Posterior Pole Asymmetry Analyses of Retinal Thickness of Upper and Lower Sectors and Their...

Yamashita et al. Symmetry of 64-cell retinal thicknesses by SD-OCT

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Title: 1

Posterior pole asymmetry analyses of retinal thickness of upper and lower 2

sectors and their association with peak retinal nerve fiber layer thickness in 3

healthy young eyes 4

5

Takehiro Yamashita, Taiji Sakamoto, Naoko Kakiuchi, Minoru Tanaka, Yuya Kii, 6

Kumiko Nakao 7

Department of Ophthalmology, Kagoshima University Graduate School of Medical 8

and Dental Sciences, Kagoshima, Japan 9

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Running head: Symmetry of 64-cell retinal thicknesses by SD-OCT 11

Corresponding author: Taiji Sakamoto, Department of Ophthalmology, Kagoshima 12

University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. Tel: 13

(81) 99-275-5402, Fax: (81) 99-265-4894. 14

e-mail: [email protected] 15

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Word count: abstract 250 words, text 3407 words. Figures: 5. Table: 1. 17

Supplementary Table: 3 18

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IOVS Papers in Press. Published on August 12, 2014 as Manuscript iovs.13-13828

Copyright 2014 by The Association for Research in Vision and Ophthalmology, Inc.


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PURPOSE: To determine the symmetry of the retinal thicknesses (RT) between 21

the 32 pairs of superior and inferior sectors by posterior pole asymmetrical analysis 22

(PPAA) of the spectral domain optical coherence tomographic (SD-OCT) images in 23

healthy eyes. In addition, to determine their association with the position of the 24

peak retinal nerve fiber layer (RNFL) thickness. 25

METHODS: A prospective observational cross sectional study of 64 right eyes. The 26

Spectralis SD-OCT was used to obtain the images, and the PPAA determined the 27

RT of the 64 cells within the central 24° area. The program also compared the 28

thicknesses of corresponding cells across the fovea-disc axis. Circular scans were 29

used to measure the supra- and infra-temporal RNFL peak angle differences (PADs). 30

The relationships between the RT of the corresponding cells and the relationship 31

between the differences of the RT of the corresponding cells and PAD were 32

investigated by linear regression analysis. 33

RESULTS: The mean differences between the RT of corresponding cells ranged 34

from 3.1 to 23.2 µm. The RT of all upper cells were significantly correlated with the 35

RT of the corresponding lower cells (R=0.45-0.97, P <0.001). The coefficients of 36

correlation between the corresponding pairs of central-macular and temporal-37

macular cells were higher than that of the peripheral and nasal-macular cells. The 38

differences of the pairs of nasal-macular cells RT were significantly correlated with 39

the PAD. 40

CONCLUSIONS: The symmetry of the RT between the upper and lower cells was 41

high in the central and temporal-macular areas but not in the peripheral and nasal-42

macular areas. 43

44


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Precis 45

46

Posterior pole analyses of healthy young eyes showed that the symmetry between 47

upper and lower retinal thicknesses in the central-macular and temporal-macular 48

areas was high but moderate in the nasal-macular area. Special caution is needed 49

when assessing the symmetry between these sectors in diseased eyes. 50

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INTRODUCTION 52

53

Evidence has been accumulating that the retinal thickness (RT) determined by 54

optical coherence tomography (OCT)1-3 is an important parameter for diagnosing 55

different types of retinal diseases.4-6 Recently, an asymmetry test, called posterior 56

pole asymmetry analysis (PPAA) by OCT, was introduced for diagnosing glaucoma 57

and is expected to improve the accuracy of diagnosing glaucoma.6 The PPAA, 58

installed in the Spectralis-OCT, can calculate the RT of 64 (8 x 8) cells within the 59

central 24° area and can also perform comparisons of the corresponding cells 60

across the fovea-disc axis. Its diagnostic accuracy was reported to be similar to 61

that obtained by retinal nerve fiber layer (RNFL) thickness circle scans.7-10 62

63

The PPAA is based on the hypothesis that the hemispherical symmetry of the RT is 64

altered by an asymmetrical thinning of the RNFL, ganglion cell layer, and inner 65

