Bruch’s membrane opening-minimum rim width and visual fi eld loss in glaucoma: a broken stick analysis
INTRODUCTION
Glaucoma is a chronic optic neuropathy characterized by the progressive decrease of retinal ganglion cells (RGCs) and their axons, resulting in thinning of the neuroretinal rim of the optic nerve head (ONH) and retinal nerve fi ber layer (RNFL), and eventually leading to visual field(VF) defects[1].
The diagnosis of glaucoma and the detection of progression are based on a combination of structural and functional tests[2-3].However, discordance between structural and functional testing should be expected in patients with glaucoma[4-5].Optic disc damage and RNFL defects may precede the beginning of glaucomatous VF loss[6-7]. Kerrigan-Baumrind et al[8] reported that a 25%-35% RGC loss was associated with statistical abnormalities in automated VF testing. Other studies have reported that a 8%-42% RNFL loss, as measured using spectral-domain optical coherence tomography (SDOCT), was required for functional loss to be detectable[9-10].Most importantly, detection of early structural changes that can precede VF loss is fundamental to the long-term preservation of vision in glaucoma patients[6-10].
The SD-OCT enabled clinicians to characterize the ONH anatomy in relation to the clinical optic disc margin[11].Recently, Reis et al[12] introduced a new anatomical parameter of neuroretinal rim, Bruch’s membrane opening-minimum rim width (BMO-MRW), which quantifies the neuroretinal rim from BMO’s inner end and accounts for the variable trajectory of RGC axons at the measurement points. This parameter consists of the shortest distance between the BMO and the internal limiting membrane (ILM), and has been reported to yield better diagnostic accuracy and more accurate structurefunction relationship than the disc margin-based rim area[13-16].However, none of these studies identified the threshold value of the BMO-MRW at which the functional loss as measured with standard automated perimetry can be detected. Therefore,the purpose of this study was to determine the BMO-MRW tipping point at which the VF loss was detectable and related to structural changes.
SUBJECTS AND METHODS
Participants In this retrospective, cross-sectional study, open angle glaucoma patients and normal subjects who were seen at the Glaucoma Clinic at Pusan National University Hospital between August 1, 2015 and January 31, 2016 were included.The study was conformed to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board(IRB) of Pusan National University Hospital. The written consent from patients was waived by IRB because this is a retrospective,anonymous study. When both eyes of a participant were eligible,one eye was randomly chosen for inclusion in the study.
All of the enrolled glaucoma patients and healthy subjects underwent a complete ophthalmic examination, including measurement of the best-corrected visual acuity (BCVA), a slit-lamp examination, gonioscopy, funduscopy, biometry using an IOL Master (Carl Zeiss Meditec, Dublin, CA, USA),and standard automated perimetry. Central corneal thickness was measured using ultrasonic pachymetry (Pachmate; DGH Technology, Exton, PA, USA). Keratometry and spherical equivalent were measured with an Auto Kerato-Refractometer(ARK-510A; NIDEK, Hiroishi, Japan). All of the patients were also examined using red-free RNFL photographs,optic disc stereoscopic photographs, and SD-OCT images(Spectralis; Heidelberg Engineering, Heidelberg, Germany).The inclusion criteria for the participants included an age >18y with a clear cornea and clear ocular media, a BCVA≥20/40, a refractive error within ±6.0 diopters (D) of 0, and astigmatism±3.0 D of 0. Exclusion criteria included diabetes, uveitis,secondary glaucoma, corneal abnormalities, non-glaucomatous optic neuropathies, previous trauma, ocular surgery or laser treatment, or any other eye disease other than glaucoma. Eyes were classified as having open angle glaucoma if they had a glaucomatous optic disc and two consecutive abnormal VF test results with open angles on gonioscopy. Glaucomatous optic neuropathy was defined as having a >0.2 cup-to-disc ratio asymmetry between the two eyes, neuroretinal rim thinning, notching, or characteristic RNFL defects indicative of glaucoma[17]. Healthy subjects were recruited among those who visited this hospital for regular health check-ups or refractive errors. They were defined as those with no history of ocular disease, an intraocular pressure <21 mm Hg, an absence of glaucomatous optic disc appearance, and a normal VF. Subjects who were clinically suspected to have glaucoma because of ONH or RNflappearance, or elevated intraocular pressure but with normal VF were included in the healthy subjects to ensure representation of the full spectrum of disease.
