

Association for Innovation and Biomedical Research on Light and Image

Other

Collaborators

  • Fundação para a Ciência e a Tecnologia

Registry information

Acronym: ALERT

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Feb 18, 2026
Registry last updated
Mar 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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