plexiform layer in glaucomatous eyes.6 However to the best of our knowledge, 66

there is no detailed report on the symmetry of the retinal thicknesses in normal 67

subjects especially in the data obtained by SD-OCT PPAA. An earlier study 68

showed that a significant correlation was present between the RNFL thicknesses of 69

the supra-temporal to infra-temporal cells across the fovea-disc axis.11 However, 70

the coefficient of determination was only 0.112, a correlation coefficient 0.335.11 In 71

addition, there were some healthy eyes with asymmetry of the thick retinal nerve 72

fiber bundles in the superior and inferior sectors. Thus, this asymmetry of the RNFL 73

thickness may not be rare or there may be a factor that alters the hemispherical 74

symmetry of the RT. 75

76


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To improve the diagnostic accuracy of PPAA, it is necessary to know the actual 77

symmetry of healthy eyes and the factors affecting the measurements. Thus, we 78

first investigated the relationship between corresponding cells across the fovea-disc 79

axis. Then, with the hypothesis that the deviation of RNFL peak affects the 80

hemispherical symmetry, the correlation of the RNFL peak and the RT symmetry of 81

healthy eyes was evaluated. 82

83

METHODS 84

85

All of the procedures used conformed to the tenets of the Declaration of Helsinki. A 86

written informed consent was obtained from all of the subjects after an explanation of 87

the procedures to be used. The study was approved by the Ethics Committee of 88

Kagoshima University Hospital, and it was registered with the University Hospital 89

Medical Network (UMIN)-clinical trials registry (CTR). The registration title was, 90

“Morphological analysis of the optic disc and the retinal nerve fiber in myopic eyes” 91

and the registration number was UMIN000006040. A detailed protocol is available 92

at https://upload.umin.ac.jp/cgi-open-93

bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R00000715494

&language=J. The results presented in this manuscript are part of the overall study. 95

96

Subjects 97

98

This was a cross sectional, prospective, observational study of 72 eyes of 72 99

volunteers that were examined between February 1, 2011 and February 20, 2012. 100

The volunteers had no eye diseases as determined by examining their medical 101


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history and our examinations. The data from only the right eyes were analyzed. 102

The inclusion criteria were: age ≥20 years but ≤40 years; eyes normal by slit–lamp 103

biomicroscopy, ophthalmoscopy, and OCT; best-corrected visual acuity of ≤0.1 104

logarithm of the minimum angle of resolution (logMAR) units; and intraocular 105

pressure (IOP) ≤21 mmHg. The exclusion criteria were: eyes with known ocular 106

diseases such as glaucoma, staphyloma, and optic disc anomaly; eyes of subjects 107

with known systemic diseases such as hypertension and diabetes; presence of 108

visual field defects; and prior refractive or intraocular surgery. None of the eyes 109

was initially excluded because of poor OCT image quality caused by poor fixation. 110

Seventy-two Japanese volunteers were screened for this project. One eye was 111

excluded due to a superior segmental optic disc hypoplasia, and two eyes because 112

of prior refractive surgery. Five other eyes were excluded because of segmentation 113

error in the retinal thicknesses. In the end, the right eyes of 64 individuals (42 men 114

and 22 women) were used for the analyses. 115

116

Measurement of axial length, refractive error, and RT of 64 sectors in posterior 117

pole 118

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All of the eyes had a standard ocular examination consisting of slit-lamp 120

biomicroscopy of the anterior segment, ophthalmoscopy of the ocular fundus, IOP 121

measurements with a pneumo-tonometer (CT-80, Topcon, Tokyo, Japan), and axial 122

length measurements with the AL-2000 ultrasound instrument (TOMEY, Japan). 123

The refractive error (spherical equivalent) was measured with the Topcon KR8800 124

auto-refractometer/keratometer. 125

126


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The retinal thickness was measured with the Spectralis SD-OCT (Heidelberg 127

Engineering, Germany) using the images obtained by PPAA scans. In this protocol, 128

the OCT instrument automatically draws a line connecting the center of the fovea 129

and the center of the optic disc as a reference line. Then, 61 line scans (1024 A 130

scans/line) parallel to the reference line within the central 25° x 30° are recorded. 131