![pagenumber_ebook=124,pagenumber_book=829](https://qkk.lw71.com/uploads/image/2018/5/af333a02957228e3c0c659b465c18058.png)
Figure 1 Garway-Heath sectorization of Bruch’s membrane opening-minimum rim width and corresponding VF threshold values ST: Superotemporal sector; T: Temporal sector; IT: Inferotemporal sector; IN: Inferonasal sector; N: Nasal sector; SN: Superonasal sector.
Normal subjects had a Glaucoma Hemifield Test (GHT) within normal limits and a mean deviation (MD) and pattern standard deviation (PSD) within 95% of HFA’s normative database. An abnormal VF was defined as P<0.05 for the PSD or a GHT result outside of the normal limits. The total deviation (TD)values were recorded in all of the 52 testing points (points matching the blind spot were excluded) and then assigned to the corresponding VF sector according to the Garway-Heath distribution map[18]. The TD values in dB unit was first converted to linear (1/Lambert) scale with the following formula; 1/Lambert =10dB/10, then averaged in each sector, and converted back to the decibel scale for analysis[19] (Figure 1).
Perimetric Tests All VF tests were performed with an automated VF analyzer (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA, USA) with a 24-2 pattern and a size III white stimulus using the Swedish Interactive Threshold Algorithm (SITA) standard strategy. Reliable tests were defined as <20% fixation loss rate, <15% false-positive rate,and <33% false-negative rate.
A proportion of neuroretinal rim area may comprise nonneural rim tissue, such as glia and blood vessels[38]. A floor effect will therefore influence the structure-function relationship in advanced glaucoma[33]. A fl oor effect was not identified in this study, since the study sample consisted of eyes with early to moderate structural damage[10].
综上所述,宫腔镜手术中通过对围术期血糖的监测,能够有效预防水中毒并发症的发生,做到早发现、早治疗,大大提高了宫腔镜手术的安全性。
Statistical Analysis The normality of the data distribution was checked using the Kolmogorov-Smirnov test. Clinical characteristics of the study population were compared using Student’s t-test or the Mann-Whitney U test for continuous variables, and the χ2 test for categorical variables.
挥发性风味物质中的双乙酰、乙醛和乳酸对酸奶风味贡献突出,并对酸奶的气味和口感起到重要作用。酸奶中β-半乳糖苷酶与乳酸脱氢酶对乳酸的生成影响很大,可以通过调节酶活控制酸奶后酸化问题。β-半乳糖苷酶、α-乙酰乳酸脱羧酶、葡萄糖激酶、乳糖通透酶和丙酮酸激酶的酶活对酸奶中双乙酰、乙醛的产量有很大相关性。探究酸奶中的酶与挥发性风味物质的关系,有助于酸奶风味物质的形成机理研究。
The results in this study were consistent with the earlier studies, which reported that substantial structural loss was necessary before functional VF defects became detectable[6-10].Wollstein et al[9] reported that a loss >17.3% of the mean RNFL thickness was necessary for the VF defect to be detectable.The authors reported that losses of 27.8% and 25.8% of RNFL thickness in the superior and inferior quadrants, respectively,were necessary before the VF defect was detectable[9].Alasil et al[10] demonstrated that detectable VF defects were associated with 42.3% and 14.5% thinning of the RNFL thickness in the inferior and superior quadrants, respectively.They also found that the temporal quadrant showed the lowest percentage RNFL loss needed to detect the central VF loss[9-10].The normal neural rim width is thickest in the inferior region,followed by the superior, nasal and temporal regions (ISNT rule)[24]. We showed that the BMO-MRW values also followed the ISNT rule in normal subjects. It can therefore be inferred that sectors with the thicker BMO-MRW may require more structural loss for corresponding functional abnormality to be detectable[9-10]. The number of axons passing through the temporal region of the optic disc was significantly larger than other regions because of the high concentration of thinner axons in the papillomacular bundle[9,25]. Based on our study,this might lead to the development of VF damage after a smaller BMO-MRW loss.
