Glaucoma is characterized by chronic progressive optic neuropathy with corresponding and characteristic patterns of visual field (VF) defects. Mikelberg and Drance found that 70% glaucomatous eyes had initial damage limited to a single hemifield and 57% still had only a single hemifield defect at the completion of follow-up [
This study was approved by the Ethics Committee of Toho University Ohashi Medical Center (number H17036), and all study conducts adhered to the tenets of the Declaration of Helsinki. We retrospectively reviewed the medical records of patients with glaucoma from the Department of Ophthalmology Outpatient Clinic at Toho University Ohashi Medical Center (Tokyo, Japan) between July 2007 and August 2017. The inclusion criteria were (1) clinical diagnosis of untreated POAG or NTG with a hemifield defect, (2) OCT measurements such as macular ganglion cell complex (mGCC) and circumpapillary retinal nerve fiber layer (cpRNFL) thicknesses corresponding to defective hemifields showing significant (
All patients underwent OCT measurements of both mGCC and cpRNFL thicknesses within 6 months of the Humphrey field analyzer (HFA; Carl Zeiss Meditec Inc., Dublin, CA, USA) measurements. In all patients, we recorded age, sex, visual acuity, spherical equivalent refractive error, untreated IOP, central corneal thickness (CCT), OCT disc area, disc hemorrhage (DH) during follow-up, family history of glaucoma, history of systemic hypertension and diabetes mellitus, and mean deviation (MD), and pattern standard deviation (PSD) in the standard automated perimetry with the HFA. The IOP was measured with a Goldmann applanation tonometer, and the mean untreated IOP was calculated by three measurement values obtained on 3 separate days. If the IOP measurement exceeded 21 mmHg even once, we diagnosed the patient with POAG [
All OCT measurements were performed with the RTVue-100 Spectral-domain OCT (software version 4.0, Optovue, Inc., Fremont, CA, USA), which uses a scanning laser diode to emit a scan beam with a wavelength of 840 ± 10 nm. This system provides images of ocular microstructures.
In this study, the GCC scanning protocol was used to measure mGCC thickness. The GCC protocol consists of one horizontal and 15 vertical line scans that cover a 7 × 7 mm region. Each GCC scan captures 15,000 data points within 0.6 seconds, and a 6 × 6 mm map (corresponding to approximately 20° on the visual field map) is created. The mGCC thickness was measured from the internal limiting membrane to the outer inner plexiform layer boundary, and the OCT system provided overall superior and inferior hemifield averages.
The optic nerve head (ONH) protocol was used for cpRNFL thickness measurements. Using the fundus picture generated by OCT (a video baseline protocol), we manually traced ONH contours. The RNFL thickness was automatically measured along a 3.45 mm-diameter circle centered at the center of the optic disc. A total of 775 A-scans was obtained along this circle. We obtained the average thickness of cpRNFL in the superior and inferior hemifields, and the superior-temporal (ST), temporal-upper (TU), temporal-lower (TL), and inferior-temporal (IT) average thicknesses of cpRNFL, which were measured automatically by OCT. In addition, the disc area was obtained from disc parameters (Figure
(a) A representative eye with glaucoma with superior hemifield defects measured by spectral-domain optical coherence tomography (SDOCT). Circumpapillary retinal nerve fiber layer (cpRNFL) thickness map (left) and macular ganglion cell complex (mGCC) thickness map (right). ST: superior-temporal; TU: temporal-upper; TL: temporal-lower; IT: inferior-temporal; IN: inferior-nasal; NL: nasal-lower; NU: nasal-upper; SN: superior-nasal. (b) Evaluation of the central visual field defect. The VF defects correspond to the cpRNFL and mGCC maps at the top panels. In the pattern deviation plot of the visual field measured by the Humphrey field analyzer, the prevalence of significant (
A trained operator obtained good quality OCT images from each subject after pupillary dilation. Images were excluded from analyses when the signal strength index was low (<40), when segmentation errors occurred, or when the scan circle was not centered at the optic disc.