In this protocol, B-scan observations were made by averaging 5 overlapping B-132

scans/image on each line scan. These 5 scans were used to obtain the RT values 133

for each cell. The embedded OCT software determined the distance between the 134

internal limiting membrane and the Bruch’s membrane and recorded this distance as 135

the RT. Then, 3D RT maps were created based upon these data. The quality of 136

the scans is indicated by a color scale at the bottom of the scanned images, and it 137

had to be in the green range to be considered a good quality scan. In addition, the 138

SD-OCT macular map provided a color scale representation of the topographic RT 139

which helped evaluate the image quality. Initially, we examined all of the B-scan 140

images of each eye to determine whether there were any segmentation errors in the 141

images. The following criteria were used to identify segmentation errors in the B-142

scans: obvious disruptions or abrupt 5% consecutive changes at a border or 20% 143

cumulative of the entire image.7,12 Five eyes were excluded because of 144

segmentation error in the RT. These excluded cases were perfectly matched by 145

these two methods, i.e., the color scale and B-scan images. 146

147

The average RT of each 8 by 8 (3° by 3°) sector which made up the 64 sectors was 148

determined. Our earlier study showed that the inter-observer and the inter-visit 149

reproducibilities of the PPAA were excellent.13 Therefore, one scan was sufficient 150

to measure the mean RT of the 64 cells in the PPAA scan. The 64 cells were 151


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numbered as in Figure 1. 152

153

Measurement of position of supra and infra temporal peak RNFL thickness 154

angles and calculation of difference between angles 155

The RNFL thickness was measured with the Spectralis SD-OCT using the RNFL 156

circle scan. The temporal-superior-nasal-inferior-temporal (TSNIT) thickness 157

curves were used to measure the angle between supra-temporal or infra-temporal 158

peaks of the RNFL thickness and the fovea-disc axis. We determined the peak 159

angles in the TSNIT thickness profile of the RNFL thickness analyses. The 160

distance between the peak RNFL thickness for the supra-temporal or infra-temporal 161

RNFL peaks and fovea-disc axis were determined by dragging a vertical line in the 162

profile graph in the Spectralis OCT software and Photoshop. The position of fovea-163

disc axis was determined as the intersection between the fovea-disc axis of the 164

PPAA scan and the scan circle of RNFLT. Then, the distance between the fovea-165

disc axis and supra-temporal (X1a+X1b of Figure 2) or infra-temporal RNFL peaks 166

(X2 of Figure 2) was converted to an angular value by dividing by the entire distance 167

(Y) and multiplying by 360 (Figure 2).14,15 The peak angle difference (PAD) was 168

calculated as the difference between the supra-temporal peak RNFL angle and the 169

infra-temporal peak RNFL angle. 170

171

Statistical Analyses 172

173

All statistical analyses were performed with the SPSS statistics 21 for Windows 174

(SPSS Inc., IBM, Somers, New York, USA). The relationships between the 32 175

corresponding upper and lower RT pairs were determined by the Pearson 176


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coefficients of correlation. The relationships between the RT of each of the 177

difference between corresponding upper and lower RT of 32 pairs and the PAD were 178

determined by the Spearman coefficients of correlation. 179

180

RESULTS 181

182

The mean ± standard deviation of the age was 26.0 ± 4.5 years (range, 22 to 40 183

years), and the mean refractive error (spherical equivalent) was -4.1 ± 3.1 diopters 184

(D) (range, -14.3 to 0.0 D). The mean axial length was 25.0 ± 1.3 mm (range, 22.4 185

to 28.2 mm), and the mean PAD was -1.9 ± 11.5 degrees (range, -27.4 to 23.5 186

degrees). The differences between corresponding upper and lower RT of the 32 187

pairs are shown in Figure 3. 188

189

Pearson coefficients of correlation between corresponding upper and lower 190

RT cells 191

192

The RTs of the corresponding upper and lower 32 pairs of cells were significantly 193

correlated (R = 0.45 to 0.97, P <0.001; Table 1). The correlation coefficients of the 194

pairs of central (12° by 12°) and temporal macular cells were higher than that of the 195

pairs of nasal-macular cells. 196


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197

198

Spearman correlation coefficient of differences between RT of corresponding 199

cells and PAD 200

201

The PAD was significantly correlated with the differences between corresponding 202

