M.Phil. (Optometry) / Despite many years of research, diabetic retinopathy (DR), and diabetic macular edema (DME) remain difficult to diagnose, prevent, and treat. The complicated nature of the disease, the limited information on DR and DME and the increasing prevalence of diabetes mellitus (DM) in South Africa, provided motivation for this study. To the best of my knowledge, this is the first study in our country to identify demographic, medical and visual aspects ofDR and DME collectively. A further incentive was the availability in optometry of recently developed computer software based upon multivariate statistics, which provided a unique opportunity to analyze, for example, tri-variate contrast sensitivity acuities using stereo-pair scatter plots. All refractive status measurements were also analyzed and compared with the same method. Together, the results from this study provide a broader clinical and research perceptive on DR and DME. In this cross-sectional study, 202 diabetic patients at the Helen Joseph Hospital in Johannesburg were recruited. Demographic variables included age, gender, race, age of diagnosis, duration of DM, and social habits. Medical variables included systemic conditions present, blood pressures, body mass index (BMI), lipid profiles, glycerated haemoglobin (HbAlc), and other available biochemical data (for example cholesterol, urea and creatinine levels). Visual variables included, distance, pinhole and near visual acuities, contrast sensitivity acuities, refractive status measured with autorefraction, colour vision, Amsler grid, intraocular pressures (lOP), and fundus photography. Administration of the Impact of Visuallmpainnent (IVI) questionnaire provided new information concerning the restrictions in daily living participation caused by DR or DME. The predominant characteristics of the study population consisted of Type 1DM among female Coloured subjects. Approximately 66% of all subjects had also been diagnosed with hypertension. The mean age ofthe subjects was 52 (± 14) years, age of diagnosis 41 (± 13) years, and duration ofDM 10.8 (± 9.7) years. Mean blood pressures (136/81 ± 20.5/11 mmHg) and glycated haemoglobin (HbAlc, 9.9 ± 3.4%) values were slightly higher than the recommended control levels (BP= 120/80 mmHg and HbAlc = 6 to 7%).

Indiana University-Purdue University Indianapolis (IUPUI) / Transforming growth factor β-activated kinase 1 (TAK1), a hub kinase at the convergence of multiple signaling pathways, is critical to the development of the central nervous system and has been found to play a role in cell death and apoptosis. TAK1 may have the potential to elucidate mechanisms of cell cycle and neurodegeneration. The Belecky-Adams laboratory has aimed to study TAK1 and its potential roles in cell cycle by studying its role in chick retinal development as well as its possible implication in the progression of diabetic retinopathy (DR). Chapter 3 includes studies that explore TAK1 in a study in chick retinal development and TAK1 in in vitro studies in retinal microglia. Using the embryonic chick, immunohistochemistry for the activated form of TAK1 (pTAK1) showed localization of pTAK1 in differentiated and progenitor cells of the retina. Using an inhibitor or TAK1 activite, (5Z)-7-Oxozeaenol, in chick eye development showed an increase in progenitor cells and a decrease in differentiated cells. This study in chick suggests TAK1 may be a critical player in the regulation of the cell cycle during retinal development. Results from experimentation in chick led to studying the potential role of TAK1 in inflammation and neurodegeneration. TAK1 has previously been implicated in cell death and apoptosis suggesting that TAK1 may be a critical player in inflammatory pathways. TAK1 has been implicated in the regulation of inflammatory factors in different parts of the CNS but has not yet been studied specifically in retina or in specific retinal cells. Chapter 2 includes studies from the Belecky-Adams laboratory of in vitro work with retinal microglia. Retinal microglia were treated with activators and the translocation to the nucleus of a downstream factor of TAK1 was determined: NF-kB. Treatment of retinal microglia in the presence of activators with TAKinib, an inhibitor of TAK1 activation, revealed that TAK1 inhibition reduces the activation of downstream NF-kB. Together this data suggests that TAK1 may be implicated in various systems of the body and further studies on its mechanisms may help elucidate potential therapeutic roles of the kinase.

PURPOSE: Previous studies have reported an increased prevalence of ocular diseases in patients with obstructive sleep apnea. The purpose of this study was to examine the link between such ocular diseases as diabetic retinopathy, diabetic macular edema, retinal vein occlusion, central serous chorioretinopathy, age-related macular degeneration, non-arteritic anterior ischemic optic neuropathy, and glaucoma. METHODS: This meta-analysis was conducted through a search using PubMed, Web of Science, Scopus and EMBASE. We identified both retrospective and prospective studies. RESULTS: The final meta-analysis looked at 30 studies and 7 ocular diseases. The data showed a high prevalence of obstructive sleep apnea for diabetic retinopathy and diabetic macular edema patients. Data for glaucoma and non-arteritic anterior ischemic optic neuropathy patients did not show a statistical increase. There was not enough data for retinal vein occlusion, central serous chorioretinopathy and age-related macular degeneration to calculate statistical significance. CONCLUSION: These data suggests that patient populations with diabetic retinopathy and macular edema show increased rates of obstructive sleep apnea. Data suggest that hypoxia is an important part of the pathophysiology of diabetic retinopathy and diabetic macular edema. Because obstructive sleep apnea has been shown to affect the progression of the ocular diseases included in this study, ophthalmologists should screen for the presence of obstructive sleep apnea to better help their patients. / 2021-06-14T00:00:00Z

