Longitudinal Observational Study of Diabetic Retinopathy Progression in Type 2 Diabetes Patients

NCT07458516 | Recruiting

• 1 other identifier: 4C-2025-17
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical study is to explore imaging, functional and systemic biomarkers of diabetic retinopathy (DR) progression, in Type 2 Diabetes (T2D) patients with moderate to severe non-proliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (PDR) using state of the art methodologies, commonly applied in clinical practice, over a period of two years. This study will provide longitudinal data to better understand retinal changes in moderate to severe diabetic retinopathy and early proliferative diabetic retinopathy and help guide timely interventions to prevent vision loss.

Conditions

Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diabetic Complication; Retinal Disease

Keywords

Disease biomarkers

Outcome Measures

Primary Outcomes (14)

• Changes in capillary skeletonized vessel density (SVD)

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in capillary non-perfusion using skeletonized vessel density (SVD) in the superficial and deep retinal vascular layers assessed with Optical Coherence Tomography Angiography.

  Baseline to 24 months

• Changes in capillary perfusion density (PD) using OCTA

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in capillary non-perfusion using binarized vessel density (VD) as perfusion density (PD) in the superficial and deep retinal vascular layers assessed with Optical Coherence Tomography Angiography.

  Baseline to 24 months

• Foveal Avascular Zone (FAZ) area

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in the area of the foveal avascular zone measured in square millimeters (mm²) using Optical Coherence Tomography Angiography automated segmentation tools across DRSS levels.

  Baseline to 24 months

• Foveal Avascular Zone (FAZ) perimeter

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in the perimeter of the foveal avascular zone measured in millimeters (mm) using Optical Coherence Tomography Angiography automated segmentation tools across DRSS levels.

  Baseline to 24 months

• Foveal Avascular Zone (FAZ) circularity

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in the circularity of the foveal avascular zone using Optical Coherence Tomography Angiography automated segmentation tools across DRSS levels.

  Baseline to 24 months

• Changes in retinal ischemic area using UWF FFA

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in retinal ischemic area (mm2) across DRSS levels.

  Baseline to 24 months

• Changes in central retinal thickness (CRT)

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in Central Retinal Thickness (CRT) assessed using Optical Coherence Tomography (OCT) across DRSS levels.

  Baseline to 24 months

• Changes in central intraretinal fluid

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in intraretinal fluid (layer-specific) assessed using Optical Coherence Tomography (OCT) across DRSS levels.

  Baseline to 24 months

• Changes in Disorganisation of Retinal Inner Layers (DRIL)

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in Disorganisation of Retinal Inner Layers (DRIL) assessed using Optical Coherence Tomography (OCT) across DRSS levels.

  Baseline to 24 months

• Changes in Disorganisation of Retinal Outer Layers (DROL)

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in Disorganisation of Retinal Outer Layers (DROL) assessed using Optical Coherence Tomography (OCT) across DRSS levels.

  Baseline to 24 months

• Changes in Ganglion Cell Layer (GCL) + Inner Plexiform Layer (IPL) thickness

  Evaluate baseline differences and longitudinal changes (from baseline to month 24) in Ganglion Cell Layer (GCL) + Inner Plexiform Layer (IPL) thickness assessed using Optical Coherence Tomography (OCT) across DRSS levels.

  Baseline to 24 months

• DRSS severity level

  Evaluate the DRSS score (range 10-85; higher scores indicate worse severity) in Ultra-widefield fundus photography (UWF-FP).

  Baseline to 24 months

• Changes in microaneurysm (MA) count

  Evaluate baseline differences and longitudinal changes (from baseline to months 6, 12, and 24) in MA number in colour fundus photography (CFP field 2) across DRSS levels.

  Baseline to 24 months

• Changes in microaneurysm (MA) turnover

  Evaluate baseline differences and longitudinal changes (from baseline to months 6, 12, and 24) in MA turnover in colour fundus photography (CFP field 2) across DRSS levels.