RTs of the 8 nasal pairs (R = 0.25 to 0.45, P <0.05) but was not significantly 203

correlated with the differences between the corresponding RTs of the central and the 204

24 temporal macular pairs (P >0.05; Table 1). 205

206

Correspondingcell number

Mean ± SD RangeAbsolute

valueMean ± SD

R p value R p value

1 3.2 ± 8.3 -19 ～ 25 6.6 ± 5.7 0.74 <0.001* 0.04 0.792 4.1 ± 9.2 -11 ～ 28 8.1 ± 6 0.75 <0.001* 0.07 0.603 3.7 ± 10.3 -21 ～ 27 8.7 ± 6.5 0.72 <0.001* 0.05 0.724 2.7 ± 12.2 -26 ～ 27 10.2 ± 7.1 0.66 <0.001* 0.18 0.155 2.8 ± 12.8 -26 ～ 27 10.5 ± 7.8 0.70 <0.001* 0.16 0.226 -3.9 ± 14.2 -39 ～ 24 11.8 ± 8.6 0.68 <0.001* 0.14 0.287 2.8 ± 15.1 -34 ～ 43 11.9 ± 9.7 0.64 <0.001* 0.11 0.398 21.5 ± 21 -21 ～ 66 23.2 ± 18.8 0.45 <0.001* 0.06 0.669 5.4 ± 7.8 -13 ～ 23 7.6 ± 5.6 0.77 <0.001* -0.14 0.2710 8 ± 9.1 -18 ～ 25 10.1 ± 6.7 0.74 <0.001* -0.08 0.5311 9.6 ± 8.3 -7 ～ 31 10.1 ± 7.7 0.80 <0.001* 0.01 0.9312 12.2 ± 7.6 -4 ～ 31 12.4 ± 7.2 0.85 <0.001* 0.22 0.0813 14.8 ± 8.4 -6 ～ 39 15 ± 8 0.84 <0.001* 0.25 0.04*14 7.9 ± 10.1 -24 ～ 30 10.7 ± 7.1 0.80 <0.001* 0.43 <0.001*15 -5 ± 14.3 -54 ～ 18 11.4 ± 9.9 0.72 <0.001* 0.45 <0.001*16 -2.5 ± 16.1 -34 ～ 29 13.3 ± 9.1 0.68 <0.001* 0.35 0.01*17 4.9 ± 7.4 -13 ～ 27 6.8 ± 5.7 0.81 <0.001* 0.07 0.5618 5.9 ± 7.1 -12 ～ 26 7.2 ± 5.8 0.86 <0.001* 0.21 0.1019 3.8 ± 8 -22 ～ 31 6.5 ± 5.9 0.86 <0.001* 0.08 0.5220 5.7 ± 7.3 -15 ～ 25 7.3 ± 5.6 0.89 <0.001* 0.10 0.4321 8.9 ± 8.4 -6 ～ 27 9.6 ± 7.6 0.87 <0.001* 0.19 0.1422 7.1 ± 8.4 -13 ～ 26 8.8 ± 6.6 0.87 <0.001* 0.25 0.05*23 6.7 ± 9 -11 ～ 26 8.9 ± 6.8 0.84 <0.001* 0.32 0.01*24 -3.1 ± 15.9 -43 ～ 32 12.8 ± 9.4 0.74 <0.001* 0.40 <0.01*25 0.2 ± 4.3 -13 ～ 10 3.3 ± 2.7 0.95 <0.001* -0.05 0.7126 -0.6 ± 4.2 -11 ～ 9 3.3 ± 2.7 0.96 <0.001* -0.01 0.9627 -3.9 ± 3.9 -16 ～ 3 4.2 ± 3.6 0.97 <0.001* 0.04 0.7628 -5.5 ± 11.3 -33 ～ 15 10 ± 7.6 0.77 <0.001* 0.24 0.0629 -0.5 ± 9.1 -26 ～ 17 7.1 ± 5.7 0.86 <0.001* 0.11 0.4130 0.8 ± 4 -13 ～ 9 3.1 ± 2.7 0.97 <0.001* 0.16 0.2231 4.8 ± 5.9 -14 ～ 28 5.8 ± 4.8 0.94 <0.001* 0.27 0.03*32 6.3 ± 11.1 -25 ～ 47 8.6 ± 8.9 0.81 <0.001* 0.05 0.69

SD: standard deviation, *:statistically significant correlation (p < 0.05)

Pearson correlation coefficient Spearman correlation coefficient

Difference between correspondingupper and lower cells retinal thickness

(μm)

Table 1. Difference and correlation between corresponfing upper and lower cells retinal thickness and its relationship with peakangle difference.

