Combining OCT and OCTA for Focal Structure-Function Modeling in Early Primary Open-Angle Glaucoma.
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ABSTRACT: Purpose
To investigate modeling of the focal visual field (VF) loss by combining structural measurements and vascular measurements in eyes with early primary open-angle glaucoma (POAG).Methods
In this cross-sectional study, subjects with early glaucoma (VF mean deviation, ≥-6 dB) underwent optical coherence tomography (OCT) imaging, optical coherence tomography angiography (OCTA) imaging, and Humphrey 24-2 VF tests. Capillary perfusion densities (CPDs) were calculated after the removal of large vessels in the OCTA images. Focal associations between VF losses at the individual VF test locations, circumpapillary retinal nerve fiber layer (RNFL) thickness measurements from OCT, and CPDs were determined using nerve fiber trajectory tracings. Linear mixed models were used to model focal VF losses at each VF test location.Results
Ninety-seven eyes with early POAG (VF mean deviation, -2.47 ± 1.64 dB) of 71 subjects were included. Focal VF modeling using a combined RNFL-CPD approach resulted in a median adjusted R2 value of 0.30 (interquartile range [IQR], 0.13-0.55), whereas the RNFL-only and CPD-only approaches resulted in median values of 0.22 (IQR, 0.10-0.51) and 0.26 (IQR, 0.10-0.52), respectively. Seventeen VF locations with the combined approach had an adjusted R2 value greater than 0.50. Likelihood testing at each VF test location showed that the combined approach performed significantly better at the superior nasal VF regions of the eyes compared with the univariate approaches.Conclusions
Modeling of focal VF losses showed improvements when structural thickness and vascular parameters were included in tandem. Evaluation of VF defects in early glaucoma may benefit from considering both RNFL and OCTA characteristics.
SUBMITTER: Wong D
PROVIDER: S-EPMC8662568 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Combining OCT and OCTA for Focal Structure-Function Modeling in Early Primary Open-Angle Glaucoma.
Wong Damon D Chua Jacqueline J Tan Bingyao B Yao Xinwen X Chong Rachel R Sng Chelvin C A CCA Husain Rahat R Aung Tin T Garway-Heath David D Schmetterer Leopold L
Investigative ophthalmology & visual science 20211201 15
<h4>Purpose</h4>To investigate modeling of the focal visual field (VF) loss by combining structural measurements and vascular measurements in eyes with early primary open-angle glaucoma (POAG).<h4>Methods</h4>In this cross-sectional study, subjects with early glaucoma (VF mean deviation, ≥-6 dB) underwent optical coherence tomography (OCT) imaging, optical coherence tomography angiography (OCTA) imaging, and Humphrey 24-2 VF tests. Capillary perfusion densities (CPDs) were calculated after the r ...[more]
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Project description:PurposeTo evaluate the focal structure-function associations among visual field (VF) loss, optical coherence tomography angiography (OCT-A) vascular measurements, and optical coherence tomography (OCT) structural measurements in glaucoma.MethodsIn this cross-sectional study, subjects underwent standard automated perimetry, OCT-based nerve fiber thickness measurements, and OCT-A imaging. Mappings of focal VF test locations with OCT and OCT-A measurements were defined using anatomically adjusted nerve fiber trajectories and were studied using multivariate mixed-effects analysis. Segmented regression analysis was used to determine the presence of breakpoints in the structure-function associations.ResultsThe study included 119 eyes from 86 Chinese subjects with primary open-angle glaucoma (POAG). VF mean deviation was significantly associated with global capillary perfusion density (β = 0.13 ± 0.08) and global retinal nerve fiber layer thickness (β = 0.09 ± 0.02). Focal capillary density (FCD) was significantly associated with VF losses at 34 VF test locations (66.7% of 24-2 VF), with 24 of the 34 locations being within 20° of retinal eccentricity. Focal nerve layer (FNL) thickness was significantly associated with 16 VF test locations (31.4% of 24-2 VF; eight locations within 20° eccentricity). For VF test locations in the central 10° VF, VF losses below the breakpoint were significantly associated with FCD (slope, 0.89 ± 0.12, P < 0.001), but not with FNL thickness (slope, 0.57 ± 0.39, P = 0.15).ConclusionsFocal capillary densities were significantly associated with a wider range of visual field losses and in a larger proportion of the visual field compared to nerve fiber thickness.
