Determinants of severity and progression of diabetic retinopathy in Southern Malawi

Burgess, Philip
(2015) Determinants of severity and progression of diabetic retinopathy in Southern Malawi. Doctor of Philosophy thesis, University of Liverpool.

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Background Sub-Saharan Africa faces an epidemic of diabetes. The prevalence and incidence of sight threatening diabetic retinopathy in developed countries and associations between systemic factors, including glycaemic control, blood pressure and blood lipid levels, are well documented. In contrast the epidemiological literature from sub-Saharan Africa is sparse. In this resource-poor setting, population-specific variables such as a high burden of infectious disease and anaemia are likely to affect the spectrum of pathology encountered. I aimed to investigate the prevalence, incidence and progression of diabetic retinopathy in Southern Malawi, to investigate the risk factors for diabetic retinopathy severity and progression in this population and to characterise endothelial function in Southern Malawian subjects with diabetes. Methods I established the Malawi Diabetic Retinopathy Study, a 24 month prospective cohort study. Subjects were systematically sampled from two hospital-based, primary care diabetes clinics. Visual acuity, glycaemic control, systolic blood pressure, HIV status, urine albumin–creatinine ratio, and haemoglobin and serum lipid levels were assessed. Retinopathy was graded at an accredited reading centre using modified Wisconsin grading of four-field mydriatic photographs. Additionally, in order to investigate DR progression at five years, a cohort of subjects recruited to a cross-sectional study of diabetes complications in 2007 were traced and assessed. In a nested case-control study, serum markers of endothelial dysfunction and pulse amplitude tonometry were measured in a subset of subjects from the main cohort plus subjects without diabetes. Results 357 subjects were recruited to the 24 month cohort study. At baseline 13.4% subjects were HIV-positive and 15.1% were anaemic. Baseline prevalence rates of any retinopathy, sight threatening diabetic retinopathy and proliferative retinopathy were 50.1% (95% CI 44.9–55.3), 29.4% (95% CI 24.7–34.1) and 7.3% (95% CI 4.6–10.0), respectively. Cumulative incidence at 2 years of sight threatening diabetic retinopathy for subjects with level 10 (no retinopathy), level 20 (background) and level 30 at baseline was 2.7% (95% CI 0.1-5.3), 27.3% (16.4-38.2) and 25.0% (0-67.4), respectively. In a multivariate logistic analysis, 2 step progression of diabetic retinopathy at 2 years was associated with HbA1c (odds ratio 1.27, 95%CI 1.12-1.45), baseline grade of DR (1.39, 1.02-1.91) and HIV infection (OR 0.16, 0.03-0.78). At 2 years, rates of progression to visual loss were: ≥15 letters lost in 17 subjects (5.8%), moderate visual impairment (<60 letters) in 3 subjects (1.0%), severe visual impairment (<50 letters) in 5 subjects (1.7%). The five year incidence of sight threatening diabetic retinopathy in subjects recruited to the 2007 cross sectional study, for those with level 10 and level 20 retinopathy at baseline, was 19.4% (11.3-27.4) and 81.3% (62.1-100), respectively. In the case control study of endothelial function higher serum VEGF and E-selectin were associated with having diabetes in multivariate regression. Serum VCAM-1 was associated with death in multivariate regression. Conclusions I report the first cohort study of diabetic retinopathy from sub-Saharan Africa. I found a prevalence of sight threatening diabetic retinopathy, in subjects attending diabetes clinics, approximately 3 times that reported in recent European studies and a prevalence of proliferative retinopathy approximately 10 times higher. Progression to sight threatening diabetic retinopathy occurred approximately 3 times more frequently than reported in Europe. The negative association of HIV infection with retinopathy progression is a new finding. I report the first evidence from sub-Saharan Africa of endothelial dysfunction in subjects with diabetes and of an association between levels of endothelial biomarkers and mortality in these subjects. Results presented in this thesis highlight the urgent need for provision of services for retinopathy detection and management to avoid a large burden of vision loss.

Item Type: Thesis (Doctor of Philosophy)
Subjects: R Medicine > RE Ophthalmology
Divisions: Fac of Health & Life Sciences > The School of Tropical Medicine
Depositing User: Symplectic Admin
Date Deposited: 22 Aug 2016 07:41
Last Modified: 22 Aug 2016 07:41
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