Corresponding upper and lowercells retinal thickness

Difference between correspondingcells retinal thickness and peak

angle difference


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DISCUSSION 207

208

Our results showed that the RT of cells in the temporal and central areas of the 209

central fundus were quite similar to the corresponding cells across the fovea-disc 210

axis, indicating that the symmetry was good in these areas. The differences in the 211

thicknesses between the upper and lower counterparts across the fovea-disc axis 212

was mostly less than 30 µm (2000/2048 cells, 97.7 %). Seo et al reported that the 213

diagnostic ability of PPAA for detecting localized RNFL defects was good with good 214

sensitivity.7 In their algorithm, a difference of 30 µm or greater was used as the 215

cutoff value for the cell-to-cell comparisons. The area under the receiver operating 216

characteristic (AUROC) of the PPAA based on the number of black cells was 0.958 ± 217

0.013 in 84 open angle glaucoma subjects with localized, wedge-shaped-RNFL 218

defects in the red-free RNFL photographs and 122 eyes of healthy subjects.7 This 219

cutoff value was selected based on the findings reported by previous studies.8,9 220

Because the symmetry of upper and lower cells was good with the values generally 221

less than 30 µm in healthy eyes in our study, this value would be reasonable and 222

acceptable. Additionally, because the differences of the corresponding cells in the 223

lateral macular area (cell numbers 25, 26, and 27) was very small in healthy eyes, 224

even a 10 µm cut-off value might be acceptable in identifying an alteration of the 225

symmetry for cells of that area in early glaucomatous eyes. For example, Um et al 226

divided the macular thickness values into those corresponding to the superior and 227

inferior macular thickness zones, and then evaluated the symmetry between 228

corresponding superior and inferior macular zones. They considered that the 229

results of these comparisons were more sensitive than the RNFL thickness for 230

detecting early stage glaucoma. The cutoff values of the zones, as obtained by 231


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comparison with reference group data varied, and the cutoff values of the temporal 232

zone (cell number 25, 26 and 27) were the smallest (7.7 µm).10 233

234

However, the symmetry was not well preserved in the nasal-peripheral macular 235

areas (number of corresponding cells: 1-10, 15, 16, 24), and the correlation 236

coefficient of nasal-peripheral macular area was less than that of the central- and 237

temporal-macular areas (number of corresponding cells: 11-14, 17-23, 25-32; Figure 238

4). In some cases, the differences were found to be greater than 30 µm, and these 239

eyes had asymmetry of the thick retinal nerve fiber bundles in the superior and 240

inferior sectors (Figure 5). 241

242

We assumed that the structural asymmetry between the supra- and infra-temporal 243

RNFL bundles across the fovea-disc axis may be the cause of these differences. 244

Thus, we compared the difference of the PAD across the fovea-disc axis and the 245

differences of the corresponding cells. Our findings showed that the differences of 246

the corresponding cells, e.g., paired-cells such number as 13, 14, 15, 16, and 22, 23, 247

24 and 31, were significantly and positively correlated with the difference of the PAD 248

(Figure 5). This is a new finding and can affect the accuracy of the diagnosis of 249

early stage glaucomatous eyes. 250

251

An earlier study showed that the sectorial retinal thickness was significantly 252

correlated with the axial length.13 Thus, the axial length may affect the relationship 253

between the superior and inferior retinal thickness. A partial correlation analysis 254

was performed to determine the relationship between the superior and inferior retinal 255

thicknesses with an exclusion of the effect of the axial length. The results showed 256