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Project description:PurposeTo compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG).DesignCross-sectional study.ParticipantsEighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study.MethodsGlobal and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale.Main outcome measuresRetinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups.ResultsBoth global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P = 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P = 0.070]).ConclusionsAssociations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.
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Project description:A substantial fraction of glaucoma has a genetic basis. About 5% of primary open angle glaucoma (POAG) is currently attributed to single-gene or Mendelian forms of glaucoma (ie glaucoma caused by mutations in myocilin or optineurin). Mutations in these genes have a high likelihood of leading to glaucoma and are rarely seen in normal subjects. Other cases of POAG have a more complex genetic basis and are caused by the combined effects of many genetic and environmental risk factors, each of which do not act alone to cause glaucoma. These factors are more frequently detected in patients with POAG, but are also commonly observed in normal subjects. Additional genes that may be important in glaucoma pathogenesis have been investigated using quantitative traits approaches. Such studies have begun to identify genes that control the magnitude of important quantitative features of glaucoma that may also be important risk factors for POAG, such as central corneal thickness. Each of these different approaches to study glaucoma genetics is providing new insights into the pathogenesis of POAG.
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Project description:PurposeTo evaluate the association between OCT-angiography (OCTA) and photopic negative response (PhNR) in open angle glaucoma (OAG) patients and assess the diagnostic accuracy of these parameters in early detection of glaucoma.MethodsA total of 152 eyes were enrolled in this study, 28 eyes with mild POAG (group I), 44 eyes with moderate-severe POAG (group 2) & 80 eyes of healthy subjects (control group). Full ophthalmological examination, OCTA and PhNR measurements were underwent for all participants. RNFL, GCC thicknesses, PhNR (implicit time and amplitude) were recorded. The superficial and deep capillary plexus vessel density (SCP-VD%, DCP-VD%) were measured by using 6 × 6 mm macula OCTA scans. The peripapillary vessel density (RPC-VD %) were measured by using 4.5 × 4.5 mm optic disk head OCTA scans.ResultsThere were reduction of the median Interquartile range (IQR) thickness of the GCC and RNFL in OAG eyes versus normal (P < 0.001). RPC-VD%, SCP-VD % and DCP-VD% were significantly reduced in OAG eyes versus normal (P < 0.001). Increased OAG severity was associated with more reduction in PhNR amplitude and increased implicit time. Reduced PhNR amplitude and prolonged latency were significantly correlated with reduced vascular parameters. The RCP-VD and PhNR amplitude demonstrated higher diagnostic accuracy (98.7) with the largest AUC and higher sensitivity and specificity (100% & 98.7%, respectively), followed by the PhNR implicit time with (AUC = 0.995) with a diagnostic accuracy 98.7. The SCP-VD, RNFL and GCC thickness had a diagnostic accuracy of (75.0, 81.6 & 84.2), respectively (P < 0.001).ConclusionsOCTA vascular parameters displayed significant positive correlation with PhNR amplitude and significant negative correlation with PhNR implicit time. OCTA and PhNR parameters showed a high diagnostic accuracy for detection of glaucoma, and both may provide promising insight in early detection of glaucoma. This study was retrospectively registered on ClinicalTrials.gov (identifier, NCT05104294).
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Project description:AimTo estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that reported blindness rates for both PACG and POAG.MethodA systematic search was performed in PubMed for articles published in English between 2000 and 2020 reporting the prevalence of POAG as well as PACG among various ethnic populations. A study was included if it was (1) population-based (2) had published prevalence and blindness rates for both PACG and POAG in the same cohort. (3) Glaucoma was defined as per the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) criteria. The proportion of blindness for both POAG and PACG for each study and the cumulative proportion taking all the studies were calculated.ResultsWe included 23 studies with 78,434 participants. POAG was diagnosed in 1702 persons with 151 (8.9%) blind. There were 724 cases of PACG with 196 (27.0%) blind. The risk ratio of blindness in PACG to POAG varied from 0.73 to 10.6 among the studies. The cumulative risk ratio was 2.39 (95% confidence interval (CI); 1.99, 2.87). Risk ratios for studies including visual field restriction while defining blindness were similar to studies that did not (1.92 vs 2.64, P = 0.11). Risk ratios were also similar for studies that used greater than 2 instead of 3 or more quadrants of iridotrabecular contact to define angle closure (2.79 vs 2.25).ConclusionPrimary angle-closure disease is more likely to be associated with blindness.
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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
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