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Diabetic retinopathy (DR) is an incurable, chronic disease that is the leading cause of blindness in working-age adults. A prominent characteristic of DR is the extensive dysfunction within the retina microvasculature. Specialized vascular cells known as pericytes (PCs) are lost or become dysfunctional during disease progression; a thickening of the extracellular matrix (ECM) composing the vascular basement membrane (vBM) and endothelial cell (EC) tight junction disruption are also key features of this disease and contribute to its pathogenesis. PC loss is believed to be a central cue for disease initiation. However, studies inducing PC loss and observing acute changes in the vasculature did not report severe vessel damage or vBM thickening, suggesting that the effects of PC loss occur over a longer period of time. Because the chronic effects of PC loss are more difficult to ascertain, especially in a complex condition such as DR, the mechanisms underlying microvascular defects in DR remain poorly understood. The work presented in this dissertation focuses on pericyte-endothelial cell interactions and their interplay with the ECM/vBM during a variety of physiological and pathological conditions. First, we isolated and functionally validated a primary mouse embryonic PC cell line that we then applied to a co-culture model with ECs to better understand the dynamic interactions between these two critical components of the capillary wall. In the co-culture model, we found that primary PCs promoted EC organization into vessel-like structures and enhanced EC-EC junctions. To complement these in vitro studies, we analyzed animal models and human tissue for the PC-EC interactions and ECM/vBM remodeling under different conditions (physiological and pathological). Moreover, we analyzed microglia and astrocytes to enhance our understanding of the tissue-vessel interface, bolstering our experimental results and facilitating the generation of more hypotheses for future research. Overall, our work suggests that PC-EC interactions in diabetic scenarios play a crucial role in ECM/vBM remodeling; engagement with the ECM/vBM in turn impacted PC behaviors including migration away from the endothelium and induced EC loss of tight junctions, key changes in the onset and progression of DR. / Doctor of Philosophy / Diabetic retinopathy is a group of eye diseases occurring in patients suffering from diabetes and is the leading cause of adult blindness among the working-aged. About one in three people with diabetes over the age of 40 have overt signs of DR. The primary cause for this disease is long-term, high blood sugar levels that damages blood vessels systemically as well as in the eye. Current treatments for DR can prevent the condition from getting worse, but no treatment exists that results in a complete cure. This work described in this dissertation focuses on the interactions between vascular pericytes and endothelial cells, two of the main cell types that compose capillaries (i.e. the smallest blood vessels important for oxygen delivery). The studies presented herein also focus on the response of these cells to the extracellular matrix, a scaffold of proteins that surround pericytes and endothelial cells to stabilize blood vessels. We found that extracellular matrix components dramatically increase as a result of the interactions between pericytes and endothelial cells exposed to diabetic conditions. These changes in the extracellular matrix also had important effects on pericytes and endothelial cells and their engagement with their environment and other cells. Taken together, our work suggests that pericyte-endothelial cell interactions and their crosstalk with the ECM play an important role in blood vessel formation and in the accumulation of microvascular defects that fuel diabetic retinopathy progression.

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1571. Adviser: Craig L. Hanis. Includes bibliographical references.

Magister Public Health - MPH / BACKGROUND AND RATIONALE: The Cape Town Metro District Health Service (MDHS) has introduced a Diabetic RetinopathyScreening (DRS) programme incorporating retinal fundal photography in diabetic services at primary health care (PHC) facilities. Hitherto, coverage of the DRS programme has been less than optimal in part due to volumes of diabetic patients attending PHC facilities. The aim of this study was to identify possible sub-groups of patients, attending the Cape Town DRS Programme, who are at most risk of diabetic retinopathy and might be prioritised for early diabetic retinopathy detection and subsequent sight-saving treatment. METHODOLOGY: A case-control study of risk factors for treatment-requiring diabetic retinopathy was conducted. This research sampled participants from the DRS programme provided by the MDHS eye care team to Type II diabetics attending public PHC facilities within the Klipfontein and Mitchells Plain Sub-Districts. Based on fundal images, cases were selected as those requiring ophthalmological treatment; and controls (three matched per case by area of residence) as those judged as not requiring ophthalmological treatment for diabetic retinopathy. Data on possible risk factors (clinical, laboratory) were extracted from the patients' folders. RESULT: The study included 453 participants, of whom 113 (24.9%) were cases and 340 (75.1%) were controls. Three factors were significantly associated with treatment-requiring diabetic retinopathy on multivariate analysis: Insulin dependency (OR of 2.96, 95% CI: 1.75 – 5.00); duration of diabetes of more than 10 years (OR of 3.44, 95% CI: 2.06 – 5.74) and sustained hyperglycaemia over the past six months (OR of 3.73, 95% CI: 1.69 – 8.22). A screening algorithm combining these criteria had a sensitivity of 61.2% (95% CI: 51.9 – 70.5). CONCLUSION: The findings indicate that a sub-set of patients attending the DRS programme in the Klipfontein and Mitchells Plain Sub-Districts have a greater likelihood of presenting with treatment-requiring diabetic retinopathy. Further research is required to develop a tool that is sufficiently sensitive to safely prioritise patients for fundal screening. / National Research Foundation (NRF)