13

that even after excluding the effect of the axial length, the corresponding superior 257

and inferior cells retinal thickness were highly correlated (R = 0.30 to 0.96, P = 0.02 258

to <0.001, supplementary Table S1). 259

260

In the earlier study of the symmetry of retinal thicknesses between the upper-lateral 261

and lower-lateral areas, the correlation coefficient was 0.335 or a coefficient of 262

determination of 0.112 which is smaller than our results with a correlation coefficient 263

of 0.45 to 0.97. It is possible that the area studied earlier was larger than the area 264

studied in this study. This is important because the larger the area studied, the 265

greater will be the variations of the retinal thicknesses. Additionally, our subjects 266

were young and had healthy eyes. In addition, the ageing changes and media 267

opacities were minimal which could account for the higher coefficients of correlation. 268

269

Because the location of the large superior and inferior vessels are supposedly 270

located at the sites of the peak RNFL,15-17 and because these vessels are not 271

necessarily symmetrical across the fovea-disc axis, their locations can affect the 272

symmetry of upper and lower retinal thicknesses. We measured the supra- and 273

infra-temporal artery and vein angles in the RNFL thickness scan circle using the 274

same method as the peak RNFL locations. The artery angle difference (AAD) and 275

the vein angle difference (VAD) were calculated as the difference between the 276

supra-temporal artery or vein angles and the infra-temporal artery or vein angles. 277

The peak angle difference (PAD) was significantly correlated with the AAD (R = 0.44, 278

P <0.001) and the VAD (R = 0.32, P = 0.012). The AAD was significantly correlated 279

with the differences between corresponding RTs of the 5 nasal pairs (R = 0.26 to 280

0.33, P <0.05) but was not significantly correlated with the differences between the 281


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corresponding RTs of the other pairs (P >0.05; Supplementary Table S2). These 282

correlations on the relationship between the PAD and the difference between 283

corresponding RTs are weak. The VAD was significantly correlated with the 284

differences between corresponding RTs of only one pair (sector 31, R = 0.27, P = 285

0.03; Supplementary Table S2). These results suggest that the AAD can be 286

substituted for the PAD in assessing the symmetry between upper and lower retinal 287

thicknesses. They also indicate that the asymmetry of the superior and inferior 288

retinal artery position of the peripapillary area across the fovea-disc axis would break 289

the symmetry of the RT across the fovea-disc axis. 290

291

The angle of the fovea-disc axis may be correlated with the PAD. Therefore, we 292

investigated the fovea-disc angle and the relationship between the PAD and the 293

differences between corresponding RTs. The fovea-disc angle was calculated by 294

dividing the fovea disc axis (X1b of Figure 2) by the entire distance and multiplying 295

by 360 (Figure 2). The fovea-disc angle was significantly correlated with the 296

differences between corresponding RTs of the 8 nasal pairs (R = 0.26 to 0.42, P 297

<0.05) and one peripheral pair (R = 0.28, P = 0.02) but was not significantly 298

correlated with the differences between the corresponding RTs of the other pairs (P 299

>0.05; Supplementary Table S3). These results are similar to the correlations 300

between the PAD and the differences of the corresponding RTs. In addition, the 301

fovea-disc angle was significantly correlated with the PAD (R = -0.43, P <0.001). 302

These results suggest that the fovea-disc angle may be substituted for the PAD in 303

assessing the symmetry between upper and lower retinal thicknesses in the different 304

sectors. 305

306


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The earliest sign of glaucoma is usually a focal reduction of the retinal thickness of 307

the RNFL bundle especially in the superior or inferior lateral areas. The structural 308

asymmetry of these areas might interfere with the diagnostic accuracy of PPAA. 309

Indeed, Seo et al reported that the sensitivity and specificity of PPAA in detecting 310

localized RNFL defects using two, three, and four consecutive black cells (black 311

indicating differences of retinal thickness of >30 µm) were 95.2% vs 81.1%, 83.3% 312

vs 92.6%, and 69.0% vs 98.4%.7 Additionally, Sullivan-Mee et al reported that the 313

sensitivity and specificity of the PPAA for detecting early stage glaucoma using 314

absolute differences between the overall superior and inferior macular thicknesses, 315

were 77.3% and 80.0%, respectively.18 Thus, a simple symmetry theory does not 316

necessarily satisfy both of sensitivity and specificity of the PPAA analysis. However, 317

modifying the asymmetry analyses using the PAD should be considered. 318

319

Adjusting for the asymmetrical using the PAD is an interesting possibility. However, 320

a line drawn through the middle of the thickest inferior and superior arcuate RNFL 321

bundle does not pass through the fovea. At present, we do not have a good 322

method to adjust for the asymmetry using the PAD, but it will be an important issue 323

in our future study. 324

325

This study has several limitations. First, the study was not a population-based study. 326

