Early Retinal Neurodegeneration As Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age40-80
SponsorIRCCS Ospedale San Raffaele
About this trial
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).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Participant is willing and able to give informed consent for participation in the trial.
Male or Female, aged 40 - 80 years;
In good general health as evidenced by medical history or diagnosed with type 2 diabetes for less than 10 years without clinical signs of retinopathy and other diabetic complications;
HbA1c level 7% or greater;
Disqualifiers
retinal or systemic diseases other than diabetes;
hypertension (BP values greater than 140/90 mm Hg);
anemia (hematocrit less than 35%);
smoking;
Trial population
The longitudinal study will include 90 individuals affected by type 2 diabetes and 30 healthy controls. The cross-sectional study will include 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 (matched for age, gender and duration of diabetes) affected by type 2 diabetes with a duration of disease longer than 20 years and DR of any stage (in absence of laser treatment).
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Ophthalmological examination including imaging assessments
Procedure/SurgeryOphthalmological examination including imaging assessments (SD-OCT, Spectral Domain Optical Coherence Tomography, a procedure to study and quantify possible retinal neurodegeneration and OCT-A, Optical coherence tomography angiography, a procedure to study and quantify possible retinal vascular abnormalities)
confocal analysis of cornea
Procedure/SurgeryConfocal analysis of cornea: a procedure to study and quantify possible corneal nerve degeneration as a marker of involvement of diabetic neuropathy
Dynamic Vessel Analyzer (DVA)
Procedure/SurgeryDynamic Vessel Analyzer (DVA), a device that measures the response of retinal arteries and veins to a standardized stimulus (flickering light) allowing direct quantification of the inflammatory status of the retinal vasculature
tear sampling collection
Procedure/SurgeryCollect and analyze tear samples to identify biomarkers in tears and at the endothelium of the ocular surface through impression conjunctival cytology and the quantitative/qualitative analysis of pro-inflammatory cytokines
blood sampling collection
Procedure/Surgerycollection and analysis of blood samples to identify diabetic retinopathy biomarkers and early abnormalities of the vascular retinal system.
Treatment groups
180 Participants
are divided into 4 treatment groupsGroup A: cohort 1 (longitudinal study)5 interventions
Group B: cohort 2 (longitudinal study)5 interventions
Group C: cohort 1 (cross sectional study)5 interventions
Group D: cohort 2 (cross sectional study)5 interventions
Trial outcomes
Primary outcomes
1
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
* 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.
Time frame
24 monthsSecondary outcomes
1
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
* 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.
Time frame
24 monthsSponsors and contacts
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Source ClinicalTrials.gov