Intereye and intraeye asymmetry analysis of retinal microvascular and neural structure parameters for diagnosis of primary open-angle glaucoma.
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SUBMITTER: Xu H
PROVIDER: S-EPMC7002640 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Intereye and intraeye asymmetry analysis of retinal microvascular and neural structure parameters for diagnosis of primary open-angle glaucoma.
Xu Huan H Zong Yuan Y Zhai Ruyi R Kong Xiangmei X Jiang Chunhui C Sun Xinghuai X
Eye (London, England) 20190503 10
<h4>Purpose</h4>To investigate the diagnostic values of intereye or intraeye asymmetry of retinal perfused vessel density and neural structure parameters for detection of glaucoma.<h4>Methods</h4>In total, 152 healthy subjects and 72 bilateral primary open-angle glaucoma (POAG) patients were enrolled. Total POAG group contains all glaucoma patients. Early to moderate POAG group contains patients whose binocular mean defect values were larger than -12 dB. The retinal perfused vessel densities wer ...[more]
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Project description:PurposeTo investigate the relationship between intereye visual field defect (VFD) asymmetry and subsequent VF progression in primary open-angle glaucoma (POAG).MethodsModerate-stage patients with POAG (226 eyes of 113 patients) with a single hemifield defect were followed for 8.7 years. Participants were categorized into three groups by initial VF pattern: (1) unilateral VFD, (2) bilateral VFD within same hemifield (superior-superior, inferior-inferior), (3) bilateral VFD within opposite hemifield (superior-inferior). The mean deviation (MD) difference between the intereye was defined as the intereye MD asymmetry index (iMAI). Intereye visual-sensitivity difference within the same hemifield was calculated as the intereye hemifield visual-sensitivity asymmetry index. Functional progression was detected by Glaucoma Progression Analysis. The overall rate of MD change and the association between new indices were evaluated by linear regression. A Kaplan-Meier survival analysis was performed and the factors associated with glaucoma progression were evaluated by Cox proportional hazard modeling.ResultsUnilateral VFD eyes and bilateral VFD eyes within opposite VF hemifield showed significant progression and faster rate of MD change compared with bilateral VFD eyes within same VF hemifield (71.1% vs. 45.9% vs. 21.1% [P = 0.001]; -1.27 dB/y vs. -0.64 dB/y vs. -0.32 dB/y [P = 0.001]). Unilateral VFD eyes showed the fastest time to VF progression compared with other groups (P = 0.002). A faster rate of MD change was associated with greater intereye MD asymmetry index (P = 0.001) and greater intereye hemifield visual-sensitivity asymmetric index (P = 0.031), which were significant risk factors for glaucoma progression (all P < 0.001).ConclusionsAmong POAG eyes with comparable hemifield VFDs, eyes without a corresponding hemifield defect in the fellow eye showed faster rates of progression compared with those with a corresponding hemifield defect.
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Project description:PurposeTo characterize intereye differences in posterior segment parameters and determine their significance in open-angle glaucoma patients with unilateral damage.MethodsBoth eyes from 65 subjects without any nerve damage and 43 patients undergoing treatment for unilateral open-angle glaucoma were included in this study. A 12.0×9.0×2.6 mm volume of the posterior segment in each eye was scanned with swept-source optical coherence tomography. Coronally reconstructed optical coherence tomography images were analyzed to determine the deepest point of the eye (DPE), which we then calculated the distance (Disc-DPE distance), depth (Disc-DPE depth), angle (Disc-DPE angle) from the optic disc center to the DPE. Posterior pole shape was analyzed measuring the posterior pole-cross-sectional area, posterior pole-horizontal width (PP-HW), and posterior pole-vertical width) of the posterior pole. These measurements and their intereye absolute difference (IAD; absolute difference in measurements between the right and left eyes) values were compared between the healthy and unilateral glaucomatous patients.ResultsThe posterior sclera measurements, including the Disc-DPE distance, Disc-DPE depth, and posterior pole-cross-sectional area, were significantly different between the unilateral glaucoma eyes and contralateral healthy eyes (P=0.043, P=0.035, and P=0.049, respectively). By contrast, none of the intereye differences in optic nerve head parameters were significant in the unilateral glaucoma patients. In comparison with the IAD values, the baseline intraocular pressure and PP-HW of the posterior segment showed significant differences between the healthy and the unilateral glaucoma patients (P=0.019 and P=0.036, respectively). A multivariate analysis showed that a larger baseline intraocular pressure IAD [odds ratio (OR), 1.381; P=0.009)] and larger PP-HW IAD (OR, 1.324; P=0.032) were significantly associated with the presence of glaucoma.ConclusionsCompared with the fellow healthy eyes, glaucomatous eyes had larger and more steeply curved posterior poles, which represent a structural variation of the posterior sclera that might be associated with glaucomatous optic neuropathy.
