INTRODUCTION

Glaucoma is the leading cause of irreversible blinding disease, characterized by loss of retinal ganglion cells(RGCs) followed by visual fi eld defects. Standard automated perimetry has become the clinical gold standard for diagnosis and follow-up of glaucoma. However, clinically detectable structural change can precede the onset of visual field loss by up to 5y[1]. Peripapillary retinal nerve fiber layer (RNFL)measurements by optical coherence tomography (OCT)have been known as a good structural parameter to detect glaucoma[2]. Nevertheless, the optic disc of high myopic eyes is often accompanied by tilting, and peripapillary atrophy, which hamper precise diagnosis of glaucoma[3-5]. Furthermore, several studies have demonstrated that high myopic patients frequently tend to have thinner RNFL than the normal population, leading to inaccurate diagnosis of glaucoma[6].

The macula is expected to be the best location to evaluate RGC changes, because more than 50% of all RGCs are concentrated and multilayered there and RGCs bodies are 10 to 20 times the diameter of their axons[7-9]. Macular ganglion cell complex(GCC) includes three retinal layers: inner plexiform layer(IPL), ganglion cell layer (GCL), and the RNFL, representing dendrites of the RGCs, cell bodies and axons. RNFL and GCL become thinner as RGCs die from glaucoma. Therefore, macular GCC measurement may have a good ability to detect glaucoma[7].Recent studies showed conflicting results about the ability of macular GCC thickness to detect glaucoma in high myopic eyes.Shoji et al[10-11] and Zhang et al[12] reported that the GCC thickness was better to the RNFL thickness to detect glaucoma in high myopic eyes, while Kim et al[13] and Choi et al[14] found there was no significant difference in the detection ability between RNFL and GCC thickness. In the present study, we used RTVue Fourier domain optical coherence tomography (FD-OCT) to compare the ability of macular GCC thickness and peripapillary RNFL thickness to diagnose glaucoma in high myopic eyes.

SUBJECTS AND METHODS

Participants The patients of this cross-sectional study came from the outpatient service of Beijing Tongren Eye Center, China, between November 2015 and April 2016, who satis fi ed the inclusion and exclusion criteria. The participants were consecutively enrolled as they presented, and obtained informed consent. The study was approved by the Institutional Ethics Committee of Beijing Tongren Eye Center and complied with the tenets of the Declaration of Helsinki.

另外，本课从贴近学生生活实际的家乡农特产入手，再到探索优良的繁殖技术改良家乡优质水果。学生体会着用科学技术的力量实现家乡的飞跃进步的自豪与骄傲，有助于塑成家国情怀这种必备品格，同时，再次加深爱国爱家乡、用知识兴家乡的责任和情怀。

All subjects underwent an ophthalmologic examination, including assessment of visual acuity (VA), intraocular pressure (IOP),slit-lamp biomicroscopy, gonioscopy, axial length (Lenstar LS900, Haag-Streit, Koeniz, Switzerland), noncycloplegic refraction (Autorefractor KR-8900, Topcon Corporation,Tokyo, Japan), stereoscopic optic disc photography (WX-3D,Kowa Optimed, Tokyo, Japan), dilated fundus examination and RTVue FD-OCT. Automated visual field examinations(Humphrey visual field analyser, 750i, SITA fast 30-2, Carl Zeiss Meditec, Jena, Germany) were performed in glaucoma patients. Refraction data were converted to spherical equivalents. The subjects were divided by the spherical equivalents into a high myopic group (≤-6.00 D) and a nonhigh myopic group (＞-6.0 D). Glaucoma patients with a bestcorrected visual acuity of 20/100 or better, and spherical equivalent ≤-6.00 D were included. Subjects without glaucoma with a best-corrected visual acuity of 20/25 or better were included.

Participants were excluded if any evidence suggested ocular surgery history, other diseases (e.g. uveitis, trauma, neuroophthalmological diseases, or retinal and/or choroidal diseases). For the purpose of this study, subjects were classified into three groups: high myopic glaucomatous (HMG) group,high myopic normal (HMN) group, and non-high myopic normal (NHMN) group.

