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| Name | Class |
|---|---|
| Fundação para a Ciência e a Tecnologia | OTHER |
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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:
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.
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Diabetic Retinopathy Staging | 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. | Baseline to 12 months |
| Diabetic Retinopathy (DR) Progression, measured on the OPTOS Ultra-widefield Fundus Photography (UWF-FP) | Defined as a ≥2-step worsening on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale (ETDRS DRSS) | Baseline to 12 months |
| Proportion of participants with ≥15-letter loss in ETDRS Best-Corrected Visual Acuity (BCVA) | ≥15-letter loss on the ETDRS BCVA chart (measured with Snellen or LogMAR charts converted to the ETDRS scale). | Baseline to 12 months |
| Incidence of Major Adverse Cardiovascular Events (MACE) | Incidence of myocardial infarction, ischemic stroke, or hospitalization for heart failure, extracted from medical history and confirmed by investigator. | Baseline to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of microaneurysms in the central ETDRS area (90°) | Count of microaneurysms within the central ETDRS grading area (90 degrees), assessed by human graders on Optos Ultra-Widefield Fundus Photography images. | Baseline to 12 months |
| Number of microaneurysms in the peripheral retina (90-200°) |
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Inclusion Criteria:
Exclusion Criteria:
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1.000 participants with T2D will be included in this study, in a recruitment period of 12 months.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joana F Tavares, PhD | Contact | 239480137 | alert_4c@aibili.pt | |
| Liliana C Soares, MsC | Contact | 239480115 | alert_4c@aibili.pt |
| Name | Affiliation | Role |
|---|---|---|
| Luís Mendes, PhD | Association for Innovation and Biomedical Research on Light and Image | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AIBILI-Clinical Trial Centre | Recruiting | Portugal | Coimbra District | 3000-548 | Portugal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34442470 | Background | Cunha-Vaz J, Mendes L. Characterization of Risk Profiles for Diabetic Retinopathy Progression. J Pers Med. 2021 Aug 23;11(8):826. doi: 10.3390/jpm11080826. | |
| 32408522 | Background | Marques IP, Madeira MH, Messias AL, Santos T, Martinho AC, Figueira J, Cunha-Vaz J. Retinopathy Phenotypes in Type 2 Diabetes with Different Risks for Macular Edema and Proliferative Retinopathy. J Clin Med. 2020 May 12;9(5):1433. doi: 10.3390/jcm9051433. |
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| ID | Term |
|---|---|
| D003930 | Diabetic Retinopathy |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
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Count of microaneurysms in the peripheral retinal area (between 90 and 200 degrees), assessed by human graders on Optos Ultra-Widefield Fundus Photography images. |
| Baseline to 12 months |
| Presence of hemorrhages in the central ETDRS area | 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. | Baseline to 12 months |
| Presence of peripheral retinal hemorrhages (90-200°) | 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. | Baseline to 12 months |
| Presence of exudates in the retina | Presence of hard exudates identified by human graders on Optos Ultra-Widefield Fundus Photography. Reported as the percentage of eyes displaying ≥1 exudate. | Baseline to 12 months |
| Presence of cotton wool spots in the retina | Presence of cotton wool spots identified by human graders on Optos Ultra-Widefield Fundus Photography. Reported as the percentage of affected eyes. | Baseline to 12 months |
| Correlation between retinal microaneurysm count and glycated hemoglobin (HbA1c) | 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). | Baseline to 12 months |
| Retinal vessel density | Quantitative vessel density measured using Optical Coherence Tomography Angiography. Expressed in inverse millimeters (mm-1) | Baseline to 12 months |
| Correlation between retinal vessel density and systolic blood pressure | Correlation between vessel density quantified using Optical Coherence Tomography Angiography and systolic blood pressure collected during clinical evaluation. Reported as a correlation coefficient (r). | Baseline to 12 months |
| Abnormal intercapillary spaces (AIS) in the retina | 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. | Baseline to 12 months |
| Correlation between abnormal intercapillary spaces (AIS) and major adverse cardiovascular events (MACE) | 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). | Baseline to 12 months |
| Retinal venous calibre | Mean venous calibre measured in micrometers (μm) through automated analysis of Color Fundus Photography images. | Baseline to 12 months |
| Retinal vascular tortuosity | Vascular tortuosity calculated from Color Fundus Photography images using validated image analysis algorithms. | Baseline to 12 months |
| Microaneurysm turnover (MAT) over one year | Number of microaneurysms appearing and disappearing over a one-year period, quantified through automated analysis of sequential Color Fundus Photography images. | Baseline to 12 months |
| Retinal fractal dimension | Fractal dimension of the retinal vascular network, calculated using an automated feature extraction applied to Color Fundus Photography images. | Baseline to 12 months |
| Foveal Avascular Zone (FAZ) metrics | Area of the foveal avascular zone measured in square millimeters (mm²) using Optical Coherence Tomography Angiography automated segmentation tools. | Baseline to 12 months |
| 38109709 | Background | Santos AR, Almeida AC, Rocha AC, Reste-Ferreira D, Marques IP, Cunha-Vaz Martinho A, Mendes L, Santos T, Lewis W, Cunha-Vaz J. CENTRAL AND PERIPHERAL INVOLVEMENT OF THE RETINA IN THE INITIAL STAGES OF DIABETIC RETINOPATHY. Retina. 2024 Apr 1;44(4):700-706. doi: 10.1097/IAE.0000000000004021. |
| 11583677 | Background | Sato Y, Lee Z, Hayashi Y. Subclassification of preproliferative diabetic retinopathy and glycemic control: relationship between mean hemoglobin A1C value and development of proliferative diabetic retinopathy. Jpn J Ophthalmol. 2001 Sep-Oct;45(5):523-7. doi: 10.1016/s0021-5155(01)00380-x. |
| 25704318 | Background | Silva PS, Cavallerano JD, Haddad NM, Kwak H, Dyer KH, Omar AF, Shikari H, Aiello LM, Sun JK, Aiello LP. Peripheral Lesions Identified on Ultrawide Field Imaging Predict Increased Risk of Diabetic Retinopathy Progression over 4 Years. Ophthalmology. 2015 May;122(5):949-56. doi: 10.1016/j.ophtha.2015.01.008. Epub 2015 Feb 19. |
| Background | IDF Diabetes Atlas 9th edition. (2019). IDF Diabetes Atlas 9th edition 2019. In International Diabetes Federation Diabetes Atlas, Ninth Edition. |
| Background | Marques, I., Mendes, L., & Cunha-Vaz, J. (2018). Noninvasive Multimodal Imaging of Diabetic Retinopathy (pp. 88-101). https://doi.org/10.1159/000487414 |
| D002318 |
| Cardiovascular Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |