Diabetic RetinopathyIMPORTANTNCT07458516
Longitudinal Observational Study of Diabetic Retinopathy Progression in Type 2 Diabetes Patients
An observational study of Diabetic Retinopathy and Diabetes Mellitus, Type 2, run by Association for Innovation and Biomedical Research on Light and Image at 1 site in Portugal.
Trial summary
The purpose of this clinical study is to explore structural and functional imaging and systemic biomarkers of diabetic retinopathy (DR) progression, in eyes from Type 2 Diabetes (T2D) patients with moderate to severe non-proliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (PDR) using… Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Diabetic Retinopathy, Diabetes Mellitus, Type 2, Diabetic Complication
- How many people
- 100 participants
- Where
- 1 sitePortugal
- Study dates
- 24 Nov 2025to Nov 2028
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Study Population: Eyes with moderate to severe NPDR and mild PDR. Ideally, the distribution of eyes 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
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 9Show fewer
- Any eye surgery within 6 months prior to the inclusion visit.
- Significant media opacities including severe cataract, corneal scarring or edema, or vitreous hemorrhage that precludes fundus evaluation.
- Pupil dilation < 5 mm.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal1 site, 1 recruiting
- Recruiting
AIBILI-CEC (AIBILI-Clinical Trial Centre)
Coimbra, 3000-548
Inês P Marques, MD PhD, +351 239 480 124, ipmarques@aibili.pt
Joana Tavares, PhD, +351 239 480 137, jftavares@aibili.pt
About this study
Official title: IMaging Pre-PrOlifeRative sTAge of Diabetic retiNopaThy to Guarantee Timely Treatment - IMPORTANT
The purpose of this clinical study is to explore structural and functional imaging and systemic biomarkers of diabetic retinopathy (DR) progression, in eyes from 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. One or two eligible eyes per participant may be included in the study. The study will evaluate retinal vascular closure, ischemia, leakage, neurodegeneration, macular edema and microaneurysm dynamics and their association with disease progression.
Read the detailed description
Diabetes Mellitus (DM) is an important public health problem, affecting about 589 million people in the world, and expected to reach 853 million by 2050. Active screening for DR is important because most patients may be asymptomatic until the very late stages. Nonproliferative diabetic retinopathy (NPDR) itself may be associated with reduced visual function and quality of life measures (Willis et al., 2017).
The molecular pathophysiology of DR is complex, and a complete model of the disease is still being elucidated. The oxidative stress in diabetes upregulates multiple cytokines and chemokines, such as vascular endothelial growth factor (VEGF), angiopoietins, tumour necrosis factor (TNF), interleukins (ILs) and matrix metalloproteinases (MMPs) that leads to breakdown of the blood-retinal-barrier (BRB). Also, retinal capillary obstruction (leukostasis) or dropout (apoptosis of vascular cells) in diabetes leads to tissue ischemia and hypoxia causing increased retinal VEGF expression through transcriptional regulation by hypoxia-inducible factor 1 alpha (HIF-1α) (Arjamaa \& Nikinmaa, 2006; Whitehead et al., 2019).
The risk of developing DR complications increases over time, with increasing areas of capillary nonperfusion underpinning progression to more severe forms and development of complications as PDR or diabetic macular edema (DME), driven by hypoxia and hyperexpression of proangiogenic growth factors. However, this risk varies widely, independently of metabolic control. Differentiating patients with higher risk of progression and development of vision-threatening complications (VTC; DME and PDR) is of paramount importance for efficient treatment of the disease in order to prevent vision disability and achieve better visual outcomes. Recent developments in terms of retina imageology, namely Optical Coherence Tomography (OCT) and OCT Angiography (OCTA), have improved the understanding of DR pathophysiology and evolution, with a better characterization of venous abnormalities including occlusion, tortuosity, dilatation, looping or beading. OCTA examination is faster and safer compared to examination with fluorescein angiography (FA), and it can visualise the retinal vasculature in any layer of the retina. OCTA has the potential to become the examination of choice to identify eyes at risk of progression and development of VTC. Ultra-widefield fluorescein angiography (UWF-FFA) further enables the assessment of retinal ischemia and retinal leakage over a wider retinal area, providing additional biomarkers of disease severity and progression.
The purpose of this observational, non-interventional, prospective, and longitudinal clinical study is to explore explore structural and functional imaging and systemic biomarkers of diabetic retinopathy (DR) progression, in eyes from Type 2 Diabetes (T2D) patients with moderate to severe NPDR and mild PDR - Diabetic Retinopathy Severity Scale (DRSS) levels 43, 47, 53, and 61 - using state of the art methodologies, commonly applied in clinical practice. One or two eligible eyes from the same participant may be included in the study if all eligibility criteria are met.
Follow-up visits will be performed every 6 months for 2 years with a total of 5 visits. Participants will undergo the following assessments: multimodal retinal imaging, including OCT, OCTA, ultra-widefield (UWF) fundus fluorescein angiography (FFA) and fundus photography (FP), and color fundus photography (CFP); functional testing: best corrected visual acuity (BCVA) and microperimetry (Macular Integrity Assessment, MAIA); collection of systemic health variables, including glycated hemoglobin (HbA1c), blood pressure, diabetes duration, and relevant comorbidities. UWF-FFA assessments will be used to quantify both ischemic and leakage areas and to evaluate their longitudinal changes over time. Statistical analyses will account for repeated measurements and potential inter-eye correlation when both eyes from the same participant are included.
- Keywords
- Disease biomarkers
- Medical subject headings
- Diabetic Retinopathy, Diabetes Mellitus, Type 2, Diabetes Complications, Retinal Diseases
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Baseline to 24 months
Changes in retinal leakage area using UWF-FFA
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in retinal leakage area measured using ultra-widefield fluorescein angiography (UWF-FFA).
Measured: Baseline to Month 24
Secondary outcomes (5)
Changes in DRSS levels
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in DRSS classification, including one-step and two-step changes across DRSS levels using ultra-widefield fluorescein angiography (UWF-FFA).
Measured: Baseline to 24 months
Changes in Best Corrected Visual Acuity (BCVA)
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in BCVA, measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters.The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity.
Measured: Baseline to 24 months
Macular sensitivity using Microperimetry
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in average macular sensitivity (dB), fixation indices P1 and P2 (%), and Bivariate Contour Ellipse Area (BCEA; 63% and 95%) across DRSS levels.
Measured: Baseline to 24 months
Changes in Intraretinal Microvascular Abnormalities (IRMAs)
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in the presence and area of IRMAs using Swept-Source OCTA, UWF-FP and UWF-FFA.
Measured: Baseline to 24 months
Changes in neovascularization (NV)
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in the presence and area of NV using Swept-Source OCTA, UWF-FP and UWF-FFA.
Measured: Baseline to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start24 Nov 2025
- Primary completionNov 2027 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Association for Innovation and Biomedical Research on Light and Image
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação para a Ciência e a Tecnologia
- Responsible party
- Sponsor
- Investigators
- Inês P Marques, MD PhD, Principal investigator, AIBILI - Associação para a Investigação Biomédica e Inovação em Luz e Imagem
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07458516
- Sponsor's protocol ID
- 4C-2025-17
- Acronym
- IMPORTANT
- Status last verified
- Oct 2026
- First submitted
- 26 Feb 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 16750526Willis 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.
PubMed 28750122Whitehead 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.
PubMed 31485452