Adams, Edward James Alfred; (2025) Impact of Diabetic Eye Disease on Choroidal Vasculopathy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Diabetic eye disease includes various conditions such as diabetic retinopathy (DR), diabetic macular edema (DME), and diabetic choroidopathy that are major causes of visual impairment. Increasing evidence suggests that diabetic alterations in the choroid and choriocapillaris (CC) contribute to early outer retinal dysfunction. This thesis presents a comprehensive investigation into the struc- tural and physiological consequences of diabetic alterations, emphasising novel methodological de- velopments in imaging analysis, vascular flow modelling, and oxygen diffusion simulation. Advanced image processing techniques were developed to quantify CC flow voids using swept-source optical coherence tomography angiography (SS-OCTA). Morphological metrics and statistical analysis were used to characterise flow voids in diabetic eyes. Flow voids were significantly elevated compared to controls and were statistically associated with reduced ellipsoid zone (EZ) reflectivity. Three- dimensional (3D) vascular models of the choroid and CC were constructed from micro-CT imaging, confocal microscopy, and synthetically generated. These models were anatomically informed by our OCTA analysis of flow voids and were used to simulate blood flow, revealing localised increases in flow and heterogeneous redistribution of flow at CC drop-out boundaries, supporting a mechanistic link between structural changes and flow. To assess the impact on retinal oxygenation, a Green’s function-based model of oxygen diffusion was implemented. This approach, adapted for elliptical CC geometry, demonstrated that CC drop-out leads to significant localised hypoxia. This thesis introduces and integrates new tools for quantifying CC disruption and simulating its physiological consequences. These findings support the role of CC pathology in diabetic eye disease and lay the groundwork for future diagnostics and targeted therapies focused on preserving outer retinal function.

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