Epidemiological studies have shown that the Japanese population is one of the most 327

myopic groups,19 and the present study group was university students who are 328

known to be myopic. Thus, our results describe the characteristics of young myopic 329

eyes, but might not necessarily hold for older and non-myopic populations. On the 330

other hand, the reliability of the examination is very high because no pathological 331


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factors such as cataract or vitreal opacities were present in the young healthy 332

individuals and the understanding of the examination procedures was high. 333

Furthermore, the narrow range of age prevented the study from interference of the 334

cohort effects and the age effects. A second limitation was that segmentation 335

errors were found in cell number 32 (lateral of optic disc) in 20 eyes out of 64 eyes. 336

Most of these eyes had an optic disc conus. Therefore, the reliability of the 337

measurements of retinal thickness were not good for this cell. However, there were 338

few segmentation errors for other cells. The third limitation of this study was that 339

the circular scan was not adjusted for ocular magnification. According to studies on 340

scan circle size and RNFL thickness,20,21 this may have introduced some errors in 341

the mean RNFL thickness profiles and the mean angles of maximums determined. 342

However, considering the extension of the peripapillary retinal nerve fibers, the 343

angles of peak thicknesses seem to be less affected by ocular magnification. To 344

the best of our knowledge, this is the first study to investigate the symmetry between 345

the RT of corresponding cells by PPAA. However, additional studies with a larger 346

sample size and broad range of ages are needed to determine whether there are 347

patterns in the symmetry between individuals corresponding to the upper and lower 348

RT of the 64 cells. 349

350

In summary, we found by PPAA that the symmetry of the RT between corresponding 351

upper and lower cells was high in the central and temporal macular areas, but not so 352

high in the peripheral and nasal-macular area. The structural asymmetry of 353

superior and inferior RNFL bundles of the nasal macular area would break the 354

symmetry of the RT across the macula-disc axis. This information would be 355

important for interpreting the PPAA for diagnosing early glaucoma. 356

357


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2013;54:7478-7482. 395

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precision of retinal nerve fiber layer and macular thickness asymmetry parameters 408

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population: the Tajimi study. Ophthalmology. 2008;115:363-370. 412

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profile in normal eyes using third-generation optical coherence tomography. Eye. 414

2006;20:431–439. 415

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tomography high-density scanning. Invest Ophthalmol Vis Sci. 2007;48:3154–3160. 418

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page 20

FIGURE LEGENDS 420

421

Figure 1. The numbering of the 64 cells of the posterior pole asymmetry analysis. 422

423

Figure 2. Measurement of the angle between the supra- and infra-peak retinal nerve 424

fiber layer thickness. 425

426

Figure 3. Differences of retinal thickness between corresponding upper and lower 427

32 pairs of sectors. 428

429

Figure 4. Correlation coefficients of each pair are shown in the upper cells. The 430

gray tone also indicates the value of each cell as on the right scale bar. The 431

correlation coefficient equal to or lower than 0.7 are shown in white. T: temporal, F: 432

fovea, N: nasal. 433

434

Figure 5. A: and B: Grid of 64 cells superimposed on fundus photographs. The 435

thickness of each cell is designated numerically and also color-coded. The fovea-436

disc axis is shown by the slanted green-blue line. The supra temporal and infra 437

temporal peak retinal nerve fiber layer (RNFL) position are shown by the yellow dots. 438

Supra and infra peak RNFL angles are shown by yellow two-way arrows. C: and D: 439

Hemisphere asymmetry analysis obtained by posterior pole asymmetry analysis. E: 440

and F: The supra temporal and infra temporal peak RNFL positions are shown by the 441

black lines and the fovea-disc axis is shown by the blue line in the RNFL profile. 442

The sites of the angles of the supra temporal and infra temporal peak thickness of 443

the RNFL against the fovea-disc axis were approximately the same for case shown 444