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Project description:BackgroundPrimary open-angle glaucoma (POAG) is associated with systemic microvascular dysfunction including hemorrhages and other abnormalities of the nailfold capillary bed. This study aimed to verify the specificity of nailfold capillary hemorrhages and other abnormalities as risk factors for POAG.MethodsNailfold video capillaroscopy was performed using a JH-1004 capillaroscope on the fourth and fifth digits of the nondominant hand in control (n?=?277), POAG (n?=?206), OHT (n?=?57), and SG (n?=?29) subjects. The number of hemorrhages, dilated capillaries >50?µm, and avascular zones ?200?µm were counted and adjusted to counts per 100 capillaries. Descriptive analyses as well as univariate- and multivariable-adjusted logistic regression were performed comparing all groups with controls and POAG with OHT and SG. Subanalyses were conducted in POAG patients examining the association between nailfold capillary outcomes and previous glaucoma surgery, successful IOP control, or disease severity.ResultsAll nailfold capillary outcomes were significantly increased in POAG, no outcomes were increased in SG, and only hemorrhages were mildly increased in OHT. Hemorrhages were significantly more frequent in POAG compared with both OHT (P < 0.0001) and SG (P=0.001). There were significant trends between higher numbers of hemorrhages and POAG compared with controls, OHT, and SG, with odds ratios of 18.3 (8.5-39.4), 9.1 (1.9-13.4), and 11.8 (1.7-7.3), respectively, for the presence of two or more hemorrhages per 100 capillaries. Hemorrhages were not significantly associated with previous glaucoma surgery, successful postoperative IOP control, or disease severity in POAG.ConclusionsThese findings suggest that systemic microvascular dysfunction is frequent in POAG and occurs early in the disease process. The high specificity of nailfold hemorrhages makes them viable clinical risk factors for POAG.
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Project description:Purpose:To characterize the corneal biomechanical properties of glaucoma eyes by comparing the dynamic Scheimpflug biomechanical parameters between untreated glaucoma and control eyes. Methods:Cross-sectional observational data of dynamic Scheimpflug analyzer (Corvis ST) examinations were retrospectively collected from 35 eyes of 35 consecutive patients with untreated normal tension glaucoma and 35 eyes of 35 healthy patients matched on age and IOP. Ten biomechanical parameters were compared between the two groups using multivariable models adjusting for IOP, central corneal thickness, age, and axial length. The Benjamini-Hochberg method was used to correct for multiple comparison. Results:In multivariable models, glaucoma was associated with smaller applanation 1 time (P < 0.001, coefficient = -0.5865), applanation 2 time (P = 0.012, coefficient = -0.1702), radius (P = 0.006, coefficient = -0.5447), larger peak distance (P = 0.011, coefficient = 0.1023), deformation amplitude ratio at 1 mm (P < 0.001, coefficient = 0.072), and integrated radius (P < 0.001, coefficient = 1.094). These associations consistently indicate greater compliance of the cornea in glaucoma eyes. Conclusions:Untreated normal tension glaucoma eyes were more compliant than healthy eyes. The greater compliance (smaller stiffness) of normal tension glaucoma eyes may increase the risk of optic nerve damage. These results suggest the relevance of measuring biomechanical properties of glaucoma eyes.
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Project description:PurposeThe Glaucoma Stereo Analysis Study (GSAS), a cross sectional multicenter collaborative study, used a stereo fundus camera to assess various morphological parameters of the optic nerve head (ONH) in glaucoma patients and investigated the relationships between these parameters and patient characteristics.Subjects and methodsThe study included 187 eyes of 187 subjects with primary open angle glaucoma or normal tension glaucoma (male: female ?=?100: 87, age ?=?61±9 years). Stereo pairs of ONH photographs were made with a stereo fundus camera (nonmyd WX). ONH morphological parameters were calculated with prototype analysis software. In addition to 35 standard parameters, we defined three novel parameters: disc tilt angle, rim decentering, and the absolute value of rim decentering. The correlation between each parameter and patient characteristics was analyzed with Spearman's rank correlation coefficient.ResultsPatient characteristics included refractive error of -3.38±3.75 diopters, intraocular pressure (IOP) of 13.6±2.6 mmHg, and visual field mean deviation (MD) of -4.71±3.26 dB. Representative ONH parameters included a horizontal disc width of 1.66±0.28 mm, vertical disc width of 1.86±0.23 mm, disc area of 2.42±0.63 mm2, cup area of 1.45±0.57 mm2, and cup volume of 0.31±0.22 mm3. Correlation analysis revealed significant negative associations between vertical cup-to-disc ratio (0.82±0.08) and MD (r?=?-0.40, P<0.01) and between disc tilt angle (10.5±12.5 degrees) and refractive error (r?=?-0.36, P<0.01). Seventy-five percent of the eyes had a positive value for rim decentering (0.30±0.42), indicating that rim thinning manifested more often as an inferior lesion than a superior lesion.ConclusionWe used stereoscopic analysis to establish a database of ONH parameters, which may facilitate future studies of glaucomatous changes in ONH morphology.