6)关联度：γi=1/N×∑εi(k)，式中：γi为比较数列Xi对参考数列X0的关联度；N为评价指标个数。

Glaucomatous eyes were defined as those with a glaucomatous visual field defect and the appearance of a glaucomatous optic disc irrespective of the level of IOP. In the pattern deviation plot, when presenting three or more significant (P＜0.05)contiguous points with at least one at the P＜0.01 level on the same side of the horizontal meridian, it means a field defect.

Statistical Analysis Only the data of the left eye from each patient were used for analysis. Baseline characteristics were summarized in counts and proportions or mean±standard deviation (SD). χ2 tests or unpaired t-tests were used for comparisons between groups. Receiver operating characteristic(ROC) curves were constructed for RNFL and GCC parameters to diagnose glaucomatous eyes by plotting sensitivity versus one-specificity. The area under each ROC curve [area under the curve (AUC)] was calculated. The parameters with the largest AUC were selected from RNFL and GCC algorithms to compare diagnostic ability. The method of DeLong et al[15]was used to compare the largest ROC curve. Statistical analysis was performed using SPSS for Windows (version 19.0.0). P values less than 0.05 were considered statistically significant.

Table 3 shows the AUCs and the values with 95% con fi dence interval (CI) for detection of glaucomatous eyes. When using the HMN subjects as the normal control, the parameters with the largest AUC in GCC, and RNFL parameters were GLV(0.968), and average RNFL (0.855), respectively. The AUC of GLV was better than that of average RNFL (P＜0.001). The ROC curves of these selected parameters (GLV, and average RNFL) are depicted in Figure 1. While using the NHMN subjects as the normal control, the AUC of GLV increased to 1.000 (increased by 0.032), and the AUC of average RNFL added up to 0.990 (increased by 0.135).

As for the effect of myopia on the thickness of macular GCC measured by OCT, previous studies have obtained conflicting results. Ooto et al[20] found that there was not a correlation between axial length and macular GCC thickness, whereas some studies[25] including ours, showed a negative correlation between macular inner retinal layer thickness and axial length. We also found that there were significant differences in the average, superior, and inferior macular GCC thickness between the HMN and NHMN eyes. On one hand, retinal thinning associated with the extension of the retinal surface due to axial elongation. On the other hand, retinal thinning also associated with the projection artifact of the scanning area of the OCT instruments in HMN eyes. The measured thickness may change if a larger area is scanned in eyes with longer axis length. However, the influence of high myopia on GCC may be less than that on RNFL parameters, which was consistent with Shoji’s study[10]. Shoji et al[10] found that macular GCC thickness efficiently detected glaucoma in both high myopic and emmetropic eyes, and only peripapillary RNFL thickness had a decreased ability for glaucoma detection in high myopic eyes. Thus, it is very important to install a normal database from normal eyes with high myopia as internal data in OCT instruments.

During the enrollment period, a total of 157 eyes from 157 individuals who agreed to participate were examined. Ten eyes were excluded because of low signal strength scores. Sixteen eyes with high myopic were excluded owing to the presence of a macular hole (n=1) or epiretinal membrane (n=2) or macular retinoschisis (n=13). In the HMN group, seventeen eyes with axial length more than 29 mm were excluded from analysis.Thus, a total of 114 eyes of 114 participants were included in the analysis: 44 HMN subjects, 31 NHMN subjects, and 39 HMG patients. Table 1 summarizes the demographics and ocular characteristics of the subjects. The mean age among HMN subjects (29.6±8.8y) was significantly younger than that among HMG patients (36.9±11.3y; P=0.002). Between HMN group and HMG group, there was significant difference in sex (P＜0.001), besides, central corneal thickness, axial length, and refraction (spherical equivalent) revealed no significant differences. Between NHMN subjects and HMG patients, age, sex, and central corneal thickness showed no significant differences, and there were significant differences in axial length and refraction (spherical equivalent; P＜0.001).The mean defects of visual fi eld were -1.6±1.7 in the NHMN subjects, and were -12.3±9.8 in the HMG patients, and the differences between the two groups were significant different(P＜0.001).

