Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04650165 |
| Other study ID # |
CEC/011/20 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2021 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Association for Innovation and Biomedical Research on Light and Image |
| Contact |
Inês P Marques, MD |
| Phone |
+351239480127 |
| Email |
ipmarques[@]aibili.pt |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
To characterize both functionally and morphologically initial Diabetic Retinopathy (DR)
stages and their progression over a period of 10 years.
Description:
Diabetic retinopathy (DR) is the most frequent complication of diabetes mellitus and the
leading cause of legal blindness in active populations of industrialized countries.
Progression of DR has been up to now classified according to the ETDRS classification, based
on a multicentric study that evaluated the effect of laser photocoagulation on advanced
stages of DR. Although appropriate for late stages of DR, it does not grade progression well
in the initial stages of the disease. Initial stages of DR require urgent characterization
and their evolution should be well defined because some of the lesions are still reversible.
The early stages of DR are characterized by 4 main alterations: microaneurysms (MA) and
retinal hemorrhages, represented by red dots in the fundus, blood-retinal barrier breakdown,
capillary closure and damage of neuronal and glial cells of the retina. Thus, there are both
microvascular changes, with endothelial cell and pericyte damage with thickening of basement
membrane, and neuronal changes.
Based on previous studies, progression of DR does not occur at the same rate in all patients.
Some never develop vision loss, whereas others rapidly progress to macular edema or
neovascularization leading to vision loss. The understanding of the mechanisms that balance
in different direction is of outmost importance. The duration of diabetes mellitus and the
metabolic control are major risk factors for DR progression, but they are insufficient to
explain the great variability observed in patients.
Recent data indicate that MA turnover may be an appropriate indicator of DR progression. Our
research group has identified different DR progression phenotypes. Phenotype A is
characterized by a low MA turnover, phenotype B characterized by increased thickness and
phenotype C with predominant ischemia, with a high MA turnover. These phenotypes were defined
based on MA turnover (RetmarkerDR) and on central retinal thickness (RT) measured by Optical
Coherence Tomography (OCT) and the model was able to correctly identify eyes at risk of
progression. 61,8-76,7% of eyes with an increase RT in the central subfield, inner and/or
outer ring allowed a MA formation rate ≥ 2 and/or a MA turnover ≥ 6. More recently, some
genetic variants have been linked to the different phenotypes and may explain specific
progression patterns.
There is emerging evidence to suggest that retinal neurodegeneration is an early event in the
pathogenesis of DR and that it could participate in the development of microvascular
abnormalities. The understanding of the underlying mechanisms leading to neurodegeneration
and the identification of the mediators between neurodegeneration and microangiopathy is
essential.
The Investigators aim to understand the extent of these cell abnormalities in the initial
stages of DR and to characterize their progression.
Analysis of retinal thickness using OCT offers non-invasive evaluation of retinal edema and
can suggest an appropriate treatment target. The Investigators will use recent and innovative
approaches as Spectral domain OCT (SD-OCT) with retinal layers segmentation to study
neurodegenerative changes occurring in DR. OCT-Angiography and OCT-Leakage layer by layer
analysis will be used for microvasculature and blood retinal barrier assessment.