Standard automated perimetry was performed with the HFA using the 30-2 Swedish Interactive Threshold Algorithm. VF tests were considered reliable when fixation losses were <20%, false positives were <15%, and false negatives were <25%. A glaucomatous functional hemifield defect was defined by the presence of three or more significant (
In the pattern deviation plot of the HFA, we examined for the presence of significant (
Data are reported as mean ± standard deviation. The normality of the data was examined using the Shapiro–Wilk test, and nonparametric tests were performed for nonnormally distributed data. Average TD values for the superior or inferior hemifield were calculated. Age, spherical equivalent refractive error, untreated IOP, CCT, disc area, MD, PSD, averages of superior mGCC and cpRNFL thicknesses corresponding to the inferior VF defect, averages of inferior mGCC and cpRNFL thicknesses corresponding to the superior VF defect, average TD values for the superior and inferior hemifields, C8-sup and -inf, and C2-sup and -inf corresponding to the superior or inferior hemifield defect between the two groups were compared using the Mann–Whitney
From the chart review, 106 patients who had hemifield defect consistent with the VF criteria were located. Among them, 67 eyes of 67 patients met the hemisphere disorder criteria of OCT corresponding to the VF defect.
The subjects’ characteristics are presented in Table
Patient characteristics.
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Age (years) | 56.15 ± 11.73 |
Sex: male/female | 24 (35.8%)/43 (64.2%) |
Family history of glaucoma: yes/no | 14 (20.9%)/53 (79.1%) |
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POAG/NTG | 5 (7.5%)/62 (92.5%) |
Visual acuity | 1.19 ± 0.05 |
Spherical equivalent (D) | −2.65 ± 2.53 |
Untreated IOP (mmHg) | 15.20 ± 2.26 |
CCT ( |
526.28 ± 33.98 |
DH: presence/absence | 3 (4.5%)/64 (95.5%) |
Disc area (mm2) | 2.04 ± 0.44 |
cpRNFL thickness corresponding to defective hemifield ( |
77.10 ± 10.06 |
mGCC thickness corresponding to defective hemifield ( |
78.04 ± 8.67 |
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MD (dB) | −2.80 ± 3.12 |
PSD (dB) | 6.52 ± 4.25 |
Average TD values corresponding to defective hemifield (dB) | −5.31 ± 6.07 |
Prevalence of defects within 10 degrees: yes/no | 62 (92.5%)/5 (7.5%) |
Prevalence of defects within 5 degrees: yes/no | 26 (38.8%)/41 (61.2%) |
Average TD values of superior within 10 degrees (C8-sup) (dB) | −4.92 ± 7.67 |
Average TD values of inferior within 10 degrees (C8-inf) (dB) | −1.51 ± 3.75 |
Average TD values of superior within 5 degrees (C2-sup) (dB) | −3.71 ± 8.35 |
Average TD values of inferior within 5 degrees (C2-inf) (dB) | 0.02 ± 1.89 |
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Hypertension: yes/no | 15 (22.4%)/52 (77.6%) |
Diabetes mellitus: yes/no | 7 (10.4%)/60 (89.6%) |
Continuous variables are expressed as
Comparison of clinical characteristics between the superior hemifield and inferior hemifield defect groups.
Superior visual field defect group | Inferior visual field defect group |
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Age (years) | 54.33 ± 13.31 | 58.85 ± 8.39 | 0.205 |
Sex: male/female | 15 (37.5%)/25 (62.5%) | 9 (33.3%)/18 (66.7%) | 0.727 |
Family history of glaucoma: yes/no | 9 (22.5%)/31 (77.5%) | 5 (18.5%)/22 (81.5%) | 0.694 |
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Visual acuity | 1.18 ± 0.06 | 1.19 ± 0.04 | 0.340 |
Spherical equivalent (D) | −2.50 ± 2.78 | −2.87 ± 2.15 | 0.711 |
Untreated IOP (mmHg) | 15.57 ± 2.40 | 14.66 ± 1.97 | 0.107 |
CCT ( |
524.13 ± 33.75 | 529.48 ± 34.70 | 0.385 |
DH: presence/absence | 1 (7.5%)/39 (92.5%) | 2 (7.4%)/25 (92.6%) | 0.354 |
Disc area (mm2) | 2.07 ± 0.45 | 2.00 ± 0.42 | 0.544 |
cpRNFL thickness corresponding to the defective hemifield ( |
75.27 ± 8.02 | 79.83 ± 12.14 | 0.050 |
