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An objective structural and functional reference standard in glaucoma.

ABSTRACT: The current lack of consensus for diagnosing glaucoma makes it difficult to develop diagnostic tests derived from deep learning (DL) algorithms. In the present study, we propose an objective definition of glaucomatous optic neuropathy (GON) using clearly defined parameters from optical coherence tomography and standard automated perimetry. We then use the proposed objective definition as reference standard to develop a DL algorithm to detect GON on fundus photos. A DL algorithm was trained to detect GON on fundus photos, using the proposed objective definition as reference standard. The performance was evaluated on an independent test sample with sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and likelihood ratios (LR). The test sample had 2118 fundus photos from 585 eyes of 405 individuals. The AUC to discriminate between GON and normal was 0.92 with sensitivity of 77% at 95% specificity. LRs indicated that the DL algorithm provided large changes in the post-test probability of disease for the majority of eyes. A DL algorithm to evaluate fundus photos had high performance to discriminate GON from normal. The newly proposed objective definition of GON used as reference standard may increase the comparability of diagnostic studies of glaucoma across devices and populations.

SUBMITTER: Mariottoni EB

PROVIDER: S-EPMC7814070 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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An objective structural and functional reference standard in glaucoma.

Mariottoni Eduardo B EB Jammal Alessandro A AA Berchuck Samuel I SI Shigueoka Leonardo S LS Tavares Ivan M IM Medeiros Felipe A FA

Scientific reports 20210118 1

The current lack of consensus for diagnosing glaucoma makes it difficult to develop diagnostic tests derived from deep learning (DL) algorithms. In the present study, we propose an objective definition of glaucomatous optic neuropathy (GON) using clearly defined parameters from optical coherence tomography and standard automated perimetry. We then use the proposed objective definition as reference standard to develop a DL algorithm to detect GON on fundus photos. A DL algorithm was trained to de ...[more]

PMID: 33462288

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Project description:PurposeTo investigate structural and functional correlations in glaucoma patients using optic nerve head hemoglobin (ONH Hb) measurements as determined by automated colorimetric analysis of conventional retinography.MethodsWe prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (standard automated perimetry, SAP), color fundus imaging (mydriatic retinography), and peripapillary retinal nerve fiber layer (pRNFL) assessment through spectral-domain optical coherence tomography (SD-OCT). Software Laguna ONhE was used to estimate the amount of ONH Hb and to determine the glaucoma discriminant function (GDF) index. Scatter plots were constructed, and regression analysis was used to investigate the correlations between GDF, average pRNFL thickness, and VF mean deviation (VFMD) index values. A secondary analysis was performed to compare each parameter between three different glaucoma groups divided according to VFMD values (mild, >-6 dB; moderate, -6 to -12 dB; and advanced, <-12 dB).ResultsOne hundred ninety-six eyes from 123 participants (69 with glaucoma and 54 controls) were enrolled. Overall, all parameters evaluated differed significantly between glaucomatous and control eyes (p ≤ 0.001). The comparison of each parameter according to groups of disease stages revealed significant differences between controls and each of the glaucomatous groups (p < 0.001). More pronounced changes in GDF values were observed in early disease stages. We found significant nonlinear correlations between GDF and VFMD values (R 2 = 0.295, p < 0.001) and between pRNFL thickness and VFMD (R 2 = 0.598, p < 0.001). A linear correlation was found between GDF and pRNFL thickness values (R 2 = 0.195, p < 0.001).ConclusionOur results showed significant associations between ONH Hb values and both structural and functional damage in glaucoma obtained by SD-OCT and SAP, respectively. The nonlinear correlation we found and the GDF behavior along different disease stages suggest that ONH Hb levels' reduction may precede visual function changes in early glaucoma stages.

Project description:Abstract: BACKGROUND: Obtaining reliable and reproducible two-color microarray gene expression data is critically important for understanding the biological significance of perturbations made on a cellular system. Microarray design, RNA preparation and labeling, hybridization conditions and data acquisition and analysis are variables difficult to simultaneously control. A useful tool for monitoring and controlling intra- and inter-experimental variation is Universal Reference RNA (URR), developed with the goal of providing hybridization signal at each microarray probe location (spot). Measuring signal at each spot as the ratio of experimental RNA to reference RNA targets, rather than relying on absolute signal intensity, decreases variability by normalizing signal output in any two-color hybridization experiment. RESULTS: Human, mouse and rat URR (UHRR, UMRR and URRR, respectively) were prepared from pools of RNA derived from individual cell lines representing different tissues. A variety of microarrays were used to determine percentage of spots hybridizing with URR and producing signal above a user defined threshold (microarray coverage). Microarray coverage was consistently greater than 80% for all arrays tested. We confirmed that individual cell lines contribute their own unique set of genes to URR, arguing for a pool of RNA from several cell lines as a better configuration for URR as opposed to a single cell line source for URR. Microarray coverage comparing two separately prepared batches each of UHRR, UMRR and URRR were highly correlated (Pearson's correlation coefficients of 0.97). CONCLUSION: Results of this study demonstrate that large quantities of pooled RNA from individual cell lines are reproducibly prepared and possess diverse gene representation. This type of reference provides a standard for reducing variation in microarray experiments and allows more reliable comparison of gene expression data within and between experiments and laboratories. This SuperSeries is composed of the SubSeries listed below.

Project description:PurposeTo analyze the correlation between structural characteristics of intraorbital optic nerve (ION) and lateral geniculate nucleus (LGN) measured by 3-Tesla magnetic resonance imaging (3T MRI), and the severity of glaucomatous damage.MethodsIn this cross-sectional study, 41 glaucoma patients and 12 age- and sex-matched controls underwent standard automated perimetry (SAP) and frequency doubling technology (FDT) as functional evaluation; optic disc stereophotograph, spectral-domain optical coherence tomography (OCT) and confocal scanning laser tomography as ocular structural evaluation; and 3T MRI. Structure-structure and structure-function correlation were performed using bootstrap resampling method for clustered data.ResultsThe ION mean diameter and cross-sectional area were different between glaucoma and control groups at 5mm and 10mm (all, p?0.011) from the globe, but not at 15mm (both, p?0.067). LGN height was significantly lower in glaucoma group (p = 0.005). OCT rim area and functional parameters (SAP and FDT) correlated significantly with all ION segments, showing stronger correlations at 10 and 15 mm. ION parameters at 10 and 15 mm presented mild-to-moderate correlation with OCT peripapillary nerve fiber layer thickness, and ION at 15mm had mild association with the neuroretinal rim area on stereophotographs. Although LGN height was significantly smaller in glaucoma group (p = 0.005), LGN parameters were not associated with any ocular structural or functional parameter.ConclusionAssessment of central and peripheral nervous systems using 3T MRI confirmed that glaucoma patients had smaller ION dimensions and LGN height compared to the control group. In general, ION dimensions presented mild to moderate correlations with functional and ocular structural parameters. Although ION had significant correlations at any distance from the eye, the ION distal locations correlated better with OCT results and functional parameters. However, LGN parameters were not associated with functional or ocular structural parameters.

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An objective structural and functional reference standard in glaucoma.

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An objective structural and functional reference standard in glaucoma.

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