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Project description:The total RNA from control and POAG optic nerve lamina cribrosa region was isolated and subjected to analysis on U133A 2.0 affymetrix microarray chip. The results from these two analysis was compared to determine whether PAD II RNA level is altered. Purpose of the study. This study was done to determine which RNA transcripts undergo significant changes in the optic nerve between normal and cadaver primary open-angle glaucoma donors. Using donor tissues from NDRI we have performed proteomic analyses (which will be published shortly), we intend a comparison between the proteomic and RNA changes for select proteins in our study. Sample Collection and Preparation of Labeled Copy RNA; The total RNA from optic nerve was obtained using TRIZOL (Invitrogen Inc., Carlsbad, CA) with modification of recommended protocols. The optic nerve from donor eyes were carefully excised and minced into small pieces first using a scissor and then a scalpel. Prior to use tissue was washed with DEPC water and all solutions were prepared in DEPC water. The minced tissue was placed in a glass homogenizer with 1 ml TRIZOL per 100 mg of tissue and homogenized in a glass homogenizer DUALL 20 (Kimble Kontes Glass Co, Vineland, NJ) with 10 strokes cycles each at room temperature and after freezing with liquid nitrogen for 1 min for 40 cycles. This RNA was extracted with chloroform, isoamylalcohol and precipitated with sodium citrate/sodium chloride and isopropanol. The final air-dried RNA precipitate was suspended in DEPC water and stored in â??80oC prior to use. RNA was prepared for hybridization according to the GeneChip Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA). The hybridization was performed at Gene Expression Array Core Facility at Case Western Reserve University (www.geacf.net). The RNA sample was cleaned using a column from a Qiagen RNeasy kit, (part # 74104 ) in accordance with the manufacturerâ??s instructions. The volume of DEPC water used to elute the RNA from the Qiagen column was dictated by the nominal mass of the loaded RNA sample. Samples were eluted in 100ml of water, precipitated with 0.5 volume of 7.5M Ammonium Acetate and 2.5 volumes of 100% ethanol at -20oC for 1 hr and centrifuged for 10 min at room temperature. The pellet was drained and washed twice in 500µl of 70% ethanol. Supernatant was aspirated. The pellet was dried briefly (less than 1 min) in a speeedvac (Savant) and re-suspended in a small volume (~ 12â??15ml) of DEPC water. A small aliquot (2ml) of the sample was used for quantitation. Cleaned RNA samples were annotated as â??clnRNAâ?? and stored at -20oC. cDNA Synthesis; The protocol recommended by Affymetrix Inc. for cDNA synthesis was used at all times. The reaction was primed by annealing an oligo-dT primer coupled to a T7 RNA polymerase promoter to the RNA sample. Whenever possible, 8 mg of clnRNA were reverse transcribed using Superscript II reverse transcriptase in a 20ml reaction at 42oC for 1 hr. Second strand synthesis was carried out immediately in a total reaction volume of 150ml in the presence of E. coli DNA polymerase I, RNAse H and DNA ligase. The reaction mixture incubated for 2 hrs at 16oC and for a further 5 min in the presence of T4 DNA pol.. The reaction was terminated by the addition of EDTA. The sample was cleaned with a Qiagen cDNA clean-up column according to the manufacturers directions. The elution buffer volume was 14ml. The eluted samples were stored overnight at -20oC. In-Vitro Transcription (IVT) reaction; In a 0.5ml microfuge tube, complementary RNA (cRNA) was generated in an IVT reaction using a BioArray High Yield ENZO kit (Affymetrix). The 40ml reaction contained 10ml of cDNA sample and was incubated at 37oC in the heating block for 4-5hrs. Samples were mixed by flicking, pulse-centrifuged and returned to the incubator once every 40 minutes. Upon completion of the reaction, IVT samples were adjusted to a volume of 100ml with DEPC-treated water and cleaned using Qiagen RNA clean-up columns. Samples were eluted in 45ml of DEPC-treated water. A 2ml-aliquot was used for quantitation. Corrected concentrations of cRNA (minus the input clnRNA) were determined. A standard fragmentation reaction volume was 40ml in a 0.5 ml microfuge tube and used 20mg of overall IVT RNA in 1X fragmentation buffer (40mM Tris acetate, pH 8.1, 100mM KOAc, 30mM MgOAc). The reaction was incubated at 94oC for 35min in a heat block. After the 35 min incubation the fragmented samples were placed on ice. The standard hybridization cocktail volume was 300ml. 150ml of 2X hybridization buffer was added (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20) Herring sperm and acetylated BSA were added to a final concentration of 0.1 and 0.5mg/ml respectively. The amount of fragmentation reaction containing 15mg of cRNA was added to the cocktail and the remaining volume was made up with molecular biology grade water. A 15ml