Thesis (MPH.) -- University of Limpopo, 2021 / Background: Diabetes mellitus (DM) is a major public health problem, and it remains one of the global epidemics of non-communicable diseases. Diabetic retinopathy (DR) is a micro-vascular complication of DM due to a prolonged hyperglycaemia, and it is the most common cause of a visual loss in people living with DM. The global increase in the prevalence of DM has led to an increase in prevalence of diabetic complications, such as DR. The primary aim of this study was to investigate the prevalence and determinants of DR among the DM patients receiving treatment from Maruleng public healthcare facilities, Mopani District in the Limpopo Province. Methodology: A quantitative cross-sectional survey was used as a primary source data from the DM patients who were readily available at the selected public healthcare facilities to collect a chronic treatment during the time of the study. Selection of eligible DM patients was done through a convenient sampling technique for those who were readily available or willing to take part of the study after receiving all information about the study for them to consent freely without any form of coercion by researcher or any other person. All selected respondents had undergone face-to-face interviews and basic clinical screening for DR to collect a primary source data using piloted structured researcher-administered questionnaire to record data collected from respondents, and calibrated medical equipment were used to measure a clinical variables during clinical screening. Data analysis was carried out using Statistics and Data Analysis (STATA) version 15 software for windows. The characteristics of DM patients were summarised and analysed using a descriptive statistics. Inferential statistics were performed on dependent variable and independent variables using a logistic regression analysis to determine the strength of association between variables, where a potential predictors of DR among DM patients were identified at significant level of less than 0.05 (p<0.05). Results: Out of the 416 DM patients who participated in the study, the majority were females (n=315; 76%) and all DM patients were above the age of 18 years, with a mean age of 61 years (standard deviation [SD] =11.5). The overall prevalence of DR was 35.4% comprising 32% mild non-proliferative DR (NPDR) and 3.4% moderate NPDR. DR was found to be slightly more prevalent in females, at 35.9%, than in males, at 34.6%; particularly in those females with type 2 DM, at 35.1%, comprising 32.1% mild NPDR and 3% moderate NPDR. DR was more prevalent in older females, at 77.8%, comprising 55.6% mild NPDR and 22.2% moderate NPDR. The DM patients aged 55 years and above were found to be 2.7 times more likely to develop DR, at p<0.001, and DM patients with higher systolic blood pressure of 140 mmHg or more were found to be 1.4 times more likely to develop DR as compared to DM patients with a systolic blood pressure of 139 mmHg or less (≤139 mmHg), at p<0.05. Employed DM patients were 1.4 times more likely to develop DR as compared to unemployed DM patients, at p<0.001. Age of the DM patients, high systolic blood pressure (SBP) or a hypertension of 140 mmHg or more (≥ 140 mmHg), and employment status were significantly associated with higher risk of developing DR among DM patients. Gender, hyperglycaemic state, poor glycaemic control, smoking and high BMI were found to be associated with DR but this association was not statistically significant. Conclusion and recommendations: Slightly more than one third of the DM patients receiving treatment during the study period from the public healthcare facilities in the Maruleng sub-district had some form of DR, which means that nearly four in ten DM patients had some form of DR. Diabetic retinopathy was more prevalent in females, and in older DM patients. Age of the DM patient, employment status, and high systolic blood pressure were significantly associated with an increased risk of developing DR among the DM patients. There is an urgent need to implement a health promotional programmes to educate people about the complications of a diabetes mellitus such as DR, and also to establish a coordinated screening programme for DR among DM patients receiving a chronic treatment, which must be supported by the Department of Health in all public healthcare facilities. Keywords: Diabetes Mellitus, Diabetic Retinopathy, Prevalence, Determinants / Health and Welfare Sector Education and Training Authority (HWSETA)

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