RESULTS
One hundred sixty-eight participants (85 normal and 83 glaucoma subjects) were enrolled in the study. The demographic, clinical,and ocular characteristics of the participants are summarized in Table 1. The global BMO-MRW of the glaucoma patients was significantly thinner than that of the normal subjects,256.3±48.9 μm for the normal subjects and 163.8±37.9 μm for the glaucoma patients (P<0.001). The number of glaucoma patients whose sectoral BMO-MRW values followed the ISNT rule was si gni fi cantly lower than the normal subjects, with 31(36.5%) for the normal subjects and 3 (3.6%) for the glaucoma patients (P<0.001; Table 2). The global indices of the VF for glaucoma patients were significantly worse than the normal subjects. The VF MD was -1.22±1.91 dB for the normal subjects and -7.06±5.38 dB for glaucoma patients (P<0.001).Scatterplots of the global, sectoral BMO-MRWs and corresponding VF TD values are shown in Figures 2 and 3.A range of BMO-MRW values was unrelated to the VF TD values, followed by a range of BMO-MRW values which was strongly related to the VF TD values (Figure 2A).Statistically optimal locations of the tipping points between these two ranges in the global and sectoral BMO-MRW values are summarized in Table 3. The locations of the tippingpoints were statistically significant for all of the locations(all P≤0.006; Davies’ test). The percentages of BMO-MRW loss for the tipping points were calculated for the global and sectoral BMO-MRW values using the mean BMO-MRW values for the normal subjects. The tipping point for the global BMO-MRW measurement occurred after a 25.9% loss from the mean normal BMO-MRW value. Using sectoral analyses, the percentage of BMO-MRW loss was highest for the superonasal sector (34.9%) and was lowest loss for the temporal sector (6.6%), with a range of 8.9%-34.4% for all of the other sectors (Table 3).
Table 1 Demographic and clinical characteristics of the study groups based on the diagnosis in 168 eyes of 168 subjects
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aMann-Whitney U test; bχ2 test; cStudent’s t-test. VF: Visual fi eld; VFI:Visual fi eld index.
Age (y) 56.6±12.9 59.4±13.8 0.106a Female/male 43/42 39/44 0.647b Axial length (mm) 23.71±1.17 24.09±1.46 0.081c Central corneal thickness (μm) 552.4±39.0 543.3±37.4 0.132c Spherical equivalent (D) -0.94±2.37 -1.25±2.62 0.445a Intraocular pressure (mm Hg) 14.4±3.2 15.5±4.3 0.078a VF Mean deviation (dB) -1.22±1.91 -7.06±5.38 <0.001a Pattern standard deviation (dB) 1.90±1.38 6.77±4.15 <0.001a VFI (%) 98.49±2.64 81.71±16.77 <0.001a
Table 2 BMO-MRW values and the percentage of healthy and glaucoma subjects that met the ISNT rule for BMO-MRW μm; mean±SD
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aMann-Whitney U test; bStudent’s t-test; cχ2 test; dThe number of patients whose BMO-MRW values met the ISNT rule. The ISNT rule was met when the BMO-MRW was thickest based on the average of the two inferior quadrants, followed by the average of the two superior, nasal, and then temporal quadrants. BMO-MRW: Bruch’s membrane opening-minimum rim width.