aliquot of a 20X mixture of in-vitro transcripts of bacterial genes BioB BioC BioD and cre as external controls (spikes) were added to the cocktail to give final concentrations of 1.5, 5, 25 and 100pM respectively. Control oligonucleotide (5ml) was added to a final concentration of 50pM. Array Hybridization; Sample Hyridization cocktails (300ml) were removed from storage at â??20oC and thawed in a 45oC temperature block. The samples were incubated at 45oC for 5 min, incubated at 45oC for 5 min and then centrifuged at 15,000g for 5 min. This study used commercially available Affymetrix HG U133A 2.0 arrays only. These are in situ synthesized, high density oligonucleotide arrays which can interrogate 22,777 gene entities. The part number is 900444 more detailed information may be found at www.affymetrix.com website. Meanwhile, the affymetrix chip arrays were taken from their storage at 4oC and allowed to come to room temperature. The chamber was filled with 1X hybridization buffer (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20). The chip was then preconditioned by incubation in the hybridization oven at 45oC for 10 min. The chip was removed and the chamber drained. Sample cocktails (200ml) were then introduced into the chamber of the chips. The ports were sealed with tough-spots stickers and placed in the hybridization oven and incubated at 45oC with rotation overnight. Next day (16hr later), the incubation was terminated and the chips removed from the oven. Samples were retrieved from the chips and stored again in a freezer at -20oC. The chips were filled with buffer A and placed in a module of Fluidics 400 wash station. The chips were subjected to the Affymetrix â??EuKws4 ver 2â?? programmed series of stringent post hybridization washes, staining and post-staining washes in accordance with Affy protocols. Upon completion of the wash series (approximately 2 hrs), the chips were removed from the Fluidics station. The chips were inspected. Chips were scanned using an Agilent Gene Array scanner 3000 driven by Affymetrix GCOS software. Generation of Expression Values; Microarray Suite, version 5 (Affymetrix), was used to generate *.cel files, and a computer program (Probe Profiler, ver. 1.3.11; Corimbia Inc., Berkeley, CA) developed specifically for the GeneChip system (Affymetrix) was used to convert intensity data into quantitative estimates of gene expression for each probe set. The software identifies informative probe pairs, and down-weights the signal contribution of probe pairs that are subject to differential cross-hybridization effects or that consistently produce no signal. The software also detects and corrects for saturation artifacts, outliers, and chip defects. A probability statistic was generated for each probe set. The probability is associated with the null hypothesis that the expression level of the probe set is equal to zero (background). Genes not significantly expressed above background in any of the samples (P > 0.05) were
2008-06-12 | E-GEOD-2387 | biostudies-arrayexpress
Project description:PurposeTo assess the accuracy of intraocular lens (IOL) power prediction for cataract surgery with open angle glaucoma (OAG) and to identify preoperative angle parameters correlated with postoperative unpredicted refractive errors.Materials and methodsThis study comprised 45 eyes from 45 OAG subjects and 63 eyes from 63 non-glaucomatous cataract subjects (controls). We investigated differences in preoperative predicted refractive errors and postoperative refractive errors for each group. Preoperative predicted refractive errors were obtained by biometry (IOL-master) and compared to postoperative refractive errors measured by auto-refractometer 2 months postoperatively. Anterior angle parameters were determined using swept source optical coherence tomography. We investigated correlations between preoperative angle parameters [angle open distance (AOD); trabecular iris surface area (TISA); angle recess area (ARA); trabecular iris angle (TIA)] and postoperative unpredicted refractive errors.ResultsIn patients with OAG, significant differences were noted between preoperative predicted and postoperative real refractive errors, with more myopia than predicted. No significant differences were recorded in controls. Angle parameters (AOD, ARA, TISA, and TIA) at the superior and inferior quadrant were significantly correlated with differences between predicted and postoperative refractive errors in OAG patients (-0.321 to -0.408, p<0.05). Superior quadrant AOD 500 was significantly correlated with postoperative refractive differences in multivariate linear regression analysis (?=-2.925, R²=0.404).ConclusionClinically unpredicted refractive errors after cataract surgery were more common in OAG than in controls. Certain preoperative angle parameters, especially AOD 500 at the superior quadrant, were significantly correlated with these unpredicted errors.
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