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Title: The pathophysiology of diabetic macular oedema : a clinicopathological assessment
Author: Patel, Jignesh I.
ISNI:       0000 0004 2672 4293
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2008
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Diabetic macular oedema (DMO) is a devastating vision-threatening complication of diabetes mellitus. The broad aim of the thesis is to investigate the hypothesis that vitreomacular traction and growth factors are important contributors to the development of DMO. The contribution of vitreomacular traction was evaluated on the macular structural indices (foveal thickness and macular volume by Optical Coherence Tomography) and on functional effects (best corrected visual acuity) after 3-port pars plana vitrectomy (PPV) as part of clinical pilot studies with and without internal limiting membrane peels studies. The evaluation of growth factors in the vitreous, which was obtained at pars plana vitrectomy was performed using ELISA methods,. These vitreous samples from macular oedema patients (clinically graded as nonproliferative diabetic retinopathy NPDR) were compared to patients with full thickness macular holes (FTMH) and proliferative diabetic retinopathy (PDR). Lastly, using an immortalised rat retinal endothelial cell line, the effect of VEGF was explored to determine the molecular change at the junctional level. In the non-randomised pilot series of PPV, there was a significant improvement in the structural and functional indices at 12 months compared to baseline (p=0.037, p=0.01 respectively). However, in the pilot randomised and nonrandomised study including ILM peel, surgery provided little visual improvement despite structural benefit. These clinical studies of pars plana vitrectomy do suggest a role of vitreomacular traction in the development of macular oedema. Vitreal VEGF-A and HGF (angiogenic) concentrations were increased with a corresponding decrease in the angiostatic agents (soluble Flt-1 R antibody and PEDF). There were also changes in the angiopoietin 1 and 2 concentrations with significantly lower concentrations of angiopoietin 1 in macular oedema, suggesting a lower anti-permeability protective effect of angiopoietin 1. Haemodynamic (endothelin-1) and inflammatory (II-1 P) markers in the patients with macular oedema also demonstrated changes compared to control patients especially in endothelin-1 where there was a significant decrease in its concentration in the diabetic macular oedema. The effect of VEGF on cultured immortalised retinal endothelial cells (with primary rat endothelial culture acting as a comparison) did demonstrate that high concentrations of VEGF (100 ng/ml) could disrupt the organisation of tight junctions. These results demonstrate that the development of diabetic macular oedema is multifactorial with a range of physical (vitreomacular) and biochemical (cytokine) forces acting on and within the retina to produce leakage of fluid into the macula.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available