本文引入非对称双指数跳扩散模型来刻画基础资产的价格变化。利用双指数分布的不对称性可以解释行为金融学中提及的一个金融事实:投资者对同等程度的市场好、坏消息的反应程度是不同的,也能够解释实证研究中的偏峰与厚尾现象。在此基础上运用Girsanov测度变换定理来简化定价过程中的期望计算。最后利用条件期望和全期望公式得到重置期权的解析定价公式。公式尽管看起来很复杂,但是它能够被迅速计算和近似,便于在实际市场中运用,具有很大的实用价值。

RESULTS

Optical Coherence Tomography Measurements The thickness of the RNFL and GCC was measured by RTVue FD-OCT (software version: 4.0), which acquires 26 000 A scans per second and has a 5 mm depth resolution in tissue.The RNFL thickness was determined by the optic nerve head(ONH) protocol comprising 12 radial scans 3.4 mm in length and 13 concentric ring scans ranging from 1.3 to 4.9 mm in diameter, all centered on the optic disc. The GCC thickness was determined by the GCC protocol comprising 15 vertical lines at 0.5 mm intervals and one horizontal line. The center of the GCC scan is shifted 0.75 mm temporally to improve sampling of the temporal periphery. Images with signal strength indicator (SSI) ＜40 (as suggested by the manufacturer)were excluded from the analysis.

Table 1 Characteristics of subjects

HMN: High myopic normal; NHMN: Non-high myopic normal; HMG: High myopic glaucomatous.

P Parameters HMN(n=44)NHMN(n=31)HMG(n=39)HMN vs NHMN Age (y) 29.6±8.8 (19-51) 37.7±6.7 (22-51) 36.9±11.3 (18-65) 0.002 0.730 ＜0.001 Female, n (%) 32 (72.7) 16 (51.6) 12 (30.8) ＜0.001 0.077 0.061 Central corneal thickness (μm) 525.8±37.9 (460-590)545.4±27.3 (505-600)543.7±34.3 (485-630) 0.053 0.860 0.057 Axial length (mm) 27.1±1.1 (25.5-28.4) 23.5±0.7 (22.2-24.3) 26.9±0.8 (25.6-28.7) 0.695 ＜0.001 ＜0.001 Refraction (spherical equivalent; D)-7.8±1.6 (-6.0 to -12.5)-0.8±1.3 (0.5 to -4.0)-7.9±1.9 (-6.0 to -14.0) 0.742 ＜0.001 ＜0.001 HMN vs HMG NHMN vs HMG

Table 2 Perimacular GCC and peripapillary RNFL thickness abtained using RTVue OCT

GCC: Ganglion cell complex; RNFL: Retinal nerve fi bre layer; FLV: Focal loss volume; GLV: Global loss volume; HMN: High myopic normal;NHMN: Non-high myopic normal; HMG: High myopic glaucomatous; OCT: Optical coherence tomography.

P HMN vs NHMN GCC Average (μm) 94.17±5.65 100.28±4.45 73.38±12.81 ＜0.001 ＜0.001 ＜0.001 Superior (μm) 95.11±5.03 99.83±4.53 76.46±14.94 ＜0.001 ＜0.001 ＜0.001 Inferior (μm) 93.25±6.89 100.71±4.59 70.34±12.43 ＜0.001 ＜0.001 ＜0.001 FLV (%) 0.85±1.56 0.53±0.38 10.57±8.49 ＜0.001 ＜0.001 0.188 GLV (%) 4.48±3.97 1.02±0.74 27.14±11.21 ＜0.001 ＜0.001 ＜0.001 RNFL Average (μm) 94.04±8.74 109.55±6.53 75.68±13.88 ＜0.001 ＜0.001 ＜0.001 Superior (μm) 113.56±18.21 136.61±15.26 94.94±21.58 ＜0.001 ＜0.001 ＜0.001 Temporal (μm) 83.81±12.16 81.32±7.58 59.84±18.79 ＜0.001 ＜0.001 0.278 Inferior (μm) 113.81±18.47 139.81±13.71 88.27±19.62 ＜0.001 ＜0.001 ＜0.001 Nasal (μm) 65.11±12.28 79.29±14.83 60.18±14.17 0.097 ＜0.001 ＜0.001 Parameters HMN NHMN HMG HMN vs HMG NHMN vs HMG