  Baseline to 24 months

Secondary Outcomes (5)

• Changes in DRSS levels

  Baseline to 24 months

• Changes in Best Corrected Visual Acuity (BCVA)

  Baseline to 24 months

• Retinal sensitivity using MAIA Microperimetry

  Baseline to 24 months

• Changes in Intraretinal Microvascular Abnormalities (IRMAs)

  Baseline to 24 months

• Changes in neovascularization (NV)

  Baseline to 24 months

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study Population: Patients with moderate to severe NPDR and mild PDR. Ideally, the distribution of participants will be as follows: 40 for Diabetic Retinopathy Severity Scale (DRSS) level 43, 40 for DRSS level 47, and 20 for DRSS levels 53-61

You may qualify if:

• Type 2 diabetes mellitus (T2D) according to 1985 World Health Organization (WHO) criteria.
• Age between 35 and 80 years.
• Best-corrected visual acuity (BCVA) ≥ 69 letters (20/40).
• Refraction with a spherical equivalent less than 5 diopters.
• Non-proliferative diabetic retinopathy (NPDR; DRSS levels 43, 47, 53) or mild proliferative diabetic retinopathy (PDR; DRSS level 61: Neovascularization Elsewhere (NVE) \< ½ disc area in ≥ 1 quadrant, no Neovascularization of the Disc (NVD), no vitreous or sub-hyaloid hemorrhage), in which panretinal photocoagulation (PRP) and/or intravitreal anti-VEGF treatment can safely be deferred for at least 6 months, based on consensus between patient and investigator - using ETDRS criteria, 7-field equivalent area on ultra-widefield fundus imaging.
• Ability to understand and sign the written Informed Consent Form (ICF).

You may not qualify if:

• Central subfield thickness (CST) \> 400 μm (fluid allowed if CST ≤ 400 μm and foveal contour is normal, as determined by the Central Reading Centre, and treatment is not immediately required).
• Any sign of retinal fibrovascular proliferation.
• Uncontrolled glaucoma (intraocular pressure \> 25 mmHg regardless of concomitant IOP-lowering medications) or neovascular glaucoma.
• Any sign of iris neovascularization, vitreous, or pre-retinal hemorrhage.
• Other retinal vascular diseases (ocular ischemic syndrome, retinal arterial or venous occlusion, exudative age-related macular degeneration, etc.).
• Previous panretinal photocoagulation (PRP) or intravitreal injection treatment.
• Significant media opacities including severe cataract, corneal scarring or edema, or vitreous hemorrhage that precludes fundus evaluation.
• Pupil dilation \< 5 mm.

Sponsors & Collaborators

• Association for Innovation and Biomedical Research on Light and Image: lead
• Fundação para a Ciência e a Tecnologia: collaborator

Study Sites (1)

AIBILI-CEC (AIBILI-Clinical Trial Centre)

Coimbra, 3000-548, Portugal

RECRUITING

Related Publications (3)

• Arjamaa O, Nikinmaa M. Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. Exp Eye Res. 2006 Sep;83(3):473-83. doi: 10.1016/j.exer.2006.01.016. Epub 2006 Jun 5.

  PMID: 16750526 BACKGROUND

• Willis JR, Doan QV, Gleeson M, Haskova Z, Ramulu P, Morse L, Cantrell RA. Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States. JAMA Ophthalmol. 2017 Sep 1;135(9):926-932. doi: 10.1001/jamaophthalmol.2017.2553.

  PMID: 28750122 BACKGROUND

• Whitehead M, Osborne A, Widdowson PS, Yu-Wai-Man P, Martin KR. Angiopoietins in Diabetic Retinopathy: Current Understanding and Therapeutic Potential. J Diabetes Res. 2019 Aug 14;2019:5140521. doi: 10.1155/2019/5140521. eCollection 2019.

  PMID: 31485452 BACKGROUND

MeSH Terms

Conditions

Diabetic Retinopathy; Diabetes Mellitus, Type 2; Diabetes Complications; Retinal Diseases

Condition Hierarchy (Ancestors)

Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Inês P Marques, MD PhD

  AIBILI - Associação para a Investigação Biomédica e Inovação em Luz e Imagem

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joana Tavares, PhD

CONTACT

+351239480137; jftavares@aibli.pt

Liliana C Soares, MsC

CONTACT

+351239480105/131; important_4c@aibili.pt

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 9, 2026
• Study Start: November 24, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

PT (1)