Global 256.3±48.9 163.8±37.9 <0.001b Superotemporal 254.0±56.8 160.4±53.8 <0.001b Temporal 185.1±42.6 131.6±41.2 <0.001b Inferotemporal 283.1±51.3 140.8±63.3 <0.001a Superonasal 297.1±66.7 191.1±57.6 <0.001b Nasal 272.0±64.0 184.4±46.9 <0.001a Inferonasal 307.7±59.3 178.3±57.1 <0.001b ISNT rule metd 31 (36.5%) 3 (3.6%) <0.001c
![pagenumber_ebook=126,pagenumber_book=831](https://qkk.lw71.com/uploads/image/2018/5/b334bbb7607e56fe51699f85a7254f6d.png)
Figure 2 Scatter plots of the global mean BMO-MRW with the corresponding VF total deviation values (A), mean deviation (B) and VFI(C) in healthy (empty squares) and glaucoma ( filled circles) eyes The 95%CIs for the tipping points and slopes are shown as dashed line. The tipping points are 189.8 μm (A), 185.0 μm (B) and 180.4 μm (C).
![pagenumber_ebook=126,pagenumber_book=831](https://qkk.lw71.com/uploads/image/2018/5/5fb6d08061159bc658d2193d2d54c305.png)
Figure 3 Scatter plots of healthy (empty squares) and glaucoma (filled circles) BMO-MRW in each sector with corresponding VF threshold values The 95%CIs for the tipping point and slopes are shown as dashed line.
Table 3 The global and sectoral BMO-MRW tipping points with percent loss from the average normal values
![pagenumber_ebook=126,pagenumber_book=831](https://qkk.lw71.com/uploads/image/2018/5/530179db156a62fe76919a7d49e64e98.png)
aAverage percent BMO-MRW thickness loss associated with each tipping point value. The normative values are from current study healthy group; bP value from Davies’ test which means the tipping point is statistically significant. BMO-MRW: Bruch’s membrane opening-minimum rim width.
BMO-MRW area BMO-MRW tipping point (95%CI)aLoss tipping point from normative (%)bP Global 189.8 (165.2 to 214.4) 25.9 <0.001 Superotemporal231.5 (193.1 to 269.8) 8.9 0.003 Temporal 172.9 (144.4 to 201.5) 6.6 0.006 Inferotemporal 189.3 (157.3 to 221.3) 33.1 <0.001 Superonasal 193.3 (154.7 to 231.8) 34.9 0.006 Nasal 178.4 (155.1 to 201.7) 34.4 <0.001 Inferonasal 231.7 (192.2 to 271.2) 24.7 <0.001
Determination of the actual location of the expected VF loss is clinically important in preserving vision in patients with suspected or preperimetric glaucoma[9-10,23]. We also found that substantial BMO-MRW thinning in inferotemporal sector (33.1%) and relatively less BMO-MRW thinning in the superotemporal sector (8.9%) were necessary for the detection of the VF loss. In the temporal sector, only 6.6% of the BMOMRW loss was necessary for the detection of the VF loss.
Globally, the tipping point was estimated at 189.8 μm (95%CI,165.2 to 214.4), with a slope above the tipping point of 0.009 dB/μm (95%CI, -0.002 to 0.019) and below the tipping point of 0.061 dB/μm (95%CI, 0.040 to 0.082). Using the same approach with the VF MD instead of the TD values, the tipping point was 185.0 μm (95%CI, 166.3 to 203.8) with a slope above the tipping point of 0.017 dB/μm (95%CI, 0.002 to 0.032) and below the tipping point of 0.121 dB/μm (95%CI,0.087 to 0.156), with a statistically significant differencebetween the slopes (P<0.001; Figure 2B). A similar segmented structure-function relationship was found using the visual field index (VFI). The tipping point was 180.4 μm (95%CI,165.7 to 195.0) with a slope above the tipping point of 0.045 dB/μm (95%CI, 0.004 to 0.087) and below the tipping point of 0.415 dB/μm (95%CI, 0.314 to 0.516), with a statistically significant difference between the slopes(P<0.001; Figure 2C).
