Abstract
Purpose
To evaluate the usefulness of automated measurements of the localized retinal nerve fiber layer (RNFL) defects area in patients with glaucoma.
Methods
Fifty one patients with localized RNFL defects in RNFL red-free photographs and 53 healthy subjects were included. All participants were imaged with 3D spectral-domain optical coherence tomography (OCT). The area of defects was measured with the RNFL significance map (red = p < 1% and yellow = p < 5%) using Image J manually and Matlab software automatically. The area under the receiver operating characteristic curve (AUC) was calculated for the RNFL de-fect area of the RNFL photograph and RNFL maps, circumpapillary RNFL thickness, optic disc parameter, and macular in-ner retina thickness.
Results
High correlation was observed between manually and automatically measured defect areas in the significance map (red area r = 0.904, red and yellow area r = 0.890). The AUC for manually and automatically measured defects area (0.987, 0.966; p < 5%, p = 0.31, respectively) in the significance map was comparable. The latter demonstrated slightly higher but insignificant difference in AUC for inferior quadrant circumpapillary RNFL thickness (0.936; p = 0.22) and was significantly higher than the inferior ganglion cell layer plus inner plexiform layer thickness (0.894) and vertical cup to disc ratio (0.869) (p = 0.018, p = 0.008, respectively).
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Figure 1.
(A) The cSLO RNFL photographs were overlaid with a color disc photograph (5 × 5 mm2) as a reference image that was obtained by Topcon 3D OCT-2000. (B) The retinal blood vessels (arrow) and RNFL defects (arrow head) were matched between the cSLO RNFL photograph and the reference image. cSLO = confocal scanning laser ophthalmoscope; RNFL = retinal nerve fi-ber layer; OCT = optical coherence tomography; T = temporal; N = nasal.
![jkos-54-902f1.tif](/upload/SynapseXML/0035jkos/thumb/jkos-54-902f1.gif)
Figure 2.
(A) Original photograph in the retinal nerve fiber layer (RNFL) significance map, RNFL thickness map, optic disc photo-graph, and cSLO RNFL photograph. The RNFL significance map, RNFL thickness map, and optic disc photograph were obtained by Topcon 3D OCT-2000, and the RNFL photograph was captured by a Nidek F-10 cSLO. (B) Each boundary of the RNFL defects was manually delineated. The areas of the RNFL defects were measured on the 5 × 5 mm2 parapapillary area using Image J software (yellow lines) manually. Superpixels coded in red, red and yellow were automatically calculated by a Matlab computer program ac-cording to the red, green, and blue values in the 5 × 5 mm2 circumpapillary region. Measurement of the area of localized RNFL defect in the significance map (red area = 1.11 mm2, red and yellow area = 2.79 mm2), thickness map (1.40 mm2), cSLO RNFL photograph (1.77 mm2) manually, and automated measurement using significance map (red area = 0.84 mm2, red and yellow area = 3.59 mm2). cSLO = confocal scanning laser ophthalmoscope; RNFL = retinal nerve fiber layer; OCT = optical coherence tomography.
![jkos-54-902f2.tif](/upload/SynapseXML/0035jkos/thumb/jkos-54-902f2.gif)
Figure 3.
(A) Scatter plots showing the relationship of manually measured red area (p < 1%) of significance map against automati-cally measured red area (p < 1%) of significance map (r = 0.904, p < 0.001). (B) Relationship of manually measured red and yel-low area (p < 5%) of significance map against automatically measured red and yellow area (p < 5%) of significance map (r = 0.890, p < 0.001).
![jkos-54-902f3.tif](/upload/SynapseXML/0035jkos/thumb/jkos-54-902f3.gif)
Figure 4.
Bland-Altman plots of agreement between manually and automatically measured (A) red area (p < 1%) and (B) red and yellow area (p < 5%) in the significance map. Differences between automatically and manually measured areas were plotted against the means. Dash lines represent the 95% confidence intervals.
![jkos-54-902f4.tif](/upload/SynapseXML/0035jkos/thumb/jkos-54-902f4.gif)
Figure 5.
The cut-off point (>0.546 mm2), sensitivity (90.2%), and specificity (94.3%) of automated measurements of sig-nificance map red and yellow area (p < 5%).
