Relationships between subtle ocular changes and microvascular complications in people with type 2 diabetes

Background: Developing treatments for early microvascular type 2 diabetes (T2DM) complications (retinopathy (DR), peripheral neuropathy (DPN), nephropathy (DN)) is limited by insufficient understanding of early pathologies. The eye, prone to diabetic damage, is a microvascular bed accessible for ocular imaging, which has developed rapidly over recent years. There is a need for integrated investigations employing new methods to examine changes across different ocular tissues in individuals with T2DM and microvascular complications. Aims: 1) To explore potential relationships between ocular markers in humans, in vivo. 2) To investigate whether these ocular markers vary between individuals without diabetes, individuals with T2DM and no complications (no DR, DPN, or DN), and patients with T2DM and complications. 3) To validate and where needed, develop analytical methods of quantifying retinal and choroidal biomarkers of structure and/or function, including novel biomarkers such as choroid thickness, choriocapillaris perfusion, and retinal capillary perfusion, to ensure collection of high-quality data for aims 1) and 2). Methods: 1) Methodology development: approaches of assessing novel ocular biomarkers were developed and validated with low inter-scan coefficients of variability (CV): retinal capillary perfusion markers within three vascular plexuses (1.09%-6.11% CV), choroidal thickness (CT; mean 2.87% CV), markers of choriocapillaris (CC) perfusion (3.48%-18.70% CV). Other ocular biomarkers (retinal vessel diameters and their ratio, retinal vessel oxygenation, thickness of retinal layers, and flicker induced vasodilation (FIV) were also utilised. 2) Clinical study: participants attending the research centre underwent ocular testing forming a pool of 342 participants with data available for this thesis, including 97 T2DM-free controls. Exclusion criteria were applied to some ocular tests (e.g. patients with glaucoma excluded from retinal thickness tests). Statistics: Correlations between ocular markers (Pearson/Spearman/partial) and differences between the three groups (ANOVA/Kruskal-Wallis/ANCOVA) were assessed. Multiple linear regression tests were used to investigate the relationship between a dependent variable and two or more independent variables. Results: The key findings from the clinical studies are summarised below: •Retinal capillary perfusion in all three retinal plexuses correlated with choriocapillaris perfusion in T2DM but not in individuals without diabetes. •Choriocapillaris and retinal capillary perfusion were reduced in T2DM, even in the complication-free T2DM group. •CT was negatively associated with DPN, thickness of retinal nerve fibre layer, and positively associated with the ganglion cell layer thickness in patients with T2DM (combined group of patients with and without microvascular complications). •CT was positively correlated with diameters of retinal vessels (indicating possible vessel dilation across multiple ocular vascular beds) and outer retinal thickness, but almost exclusively in participants with T2DM. •Presence of DR and DPN were associated with reduced thickness of the inner plexiform layer in patients with T2DM. •Reduced retinal oxygen uptake is associated with a presence of DR in patients with T2DM. •There is evidence for a positive relationship between capillary perfusion and innermost retinal layers thickness in patients with T2DM. •Reduced in FIV (relating to neurovascular coupling) was associated with retinal neurodegeneration, but not vascular markers, in T2DM. Conclusion: Together, these results indicate ocular pathologies in T2DM, even in the absence of complications. Diabetic ocular disease is not limited to retinal vasculature, but rather involves interlinked vascular and/or neural changes of the retina and choroid.<p></p>

Author dc:creator

• Natalia Rolinska (21038249)

• T2DM
• Diabetes
• Diabetic Retinopathy
• Diabetic Peripheral Neuropathy
• Diabetic Nephropathy
• Retinal Thickness
• Choroid Thickness
• Arteriole-to-Venule Ratio
• Retinal Microvasculature
• Retinal Perfusion
• Choriocapillaris Perfusion
• Optical Coherence Tomography Angiography
• Diabetic Microvascular Complications
• Retinal Oxygenation

Statement dc:rights

• All rights reserved

Identifier

10779/exe.31415492.v1

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oai:figshare.com:article/31415492