Table 4 Slopes associated with the broken stick model used to determine the tipping point (point at which BMO-MRW thinning is first associated with VF loss)
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aP values for the slopes below and above the tipping point represent the statistical significance of the slopes being different than zero; bP values represent the statistical significance of the difference between the slopes below and above the tipping points. Values of fitted slopes below and above the tipping point are listed for global and quadrant BMO-MRW. BMO-MRW: Bruch’s membrane opening-minimum rim width.
BMO-MRW area Slopes below the tipping point(dB/μm)Slopes above the tipping point(dB/μm) Difference between the slopes Adjusted Slope 95%CI aP Slope 95%CI aP △Slope 95%CI bP Global 0.061 0.040 to 0.082 <0.001 0.009 -0.002 to 0.019 0.101 -0.052 -0.084 to -0.021 <0.001 0.3645 Superotemporal 0.036 0.024 to 0.048 <0.001 0.000 -0.017 to 0.016 0.951 -0.036 -0.065 to -0.008 <0.001 0.2929 Temporal 0.037 0.023 to 0.052 <0.001 -0.003 -0.021 to 0.015 0.748 -0.040 -0.073 to -0.008 <0.001 0.2027 Inferotemporal 0.091 0.068 to 0.115 <0.001 0.011 -0.005 to 0.027 0.191 -0.081 -0.120 to -0.041 <0.001 0.5264 Superonasal 0.052 0.025 to 0.078 <0.001 0.007 -0.002 to 0.016 0.115 -0.045 -0.080 to -0.009 0.002 0.2136 Nasal 0.074 0.039 to 0.110 <0.001 0.003 -0.006 to 0.012 0.477 -0.071 -0.116 to -0.027 <0.001 0.1800 Inferonasal 0.085 0.056 to 0.115 <0.001 0.007 -0.015 to 0.028 0.530 -0.078 -0.130 to -0.028 <0.001 0.3425 R2
DISCUSSION
The main limitation of our study was its cross-sectional nature.Clinicians should be careful to apply our fi ndings to individual patients longitudinally. Patients may start with a thinner or thicker BMO-MRW, and their individual tipping points may differ from the value we reported. Another limitation was that the average normal BMO-MRW values were calculated from our study cohort. Clinicians should be aware that a normal BMO-MRW value and the percent loss for the tipping point may differ from large population-based data. All of the patients in our study population were Asian, so the structure-function relationship may be different in other ethnic populations.
The slopes for VF TD values as a function of BMO-MRWs above and below the tipping points and the differences between the slopes are summarized in Table 4. Above the tipping points,the slopes of the VF TD values to BMO-MRW values were not different from zero (i.e. the 95%CIs included zero) throughout all of the sectors and global BMO-MRW. However, the slopes below the tipping point were significantly different from zero throughout the all of the sectors and global BMO-MRW (all P<0.001). In addition, the slopes below the tipping point were significantly steeper than the slopes above the tipping point(superonasal sector, P=0.002; all other sectors, P<0.001).
本文在罗晶等人的研究成果基础之上,进一步研究,拟以生活中常见的颗粒状农产品大枣、花生和开心果为主要研究对象,对常用的线阵图像传感器得到的图像采用连通域标记算法对图像中的物体进行标记,以区别和判断该物体,然后对得到的图像进行特征提取和分析,采用KNN算法进行特征筛选,根据筛选出的最优特征值得到最能区分不同种类的农产品的本质特征,给出算法流程并对算法在PC端进行验证。设计原理框图如图1所示。
A scatterplot of the BMO-MRWs with the VF TD values showed a plateau of the VF at high BMO-MRW values and a steep decrease at lower BMO-MRW values. A nonlinear“broken stick” statistical model was used to fi t this scatter plot.An initial estimate of the tipping point was determined using Davies’ test[21], after which segment regression analyses were performed with this initial tipping point as a starting value.Using iteration of segment regression analyses to reduce error,the final tipping point and two slopes of the broken stick model with their corresponding 95% con fi dence intervals (CIs) were determined. All of the statistical analyses were performed using R language software (http://www.R-project.org) and the segmented R library[22]. A value of P<0.05 was considered statistically significant.