Both the average macular GCC thickness and average peripapillary RNFL thickness showed negative correlations with axial length (rGCC=-0.404, P=0.001; rRNFL=-0.561,P＜0.001). Table 2 summarizes the distribution of GCC thickness and RNFL thickness in the three groups. In the HMG eyes, the average, superior, inferior GCC thickness were significantly thinner both than the HMN eyes and the NHMN eyes (all P＜0.001). Focal loss volume (FLV) and global loss volume (GLV) were also significantly different compared with both the HMN eyes and the NHMN eyes (all P＜0.001). When comparing GCC parameters between the HMN group and the NHMN group, except for focal loss volume, the others showed significant differences (all P＜0.001).

In the HMG eyes, except nasal RNFL thickness, the average,superior, inferior, and temporal RNFL thickness were significantly thinner both than the HMN eyes and the NHMN eyes (all P＜0.001). In the HMN eyes, except that the temporal RNFL thickness was thicker than that in the NHMN eyes(P=0.278), all the other parameters were significantly thinner than that in the NHMN eyes (all P＜0.001).

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DISCUSSION

With the reduction of infectious ocular diseases, glaucoma has become an important cause of blindness in China[16]. In this study, we confirmed that macular GCC thickness has better ability than that of peripapillary RNFL thickness to discriminate glaucoma patients from non-glaucoma subjects in high myopic subgroups.

日益增多的研究表明，家庭环境因素对儿童心理行为发展有着重要的作用，对儿童期乃整个成人期的智能水平、社会适应能力、性格、行为均有重大的影响［5－7］。以家庭系统运作效果为核心的 Mc－Master家庭功能模式理合认为家庭的基本功能是为家庭成员生理、心理、社会性等方面的健康发展提供一定的环境条件，适应并促进家庭及其成员各方面的发育和发展［8］。一个相对独立的系统，系统内部运转方式及规则、各系统组成成分的特点及相互作用方式，对于整体系统功能及各系统组成成分的影响都是显而易见的。家庭系统同样如此。

Table 3 AUC values with 95%CIs between normal and glaucomatous eyes

SE: Standard error; HMN: High myopic normal; NHMN: Non-high myopic normal; RNFL: Retinal nerve fi bre layer; FLV: Focal loss volume;GLV: Global loss volume; AUC: Areas under the curve.

Parameters AUC±SE (HMN) 95%CI P AUC±SE (NHMN) 95%CI P GCC Average (μm) 0.913±0.035 0.773-0.098 ＜0.001 0.971±0.020 0.932-1.000 ＜0.001 Superior (μm) 0.886±0.044 0.801-0.972 ＜0.001 0.927±0.036 0.856-0.998 ＜0.001 Inferior (μm) 0.938±0.027 0.886-0.991 ＜0.001 0.992±0.009 0.975-1.000 ＜0.001 FLV (%) 0.929±0.031 0.868-0.990 ＜0.001 0.945±0.031 0.884-1.000 ＜0.001 GLV (%) 0.968±0.017 0.934-1.000 ＜0.001 1.000±0.000 1.000-1.000 ＜0.001 RNFL Average (μm) 0.855±0.042 0.773-0.938 ＜0.001 0.990±0.010 0.971-1.000 ＜0.001 Superior (μm) 0.730±0.056 0.621-0.840 ＜0.001 0.942±0.025 0.892-0.991 ＜0.001 Temporal (μm) 0.853±0.042 0.770-0.935 ＜0.001 0.851±0.047 0.758-0.944 ＜0.001 Inferior (μm) 0.836±0.045 0.748-0.924 ＜0.001 0.978±0.016 0.948-1.000 ＜0.001 Nasal (μm) 0.633±0.063 0.509-0.707 0.037 0.872±0.044 0.786-0.958 ＜0.001

