IMaging Pre-PrOlifeRative sTAge of Diabetic retiNopaThy to Guarantee Timely Treatment - IMPORTANT
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Changes in capillary skeletonized vessel density (SVD)
研究概览
简要总结
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.
详细描述
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.
The purpose of this observational, non-interventional, prospective, and longitudinal clinical study is to explore imaging, functional and systemic biomarkers of DR progression, in 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.
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
- •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.
结局指标
主要结局
Changes in capillary skeletonized vessel density (SVD)
时间窗: Baseline to 24 months
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.
Changes in capillary perfusion density (PD) using OCTA
时间窗: Baseline to 24 months
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.
Foveal Avascular Zone (FAZ) area
时间窗: Baseline to 24 months
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.
Foveal Avascular Zone (FAZ) perimeter
时间窗: Baseline to 24 months
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.
Foveal Avascular Zone (FAZ) circularity
时间窗: Baseline to 24 months
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.
Changes in retinal ischemic area using UWF FFA
时间窗: Baseline to 24 months
Evaluate baseline differences and longitudinal changes (from baseline to month 24) in retinal ischemic area (mm2) across DRSS levels.
Changes in central retinal thickness (CRT)
时间窗: Baseline to 24 months
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.
Changes in central intraretinal fluid
时间窗: Baseline to 24 months
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.
Changes in Disorganisation of Retinal Inner Layers (DRIL)
时间窗: Baseline to 24 months
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.
Changes in Disorganisation of Retinal Outer Layers (DROL)
时间窗: Baseline to 24 months
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.
Changes in Ganglion Cell Layer (GCL) + Inner Plexiform Layer (IPL) thickness
时间窗: Baseline to 24 months
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.
DRSS severity level
时间窗: Baseline to 24 months
Evaluate the DRSS score (range 10-85; higher scores indicate worse severity) in Ultra-widefield fundus photography (UWF-FP).
Changes in microaneurysm (MA) count
时间窗: Baseline to 24 months
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.
Changes in microaneurysm (MA) turnover
时间窗: Baseline to 24 months
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.
次要结局
- 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)