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Item Differences in Ocular Blood Flow Between People of African and European Descent With Healthy Eyes(Lippincott, Williams, and Wilkins, 2016-09) Kaskan, Betül; Ramezani, Koosha; Harris, Alon; Siesky, Brent; Olinde, Carine; WuDunn, Darrell; Eikenberry, Jennifer; Tobe, Leslie A.; Racette, Lyne; Department of Ophthalmology, IU School of MedicinePurpose: To investigate differences in ocular blood flow between people of African descent (AD) and European descent (ED) with healthy eyes. Materials and Methods: Retrobulbar and retinal capillary blood flow was assessed in 1 eye of 58 participants (24 AD, 34 ED) with healthy eyes with systemic blood pressure lower than 140/90. Retrobulbar blood flow was measured in the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA) and temporal posterior ciliary artery (TPCA). Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were assessed. Retinal capillary blood flow was assessed using mean retinal flow and avascular space defined as the percent of area measured with no blood flow. Groups were compared using t tests and Pearson correlations were compared using Fisher r-to-z transformation. Results: Compared with people of ED, people of AD had significantly lower EDV in the NPCA (P=0.01), and higher RI in the CRA (P=0.04) and TPCA (P=0.01). No significant differences were observed in mean retinal capillary flow or avascular area. In the CRA, a significant negative correlation was observed between pattern standard deviation and peak systolic velocity (P=0.02) in the AD group and this correlation was significantly different from that observed in the ED group (P=0.01). A significant correlation was also observed between pattern standard deviation and EDV (0.04) in the AD group. Conclusions: This study suggests that retrobulbar blood flow is lower in healthy eyes in persons of AD compared with ED. This may provide a mechanism through which people of AD are at increased risk for ophthalmic diseases such as glaucoma.Item Multiscale mathematical modeling of ocular blood flow and oxygenation and their relevance to glaucoma(2016-06-14) Carichino, Lucia; Guidoboni, Giovanna; Harris, Alon; Arciero, Julia ConcettaGlaucoma is a multifactorial ocular disease progressively leading to irreversible blindness. There is clear evidence of correlations between alterations in ocular hemodynamics and glaucoma; however, the mechanisms giving rise to these correlations are still elusive. The objective of this thesis is to develop mathematical models and methods to help elucidate these mechanisms. First, we develop a mathematical model that describes the deformation of ocular structures and ocular blood flow using a reduced-order fluid-structure interaction model. This model is used to investigate the relevance of mechanical and vascular factors in glaucoma. As a first step in expanding this model to higher dimensions, we propose a novel energy-based technique for coupling partial and ordinary differential equations in blood flow, using operator splitting. Next, we combine clinical data and model predictions to propose possible explanations for the increase in venous oxygen saturation in advanced glaucoma patients. We develop a computer-aided manipulation process of color Doppler images to extract novel waveform parameters to distinguish between healthy and glaucomatous individuals. The results obtained in this work suggest that: 1) the increase in resistance of the retinal microcirculation contributes to the influence of intraocular pressure on retinal hemodynamics; 2) the influence of cerebrospinal fluid pressure on retinal hemodynamics is mediated by associated changes in blood pressure; 3) the increase in venous oxygen saturation levels observed among advanced glaucoma patients depends on the value of the patients’ intraocular pressure; 4) the normalized distance between the ascending and descending limb of the ophthalmic artery velocity profile is significantly higher in glaucoma patients than in healthy individuals.Item Racial differences in correlations between optic nerve head morphology and ocular blood flow in healthy eyes(Office of the Vice Chancellor for Research, 2016-04-08) Ramezani, Koosha; Harris, Alon; Siesky, Brent A; Olinde, Carine; WuDunn, Darrell; Kaskan, Betül; Eikenberry, Jennifer; Tobe, Leslie A.; Racette, LynePurpose: To assess differences in the relationship between optic nerve head (ONH) morphology and ocular blood flow between persons of African descent (AD) and European descent (ED) with healthy eyes. Methods: 46 participants (20 AD, 26 ED) with normal fundoscopic exam and intraocular pressure were included. Each participant was assessed for disc area (DA), rim area (RA), linear cup to disc ratio (CDR), mean retinal nerve fiber layer (RNFL) thickness by Heidelberg retina tomograph. Retrobulbar blood flow was assessed by color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal short posterior ciliary (NPCA) and temporal short posterior ciliary (TPCA) arteries. Peak systolic velocity (PSV), end diastolic velocity (EDV) and the resistive index (RI) were assessed in each artery. Mean retinal capillary blood flow and % of the area with no blood flow in both hemifields were measured with Heidelberg retinal flowmeter. Correlations between ONH morphology and ocular blood flow were derived using Pearson correlations. Differences between the correlations in the AD and ED groups were assessed using the Fisher r-to-z transformation method. Results: Age, gender, IOP and blood pressure were not significantly different between groups. Significant differences in correlations were observed between groups in the CRA. In this artery, PSV and DA were positively correlated in AD (r=0.43) and negatively correlated in ED (r=-0.35) (Δr=0.78; p=0.01). A similar finding was observed for PSV and RA (AD: r=0.39; ED: r=-0.22; Δr=0.61; p=0.04). Significant negative correlations between RI and CDR were observed in all arteries in the ED group (r coefficients range=-0.48 to -0.39), but not in the AD group (r coefficients range=-0.14 to 0.17). No significant differences were observed in the correlations of ONH morphology and capillary blood flow. Conclusion: ONH morphology and ocular blood flow relationship was significantly different in the healthy eyes of AD compared to ED.Item Reductions in retrobulbar and retinal capillary blood flow strongly correlate with changes in optic nerve head and retinal morphology over four years in open-angle glaucoma patients of African descent compared to patients of European descent(Wolters Kluwer, 2016-09) Siesky, Brent; Harris, Alon; Carr, Joseph; Vercellin, Alice Verticchio; Hussain, Rehan; Hembree, Priyanka Parekh; Wentz, Scott; Isaacs, Michael; Eckert, George; Moore, Nicholas A.; Ophthalmology, School of MedicinePurpose To investigate the relationship of changes in ocular blood flow with optic nerve head and retinal morphology in open-angle glaucoma patients of African versus European descent over four years. Materials and Methods In this study, 112 patients with open-angle glaucoma were examined at baseline, 79 (59 European descent, 20 African descent) of which were followed for four years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured by color Doppler imaging. Retinal structural changes were examined with optical coherence tomography and Heidelberg retinal tomography-III. Mixed-model analysis of covariance was used to test for the significance of change from baseline to four-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations. Results In open-angle glaucoma patients of African descent, structural changes of the optic nerve head demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over four years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of African descent, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness. Conclusion Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the optic nerve head and macular thickness over four years in open-angle glaucoma patients of African descent compared to European descent. This data suggests that ocular vascular health may be a more influential contributing factor in the pathophysiology of open-angle glaucoma in patients of African descent compared to European descent.