Early Retinal Neurodegeneration As Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy
- Conditions
- Diabetic RetinopathyDiabetic Retinopathy Associated with Type 2 Diabetes Mellitus
- Registration Number
- NCT06582472
- Lead Sponsor
- IRCCS Ospedale San Raffaele
- Brief Summary
Despite the evidence that diabetic retinopathy (DR) remains the first cause of blindness among the working-age population, it lacks a specific preventive treatment. This is because early mechanisms leading to the development of DR have been, until recently, unknown. Recent studies have suggested that the early stages of DR could be preceded by neuronal abnormalities, in particular retinal ganglion cell death, coupled with widespread retinal inflammation. According to these studies, endothelial dysfunction and the development of microaneurysms, the classic hallmarks of DR, could be the consequence of these early abnormalities.
This project will aim to verify whether neurodegeneration could represent at the same time: 1) a risk factor for subsequent development of DR (this will be investigated through a follow-up study in type 2 diabetic patients free of diabetic retinopathy). 2) a biomarker of the complication (if so, patients with long-standing diabetes in the absence of retinopathy should show no signs of neurodegeneration).
- Detailed Description
The project is centered on a clinical study aimed to clarify whether early, diabetes-driven neurodegeneration (something that has been demonstrated by several seminal studies) is related (possibly causative) to the subsequent development of DR (a concept that is presently far from being confirmed but that, in case, would probably pave the way to identify for the first time a treatment for this diabetic complication.
This project includes two substudies:
* LONGITUDINAL STUDY: the aim is to verify whether the presence of retinal neurodegeneration in type 2 diabetic patients without DR increases the risk of subsequent development of retinal microaneurisms, the classic first vascular sign of DR; will enroll 90 individuals affected by type 2 diabetes and 30 healthy controls. All the subjects will be recruited during the first 6 months of the study and followed for 24 months (baseline, month 6, month 12, month 18, and month 24).
* CROSS-SECTIONAL STUDY: the aim is to verify the clinical evidence of retinal neurodegeneration in patients with type 2 diabetes diagnosed over 20 years and with overt diabetic retinopathy, compared to patients with type 2 diabetes diagnosed for over 20 years but no signs of diabetic retinopathy. Will be enrolled 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and no clinical signs of DR and 30 individuals affected by type 2 diabetes with a duration of disease longer than 20 years and DR of any stage. All the subjects will be recruited during the first 6 months of the study and subjected to only one visit to the site.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology 24 months * Evaluation of changes in neuroretinal morphology by OCT (Optical coherence tomography), in the morphology of the retinal vascular component by OCT-A, and retinal blood perfusion due to the presence/absence of a light signal by Dynamic Vessel Analyzer);
* identification of retinal neurodegeneration factors as possible biomarkers of diabetic retinopathy, using conjunctival impression cytology and quantum/qualitative analysis of pro-inflammatory cytokines in tears and plasma;
* assessment of the appearance of signs of corneal nerve degeneration by confocal microscopy in patients with signs of overt retinal neurodegeneration.
- Secondary Outcome Measures
Name Time Method imaging assessment (OCT, Optical coherence tomography; OCT-A, Optical Coherence Tomography Angiography and Dynamic Vessel Analyzer); confocal microscopy, blood sampling collection and conjunctival impression cytology 24 months * Evaluation of changes in neuroretinal morphology by OCT (Optical coherence tomography), in the morphology of the retinal vascular component by OCT-A, and retinal blood perfusion due to the presence/absence of a light signal by Dynamic Vessel Analyzer);
* identification of retinal neurodegeneration factors as possible biomarkers of diabetic retinopathy, using conjunctival impression cytology and quantum/qualitative analysis of pro-inflammatory cytokines in tears and plasma;
* assessment of the appearance of signs of corneal nerve degeneration by confocal microscopy in patients with signs of overt retinal neurodegeneration.