Characterization of Retinal Vascular Disease in Eyes With Mild to Moderate NPDR in Diabetes Type 2
Condition: NPDR - Non Proliferative Diabetic Retinopathy
MeSH terms: Diabetic Retinopathy; Vascular Diseases; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      Characterization of Retinal vascular disease in eyes with mild to moderate NPDR in Diabetes
      type 2, using novel non-invasive Imaging methods, in a longitudinal, prospective and
      interventional clinical Study with 2 years of duration (CORDIS).
    

Detailed description: 
      Diabetic Retinopathy (DR) is a frequent complication of Diabetes Mellitus (DM) and is the
      main cause of vision loss in the working population in western countries.

      Several studies provided evidence that good diabetic control is important to prevent and
      delay disease progression, but while some patients develop sight-threatening DR (STDR)
      despite good control, others escape the development of vison loss with poor metabolic
      control.

      The STDR is defined as DME and PDR. DME is defined as thickening of the macula and is mainly
      due to accumulation of fluid in the central macular area resulting mainly from fluid leakage
      due to the alterations of the BRB. Identifying the eyes/patients at risk to develop central
      involved macular edema (CIME) and consequent vision-loss, as well as to understand its causes
      is fundamental for its appropriate treatment and, finally, to avoid vision loss due to DME.

      Several studies have shown different prevalence's of DR, ranging from 10.1% to 48.1%.

      The prevalence of DM in Portugal has increased and, between patients aged 20 to 79 years, was
      11.7% in 2009, reaching 13.3% in 2013.

      Chronic diseases often begin with a symptom-free phase being biomarkers fundamental in the
      identification of high-risk individuals in a reliably and timely manner, so that they can
      either be treated before onset of the disease or as soon as possible.

      Our group has identified 3 different phenotypes of progression based on the microaneurysm
      (MA) turnover rate (sum of MA formation and disappearance rates) and central retinal
      thickness (RT) measurements obtained using non-invasive repeatable procedures: digital color
      fundus photography (CFP) and optical coherence tomography (OCT). MA turnover can identify
      eyes at risk of progression to Clinically Significant Macular Edema (CSME), as shown by our
      research results and an independent group. RT obtained with OCT provides insight into
      morphological changes of the retina in DR and DME, allowing the detection of retinal edema.

      The current study will address only two of the published phenotypes, B and C, which show more
      rapid progression to STDR.

      For an improved characterization of the main microvascular alterations that occur in NPDR,
      the investigators will use novel noninvasive, direct, objective and quantitative OCT-based
      methodologies: Optical coherence tomography angiography (OCTA) and OCT-Leakage (OCT-L).

      OCTA allows the construction of three-dimensional blood flow information, and therefore can
      serve as a method to evaluate ocular circulation. OCTA is non-invasive and has the potential
      to be superior to fluorescein angiography (FA) in the detection and follow-up of DR lesions
      and mean vessel density measured in the superficial retinal layer in OCTA revealed to be a
      good differentiator between healthy eyes and eyes with DR. Vessel density was also correlated
      with best corrected visual acuity (BCVA) and severity of DR, suggesting that capillary
      closure may provide relevant information regarding progression of DR in individual patients
      with DM and may be a potential indicator for vision loss.

      OCT-Leakage (OCT-L) is a new non-invasive imaging technique that performs automated analysis
      of the retinal extracellular space using spectral-domain optical coherence tomography
      (SD-OCT). Abnormal fluid accumulation is an indicator of breakdown of the blood-retinal
      barrier (BRB), which is an early and frequent finding in DR. Our research group showed the
      importance of this new method and demonstrated the increased sensitivity of OCT-L to detect
      abnormal fluid in the retina when compared with FA. This can be particularly useful to better
      characterize and identify features associated to leaky phenotype B.

      A major objective of this study is to investigate changes in OCTA and OCT-L that may be
      biomarkers in the diagnosis and progression of NPDR and its ability to distinguish different
      stages of the disease. The identification with OCT-L of the abnormal fluid and alteration of
      the blood-retinal barrier (BRB), its location and quantification, complementing conventional
      OCTA, providing, therefore, information on capillary closure, vascular morphology and their
      alterations over 2 years, are expected to contribute to our understanding of DR progression.

      Validation of biomarkers of DR progression, such as MA turnover and RT are important steps.
      However, OCTA and OCT-L offer an opportunity of improved characterization of the different DR
      phenotypes.

      This study intends to better characterize the main alterations of the different phenotypes of
      DR considered to be leaky (OCT-L) or ischemic (OCTA), and to identify patients at risk of
      progression to STDR, identified in this study as central-involved ME (CIME), objectively
      measured by OCT or development of PDR, using these recent non-invasive techniques: OCTA and
      OCT-L.
    

Intervention name(s): Laboratory tests
Intervention type(s): Diagnostic Test
Intervention description(s): • Laboratory tests (HbA1C levels and lipids)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other