幼儿园阶段的教育是学生接受教育的开端与基础部分,对于学生未来的发展影响深远。但由于经济条件等多方面客观因素的影响,我国乡镇中心幼儿园普遍陷入师资力量匮乏,教师队伍管理问题层出不穷的窘境[1]。许多教师由于自身业务素养低,教学方法守旧,没有站在幼儿未来发展的角度思索自身的教育存在问题。因此,加强乡镇中心幼儿园教师队伍的管理势在必行。
In this study, the regression slopes of VF TD values to the BMO-MRW above the tipping points were not different from zero in all of the locations. These results are consistent with clinical experience and findings in the literature, suggesting that many patients may shoWevidence of ONH damage before functional loss such as VF is detected[7,26-27]. Similarly, there was a poor association of the RNFL thickness with the VF loss when the loss of RNFL thickness was not severe[9-10,28-30].Yu et al[31] found that progressive RNFL thinning strongly predicted a subsequent VF decline.
虽然已有学者对价值共创体系评价工作展开了诸多研究,但仍有不足之处。首先,已有研究以传统竞争环境为背景,以单个企业的资源和能力为理论基础,不适于当前的超竞争复杂动态环境,难以精确地描述价值共创体系中企业的持续竞争能力和环境适应能力。其次,基于传统理论的静态性价值共创体系评估方法无法真实评估企业价值创造体系的价值创造能力,基于系统视角对企业价值共创体系评价的研究没有充分考虑企业价值共创体系的动态演化和涌现的整体系统特征。
We showed that the slopes of the VF TD values to the BMOMRW below the tipping point were significantly steeper than the slopes above the tipping point for all of the locations. It is possible that a strong clinical relationship between structure and function may be detected only after the redundancy of RGC function was exhausted[32]. The reasons for the discordance in structure-function relationship in our study were likely because standard automated perimetry had higher variability than OCT during the early development of glaucoma[19,33]. Because of the redundancy of VF sensitivity, damage occurred without showing early abnormalities[32-33]. In addition, global indices of the VF such as MD and VFI are insensitive to localized loss[34] and less able to detect early glaucoma because of the ceiling effect[35]. Gardiner et al[36] reported that both structural and functional tests were associated with significant intraindividual and inter-test variability, and the weak structurefunction relationship in ocular hypertension or suspected/early glaucoma could be explained by variability in testing. Subtle rotation of eye and head tilt can skew the OCT measurement,and each sectoral mean may differ without any actual changes in the ONH[37]. However, Spectralis OCT uses TruTrack™that uses dual beam technology to compensate for possible eye motion to reduce the measurement variability[10,20]. Taken together, the results suggested that a combination of structural and functional assessment are very important in the evaluation of the early glaucomatous damage and disease progression in patients with glaucoma[10,14,33].
Recently, an anatomically and geometrically accurate rim parameter based on the BMO was reported[12-13,15]. This new parameter, termed the BMO-MRW, quantifies the neuroretinal rim from the actual anatomical outer border and accounts for the variable orientation of the rim tissue in ONH[12-13,15].The BMO-MRW has better diagnostic accuracy[13] and a stronger relationship to the VF than the RNFL thickness and other neuroretinal rim measurement[14-15]. Chauhan et al[13]reported that at 95% specificity, the sensitivity of the RNFL thickness, BMO-HRW, and BMO-MRW was 70%, 51%,and 81%, respectively. Pollet-Villard et al[14] reported that the structure-function relationship with the BMO-MRW was stronger than that with either the RNFL thickness or the Cirrus high de fi nition OCT based neuroretinal rim measures.Danthurebandara et al[15] reported that the structure-function relationship was stronger with the BMO-MRW than with the disc margin-based rim area and the BMO based horizontal rim width (BMO-HRW). Our study differed from previous studies that used a single linear or logarithmic regression model to evaluate structure-function relationship with the BMO-MRW[14-15]. In contrast to these previous studies, our study used the broken stick tipping point model to show that the BMO-MRW had a strong association with VF loss. We also performed analyses using the MD and VFI since they are commonly used functional parameters in clinical practice. The tipping points for MD and VFI occured at a BMO-MRW value of 185.0 μm and 180.4 μm, respectively.
