Epidemiological and molecular risk factors for diabetic retinopathy blindness.

Author: Georgia Kaidonis

Kaidonis, Georgia, 2017 Epidemiological and molecular risk factors for diabetic retinopathy blindness., Flinders University, School of Medicine

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Abstract

A recent report suggests that 3.63 million people worldwide suffer from moderate and severe vision loss due to diabetic retinopathy (DR) and its related sequelae. Diabetic macular oedema (DMO), a subtype of DR, is responsible for greater visual morbidity than other vision threatening ocular diseases, and incurs significantly higher health care costs than other DR subtypes. Despite an expansion in research and knowledge regarding risk factors that predispose to the development of DR, many questions remain unanswered for a particularly susceptible subset of patients. It is clear that patients belonging to some ethnic groups have a propensity to develop DR and this requires further investigation. Furthermore, specific risk factors for the development of DMO are less well characterised compared with other forms of DR and genetic risk factors for DMO have largely been ignored. This PhD tries to answer some of these questions by targeting two specific areas that are currently poorly understood: (1) the epidemiology of DR and DR related visual loss in Indigenous Australians; and (2) the molecular risk factors associated with the development of DMO. A number of key findings from this PhD will contribute to reducing the burden of DR and DMO associated visual morbidity and health care costs in both Indigenous and non-Indigenous populations of Australia. The outcomes determined from the first population-based study of end-stage DR requiring vitrectomy has yielded valuable information regarding progression to vitrectomy and visual outcomes in Indigenous and non-Indigenous Australian populations. This information has guided the first Ophthalmic clinical trial in Central Australia designed as a part of this thesis and will continue to impact future initiatives aimed at improving visual outcomes in Indigenous Australians with DM. The exploration of candidate genes hypothesized to play a role in the pathogenesis of DMO in this robust genetic study has contributed to our current understanding of DMO susceptibility. The close interaction between inflammatory and angiogenic pathways in response to hypoxia is supported by our findings. Significant novel variants found within VEGFC and miR-146a validate the development of new therapeutic drugs targeting these pathways. Future evaluation of VEGFA variants and their interaction with environmental factors may help distinguish non-responders to current intravitreal treatments and assist clinicians employ individualized treatment strategies. The implication of our findings during an era of rapidly increasing incidence of T2DM and therefore DMO on vision related quality of life and health care costs are particularly noteworthy. The outcomes presented in this thesis are part of an ongoing research initiative that will continue to contribute to improving understanding and treatment of this global sight-threatening epidemic.

Keywords: Diabetes, diabetic retinopathy, diabetic macular oedema, blindness, vitrectomy, genetics, Indigenous Australians.
Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2017
School: School of Medicine
Supervisor: Prof. Jamie E Craig