mGCC thickness corresponding to the defective hemifield ( |
75.86 ± 9.44 | 81.27 ± 6.25 |
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MD (dB) | −3.30 ± 3.72 | −2.07 ± 1.73 | 0.609 |
PSD (dB) | 6.94 ± 4.81 | 5.90 ± 3.24 | 0.596 |
Average TD values corresponding to defective hemifield (dB) | −6.51 ± 7.34 | −3.53 ± 2.53 | 0.371 |
Prevalence of defects within 10 degrees: yes/no | 39 (97.5%)/1 (2.5%) | 23 (85.2%)/4 (14.8%) | 0.081 |
Prevalence of defects within 5 degrees: yes/no | 22 (55.0%)/18 (45.0%) | 4 (14.8%)/23 (85.2%) |
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Average TD values within 10 degrees corresponding to defective hemifield (C8) (dB) | −8.02 ± 8.55 | −3.93 ± 4.99 | 0.066 |
Average TD values within 5 degrees corresponding to defective hemifield (C2) (dB) | −6.09 ± 9.37 | −1.00 ± 5.16 |
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Hypertension: yes/no | 8 (20.0%)/32 (80.0%) | 7 (25.9%)/20 (74.1%) | 0.568 |
Diabetes mellitus: yes/no | 4 (10.0%)/36 (90.0%) | 3 (11.1%)/24 (88.9%) | 0.594 |
Continuous variables are expressed as
There was no significant difference in the prevalence of “defects within 10 degrees” between the two groups. However, the superior VF defect group had a higher prevalence of “defects within 5 degrees” (
The average TD of the superior and inferior VF defect was similar between the groups. There was no significant difference between the C8-sup corresponding to the defective hemifields of the superior VF defect group and the C8-inf corresponding to the defective hemifields of the inferior VF defect group. However, the C2-sup corresponding to the defective hemifields of the superior VF defect group was significantly lower than C2-inf corresponding to the defective hemifields of the inferior VF defect group (
For the inferior mGCC thickness in the superior VF defect group, ST, TU, TL and IT RNFL thickness, and C2-sup were selected as significant related factors by univariate regression analysis. In multivariate analysis, ST, TU, TL and IT RNFL thickness, and C2-sup were included as explanatory variables; the TL RNFL thickness (slope = 0.47
Univariate and multivariate regression analyses for inferior mGCC thickness in the superior visual field defect group.
Univariate regression analysis | Multivariate regression analysis | |||||
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Slope |
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95% CI |
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Age | 0.03 | 0.850 | ||||
Sex | 0.10 | 0.581 | ||||
Family history of glaucoma | 0.18 | 0.277 | ||||
Visual acuity | 0.05 | 0.768 | ||||
Spherical equivalent (D) | 0.09 | 0.564 | ||||
Untreated IOP (mmHg) | 0.10 | 0.542 | ||||
CCT ( |
0.18 | 0.281 | ||||
DH | 0.01 | 0.973 | ||||
Disc area (mm2) | 0.12 | 0.474 | ||||
ST RNFL thickness ( |
0.22 |
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TU RNFL thickness ( |
0.32 |
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TL RNFL thickness ( |
0.66 |
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0.47 | 0.545 | 0.25, 0.70 |
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IT RNFL thickness ( |
0.50 |
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0.16 | 0.27 | 0.01, 0.31 |
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C2-sup (dB) | 0.45 |
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C2-inf (dB) | 0.09 | 0.597 | ||||
Hypertension | 0.20 | 0.223 | ||||
Diabetes mellitus | 0.11 | 0.485 |
CCT: central corneal thickness, DH: disc hemorrhage, ST: superior-temporal, TU: temporal-upper, TL: temporal-lower, IT: inferior-temporal, RNFL: retinal nerve fiber layer, C2-sup: average total deviation (TD) values of superior 2 points within central 5 degrees, r: correlation coefficient,
Univariate and multivariate regression analyses for superior mGCC thickness in the inferior visual field defect group.