Figure 1 A comparison of areas under receiver operator characteristics curves of high myopic eyes in glaucoma for the GLV and average RNFL.

in agreement with previous reports[13-14,21]. The possible reasons may be as follows. Myopia affects the distribution of the RNFL thickness around the optic disc[13]. With raising myopia,the inferotemporal and superotemporal RNFL bundles tend to converge temporally[8,22]. Therefore, GCC measurements may be theoretically superior to RNFL parameters in high myopic glaucoma. Our results validated this point. We found that AUCs for the GCC-GLV and average RNFL were 0.968 and 0.855, respectively, and the difference was statistically significant. The present study implies that the macular GCC thickness attained higher diagnostic power than peripapillary RNFL thickness to detect glaucoma in high myopic patients.This result was in line with other fi ndings[10-11].

The internal normative database in current OCT instrument didn’t include high myopic eyes. The average RNFL thickness become thinner to distant to optic disc because of a magnification effect of longer axial length leading to scan larger area. Thus values of AUC for average RNFL were better in NHMN eyes than HMN eyes. Our results indicate that the use of RNFL thickness to detect HMG may lead to false positive diagnosis when using the internal database.These fi ndings are consistent with previous observations[23-24].Therefore, using the internal database may lead to improper interpretation of RNFL thicknesses when evaluating glaucoma with high myopia.

Normal eyes were defined as those with IOP ＜21 mm Hg, no family history of glaucoma and intraocular surgery, and no retinal diseases, and no glaucomatous optic neuropathy. Two independent masked glaucomatous specialists defined normal appearance of the optic disc. In the case of a disagreement, a third specialist reviewed the stereo photographs and made a determination.

Ten years ago, some studies have focused macula to detect glaucoma from normal subjects. Because of low discriminating power of time domain (TD)-OCT, those studies tested total macular thickness and showed that peripapillary RNFL were more advantageous than macular parameters. FD-OCT allows more detailed and precise quantitative assessment ofglaucomatous structural changes[17]. FD-OCT make it possible to image and measure macular GCC. In glaucomatous eyes,macular thickness decline is believed to be due to the loss of RGCs. Recent studies have demonstrated that macular GCC thickness had comparable diagnostic power with peripapillary RNFL thickness for glaucoma detection[18-19]. However, in high myopic eyes, the RNFL thickness was significantly affected by refractive errors, and its ability to detect glaucoma was inferior to that in emmetropic eyes. In our study, the average, superior,inferior, and nasal peripapillary RNFL along with all of the macular GCC thickness were significantly thinner in the HMN group than that in the NHMN group, although the HMN group included a younger population on average. It is established that the RNFL thickness and macular GCC thickness decrease with aging[20]. Whereas the temporal RNFL was thicker in the HMN group than that in the NHMN group. These fi ndings are

In conclusion, the macular GCC thickness had better ability to detect glaucoma in high myopia than peripapillary RNFL thickness from FD-OCT, although both the macular GCC thickness and peripapillary RNFL thickness were related with axial length. Thus, GCC assessment might be one of the best parameters for diagnosing highly myopia glaucoma. It would be more precise for glaucoma detection in high myopic patients if a normal database in high myopic eyes was available.

ACKNOWLEDGEMENTS

The authors acknowledge Professor Ning-Li Wang in Department of Ophthalmology, Beijing Tongren Hospital,Capital Medical University, who gave us help to complete this study.

Foundation: Supported by the National Natural Science Foundation of China (No.81500719).

Conflicts of Interest: Wang WW, None; Wang HZ, None;Liu JR, None; Zhang XF, None; Li M, None; Huo YJ, None;Yang XG, None.

（7）碾压。面层碾压分为初压、复压和终压。初压采用钢轮压路机碾压1遍，碾压速度为1.5～2.0km/h；复压采用胶轮压路机碾压2遍，碾压速度为2.5～3.5km/h；终压采用钢轮压路机碾压2遍，碾压速度为2.5～3.5km/h。

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