Spectral-domain Optical Coherence Tomography Imaging SD-OCT was performed on all of the subjects on the same day as the perimetric test. Scans were acquired according to the participant’s specific fovea-BMO axis to minimize the geometrical errors[15], and the data were sectorized according to this axis. The fovea position was manually located with a live B-scan, followed by the two BMO points in each of two radial B-scans that were perpendicular to each other. A radial pattern containing 24 angular, equidistant, high-resolution 15° B-scans centered on the BMO was used to compute the neuroretinal rim parameters. Each B-scan was averaged from 25 individual scans with 1536 A-scans per B-scan with a scanning speed of 40 000 A-scans per second[10,20]. The BMO points and ILM were identified and marked in each B-scan with automated software (Glaucoma Module Premium Edition, version 6.0;Heidelberg Engineering) and corrected when necessary. Eyes with an image quality score <20 were excluded. BMO-MRW,the minimum distance between the BMO and ILM, was automatically computed globally and sectorally according to the Garway-Heath distribution map corresponding to the VF sectors[18]. The Spectralis OCT used TruTrack™ that used dual beam technology to compensation for eye motion[10,20]. One beam captured an image of the retina and mapped over 1000 points to track eye movement. With this map as a reference,the second beam was directed to the desired location despite of eye movements.
We determined the relationship between the BMO-MRW and VF sensitivity using the broken stick tipping point model.We identified the tipping point where the VF abnormality was associated with the BMO-MRW loss. Overall, the result showed that a substantial BMO-MRW loss (25.9% loss from the average normal global value) was necessary to detect the VF loss.
In conclusion, using “broken-stick” analyses, we identified the tipping point between the BMO-MRW and VF sensitivities in this study. Particularly in early glaucoma, functional loss of vision as measured by standard automated perimetry can be masked until significant structural damage has progressed. We suggest that the tipping point is approximately a 25.9% loss from normal global BMO-MRW values. Therefore, the BMOMRW measurement may help clinicians to make early decisions regarding a reliable treatment plan before any VF abnormality is detected in the early phases of glaucomatous damage.
ACKNOWLEDGEMENTS
Authors’ contributions: Conceptualization: Park KH, Lee JW; Data curation: Park KH, Kim JM; Formal analysis: Park KH; Investigation: Lee JW; Methodology: Lee JW, Kim JM; Project administration: Lee JW; Resources: Lee JW;Software: Park KH; Supervision: Lee JW; Validation: Lee JW;Visualization: Park KH; Writing-original draft preparation:Park KH; Writing-review & editing: Lee JW.
从RTA涉及成员国的发展水平来看,发达国家之间签订的RTA条款质量总体上高于发展中国家之间的RTA,发达国家和发展中国家间签订的RTA的质量介于中间位置。例如,美国—韩国的双边RTA在WTO+和WTO-X领域的条款覆盖率为86%和55%,而东盟—韩国为71%和40%,东盟—中国RTA仅达到了57%和5%。
(5)3台快开式压滤机,处理面积300 m2;2台西班牙进口压滤机,处理面积280 m2,单台处理能力20~22 t/h(5个循环/h),但由于煤泥难沉淀,煤泥水粘度大时,每小时只能进行2个循环,而且成饼效果差。
Con flicts of Interest: Park KH, None; Lee JW, None; Kim JM, None; Nouri-Mahdavi K, None; Caprioli J, None.
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