Univariate regression analysis | Multivariate regression analysis | |||||
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Slope |
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95% CI |
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Age | 0.11 | 0.588 | ||||
Sex | 0.17 | 0.400 | ||||
Family history of glaucoma | 0.31 |
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5.93 | 0.38 | 2.00, 9.85 |
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Visual acuity | 0.04 | 0.836 | ||||
Spherical equivalent (D) | 0.47 |
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Untreated IOP (mmHg) | 0.19 | 0.354 | ||||
CCT ( |
0.20 | 0.317 | ||||
DH | 0.19 | 0.343 | ||||
Disc area (mm2) | 0.40 |
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5.15 | 0.35 | 1.43, 8.87 |
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ST RNFL thickness ( |
0.56 |
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TU RNFL thickness ( |
0.65 |
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0.41 | 0.64 | 0.25, 0.56 |
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TL RNFL thickness ( |
0.01 | 0.625 | ||||
IT RNFL thickness ( |
0.06 | 0.767 | ||||
C2-sup (dB) | 0.30 |
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C2-inf (dB) | 0.24 | 0.227 | ||||
Hypertension | 0.13 | 0.527 | ||||
Diabetes mellitus | 0.07 | 0.718 |
CCT: central corneal thickness, DH: disc hemorrhage, ST: superior-temporal, TU: temporal-upper, TL: temporal-lower, IT: inferior-temporal, RNFL: retinal nerve fiber layer, C2-sup: average total deviation (TD) values of superior 2 points within central 5 degrees, r: correlation coefficient,
In this study, we investigated factors related to superior and inferior hemifield defects in patients with POAG or NTG. Since structural damages have been reported [
We found that central VF damage was more frequent and severe in the superior VF defect group than in the inferior VF defect group, and the C2-sup corresponding to the defective hemifields of the superior VF defect group was significantly lower than C2-inf corresponding to the defective hemifields of the inferior VF defect group, although the average TD of the superior and inferior hemifield defects was similar between the groups (Table
Previously, Hood et al. [
To investigate factors related to the thickness of mGCC, which closely influences parafoveal scotoma, we performed multivariate regression analysis. We found that TL RNFL thickness and IT RNFL thickness were significant contributing factors to the corresponding inferior mGCC thickness in 40 eyes with the superior VF defect group (Table
Our novel finding is that the optic disc area was a contributing factor to superior mGCC thickness in the inferior VF defect group (Table
We also found that the prevalence of “defects within 5 degrees” was higher in the superior VF defect group than in the inferior VF defect group, although there was no significant difference in the prevalence of “defects within 10 degrees” between the two groups. The average TD of the superior and inferior hemifield defects in the two groups was similar (Table
Mikelberg et al. [
Although we excluded patients with high myopia (over −6.00) from the study, we did not find any difference in the degree of myopia between the superior and inferior VF defect groups. Similarly, findings have been reported by previous studies evaluating differences between patients with initial parafoveal and initial peripheral scotoma [
There was no difference in age, sex, and CCT between the two groups (Table
Previous studies have reported that patients with POAG with diabetes mellitus showed higher prevalence of inferior VF defect [
Previous studies have found a higher prevalence of systemic hypertension in patients with superior peripheral scotoma than in those with superior parafoveal scotoma [
Patients with POAG with high-pretreatment IOP (>21 mmHg) develop parafoveal scotomas more frequently than peripheral scotomas [
DH is a well-known, definite risk factor for the progression of glaucoma [
This study has some limitation including a retrospective design. We assessed the prevalence of systemic risk factors based on patient recall. Although eyes with high myopia (over −6.00 D) were excluded from the study, we did not measure axial length, optic disc tilt, or torsion. Future studies are needed to clarify the influence of these factors in glaucomatous eyes with myopia.
We investigated the factors related to superior or inferior hemifield defects in POAG. The definitions of hemifield defects were based on both VF results and OCT measurements. We found that there was no significant difference regarding cpRNFL thickness corresponding to the superior or inferior defective hemisphere. However, the inferior mGCC thickness corresponding to the superior VF defect group was significantly thinner than the superior mGCC thickness corresponding to the inferior VF defect group. Although the average TD of the superior and inferior VF defects was similar between the groups, paracentral VF damage may be more frequent and severe in the superior VF defect group than in the inferior VF defect group. In this study, we found for the first time that the disc area was related to superior mGCC thickness in the inferior VF defect group, and this suggests that the factors related to the reduction of the corresponding mGCC thickness may differ between superior VF defect and inferior VF defect groups.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
The authors deeply thank Mr. Takashi Sato, their photographer, for data acquisition of the OCT measurements.