Dataset Information

Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent.

ABSTRACT: PURPOSE:To investigate the relationship of changes in ocular blood flow with optic nerve head (ONH) and retinal morphology in open-angle glaucoma (OAG) patients of African versus European descent (ED) over 4 years. MATERIALS AND METHODS:In this study, 112 patients with OAG were examined at baseline, 79 [59 ED, 20 African descent (AD)] of which were followed for 4 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 4-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations. RESULTS:In OAG patients of AD, structural changes of the ONH demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over 4 years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of AD, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness. CONCLUSIONS:Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the ONH and macular thickness over 4 years in OAG patients of AD compared with ED. These data suggest that ocular vascular health may be a more influential contributing factor in the pathophysiology of OAG in patients of AD compared with ED.

SUBMITTER: Siesky B

PROVIDER: S-EPMC5000863 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent.

Siesky Brent B Harris Alon A Carr Joseph J Verticchio Vercellin Alice A Hussain Rehan M RM Parekh Hembree Priyanka P Wentz Scott S Isaacs Michael M Eckert George G Moore Nicholas A NA

Journal of glaucoma 20160901 9

<h4>Purpose</h4>To investigate the relationship of changes in ocular blood flow with optic nerve head (ONH) and retinal morphology in open-angle glaucoma (OAG) patients of African versus European descent (ED) over 4 years.<h4>Materials and methods</h4>In this study, 112 patients with OAG were examined at baseline, 79 [59 ED, 20 African descent (AD)] of which were followed for 4 years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured ...[more]

PMID: 27561102

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Project description:PurposeBoth non-arteritic anterior ischemic optic neuropathy (NAION) and primary open-angle glaucoma (POAG) damage retinal ganglion cell axons, which are perfused by the radial peripapillary capillaries. To evaluate the pattern of ischemia, we compared peripapillary capillary density (PCD) in NAION eyes to POAG eyes matched for visual field mean deviation and retinal nerve fiber layer thickness.Methods31 chronic NAION (>6 months after the acute event) and unaffected fellow eyes (31 subjects), 42 moderate and severe POAG eyes (27 subjects), and 77 control eyes (46 healthy subjects) were imaged with a commercial optical coherence tomography angiography system (AngioVue, Avanti RTVue-XR, Optovue, CA) at two academic institutions. Two concentric circles of diameters 1.95mm (inner) and 3.45mm (outer) were manually placed on images centered on the optic nerve head, producing an annular region-of-interest. Image analysis with major vessel removal was performed using a custom program. Whole-image, whole-annulus, and sectoral PCDs were measured.ResultsWhole-image and whole-annulus PCDs in NAION and moderate and severe POAG eyes were significantly decreased compared to unaffected fellow eyes and control eyes (all P<0.001). Superior and temporal PCD values were affected more than other sectors in both NAION and POAG groups compared to control group. Whole-image and whole-annulus PCDs were not statistically different between NAION and POAG eyes (both P = 0.99). However, of all peripapillary sectors, the inferior sector PCD value was less affected in POAG eyes compared to NAION eyes (P = 0.001). Univariate analysis results also revealed a significant positive correlation between superior and inferior PCDs and corresponding RNFL thicknesses. The inferior sector correlation was greater in POAG than NAION eyes.ConclusionWhile the whole PCD values were not different in chronic NAION and POAG, the greater correlation of inferior PCD with corresponding RNFL sectors in POAG compared to NAION suggests greater susceptibility of the inferior radial peripapillary capillary in the pathogenesis of POAG.

Project description:PurposeTo find genetic contributions to glaucoma in African Americans.DesignCross-sectional, case-control study.ParticipantsOne thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine.MethodsMegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs).Main outcome measuresPrimary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946).ResultsEighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 β, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively.ConclusionsA novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

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Dataset Information

Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent.

Publications

Reductions in Retrobulbar and Retinal Capillary Blood Flow Strongly Correlate With Changes in Optic Nerve Head and Retinal Morphology Over 4 Years in Open-angle Glaucoma Patients of African Descent Compared With Patients of European Descent.

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