21

in A, C, and E and different for case shown in B, D, and F. 445

446


page 22

SUPPLEMENTARY MATERIALS 447

448

Supplementary Table S1 449

Partial correlation coefficient between corresponding upper and lower cells retinal thickness (excluding the effect of the axial length)

Corresponding cell number

R p value

1 0.71 <0.001 2 0.73 <0.001 3 0.71 <0.001 4 0.65 <0.001 5 0.67 <0.001 6 0.66 <0.001 7 0.58 <0.001 8 0.30 0.02 9 0.71 <0.001 10 0.69 <0.001 11 0.76 <0.001 12 0.82 <0.001 13 0.81 <0.001 14 0.79 <0.001 15 0.70 <0.001 16 0.64 <0.001 17 0.77 <0.001 18 0.84 <0.001 19 0.83 <0.001 20 0.87 <0.001 21 0.85 <0.001 22 0.84 <0.001 23 0.82 <0.001 24 0.72 <0.001 25 0.94 <0.001 26 0.96 <0.001 27 0.97 <0.001 28 0.77 <0.001 29 0.86 <0.001 30 0.96 <0.001 31 0.93 <0.001 32 0.81 <0.001

450

451


23

452 Supplementary Table S2 453

Spearman's correlation coefficient between artery or vein angle difference and difference between corresponding upper and lower cells retinal thickness.


Artery angle difference vs paired cells retinal thickness

difference

Vein angle difference vs paired cells retinal thickness

difference

R p value R p value

1 0.23 0.08 0.07 0.59

2 0.19 0.13 0.10 0.45 3 0.02 0.86 0.07 0.60 4 -0.02 0.90 -0.03 0.81 5 -0.07 0.58 -0.03 0.84 6 -0.01 0.96 0.07 0.57 7 0.33 <0.01* 0.15 0.25 8 0.30 0.02* 0.14 0.29 9 0.07 0.61 0.04 0.75 10 0.16 0.23 0.03 0.85 11 0.13 0.31 -0.02 0.86 12 0.07 0.59 0.08 0.54 13 0.13 0.30 0.18 0.16 14 0.07 0.57 0.15 0.23 15 0.04 0.78 0.10 0.42 16 0.34 <0.01* 0.14 0.29 17 0.09 0.48 0.13 0.33 18 0.09 0.50 0.18 0.17 19 0.15 0.24 0.06 0.63 20 0.16 0.20 0.11 0.39 21 0.29 0.02* 0.11 0.07 22 0.26 0.04* 0.23 0.06 23 0.13 0.32 0.24 0.73 24 -0.12 0.38 0.05 0.07 25 -0.05 0.71 0.04 0.78 26 0.01 0.96 0.07 0.57 27 0.01 0.92 0.07 0.58 28 -0.23 0.08 0.10 0.44 29 -0.09 0.51 0.14 0.26 30 0.20 0.12 0.22 0.09 31 -0.01 0.99 0.27 0.03* 32 -0.23 0.08 -0.12 0.34

*:significant correlation (p < 0.05) 454


page 24

Supplementary Table S3 455

Spearman's correlation coefficient between fovea-disc angle and difference between corresponding upper and lower cells retinal thickness.


R p value

1 0.23 0.08

2 0.28 0.02* 3 0.19 0.13 4 0.19 0.13 5 0.12 0.34 6 0.15 0.25 7 0.27 0.03* 8 0.26 0.04* 9 0.03 0.79 10 0.09 0.48 11 0.04 0.77 12 0.10 0.43 13 0.26 0.04* 14 0.31 0.01* 15 0.28 0.03* 16 0.38 <0.01* 17 0.08 0.53 18 0.14 0.27 19 0.09 0.48 20 0.16 0.20 21 0.23 0.07 22 0.38 <0.01* 23 0.42 <0.01* 24 0.24 0.07 25 0.05 0.71 26 -0.02 0.87 27 0.05 0.70 28 0.08 0.55 29 0.06 0.63 30 0.21 0.10 31 0.11 0.37 32 -0.17 0.20

*:significant correlation (p < 0.05) 456

457

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Posterior Pole Asymmetry Analyses of Retinal Thickness of Upper and Lower Sectors and Their...

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