![jkos-54-902f5.tif](/upload/SynapseXML/0035jkos/thumb/jkos-54-902f5.gif)
Figure 6.
Receiver operating characteristics curves of the man-ually measured significance map red and yellow area (p < 5%), automatically measured significance map red and yellow area (p < 5%), circumpapillary inferior quadrant retinal nerve fi-ber layer (RNFL) thickness, inferior ganglion cell layer + in-ner plexiform layer thickness (GCL + IPL thickness), and vertical cup to disc ratio (CDR).
![jkos-54-902f6.tif](/upload/SynapseXML/0035jkos/thumb/jkos-54-902f6.gif)
Table 1.
Demographics and characteristics of subjects with localized RNFL defects and normal controls
Normal eyes (n = 53) | Eyes with RNFL defects (n = 51) | p-value | |
---|---|---|---|
Age (years) | 56.3 ± 10.7 | 57.7 ± 13.7 | 0.54* |
Gender (male:female) | 28:25 | 29:22 | 0.68† |
Eye (right:left) | 24:29 | 21:30 | 0.67† |
Spherical equivalent (diopters) | -0.15 ± 1.29 | -0.65 ± 2.05 | 0.15* |
Central corneal thickness (μ m) | 543.78 ± 32.17 | 539.33 ± 31.98 | 0.50* |
Mean deviation (dB) | -1.45 ± 0.91 | -6.15 ± 4.33 | <0.001* |
Pattern standard deviation (dB) | 1.58 ± 0.69 | 6.08 ± 4.20 | <0.001* |
Type of glaucoma | NA | ||
Preperimetric | 7 | ||
Perimetric | 44 | ||
Localized RNFL defects | NA | 64 | |
Superior | 11 | ||
Inferior | 27 | ||
Superior and inferior | 13 |
Table 2.
Area under the receiver operating characteristic curves (AUCs) of the red-free photograph, thickness map, and significance map between normal controls and eyes with RNFL defects
Normal (n = 53) | Eyes with RNFL defects (n = 51) | p-value* | AUCs (95% CI) | Sn/Sp (Sp ≥ 80%) | Sn/Sp (Sp ≥ 90%) | |
---|---|---|---|---|---|---|
Defect area (mm2) | ||||||
Photographic (manual) | 0 | 2.41 ± 1.46 | <0.001 | 1.000 (1.000-1.000) | NA | 100/100 |
Thickness map (manual) | 0 | 2.04 ± 1.35 | <0.001 | 1.000 (1.000-1.000) | NA | 100/100 |
Significance map red (manual) | 0 | 1.65 ± 1.17 | <0.001 | 0.961 (0.924-0.998) | NA | 92/100 |
Significance map red & yellow (manual) | 0.01 ± 0.10 | 2.77 ± 1.83 | <0.001 | 0.987 (0.967-1.000) | NA | 98/98 |
Significance map red (automatic) | 0.01 ± 0.04 | 1.70 ± 1.43 | <0.001 | 0.963 (0.925-1.000) | 94/85 | 94/92 |
Significance map red & yellow (automatic) | 0.16 ± 0.32 | 3.15 ± 2.25 | <0.001 | 0.966 (0.932-1.000) | 98/83 | 90/94 |
Table 3.
Area under the receiver operating characteristic curves (AUCs) of circumpapillary RNFL thickness between normal con-trols and eyes with RNFL defects
Normal (n = 53) | Eyes with RNFL defects (n = 51) | p-value* | AUCs (95% CI) | Sn/Sp (Sp ≥ 80%) | Sn/Sp (Sp ≥ 90%) | |
---|---|---|---|---|---|---|
Circumpapillary RNF | FL thickness (μ m) | |||||
Average | 104.2 ± 8.1 | 83.3 ± 12.8 | <0.001 | 0.917 (0.864-0.970) | 78/81 | 76/92 |
Quadrant | ||||||
Temporal | 79.2 ± 10.6 | 69.3 ± 12.2 | <0.001 | 0.726 (0.628-0.823) | 55/81 | 35/91 |
Superior | 122.7 ± 12.6 | 101.7 ± 18.3 | <0.001 | 0.863 (0.791-0.935) | 80/85 | 67/91 |
Nasal | 84.7 ± 14.4 | 74.5 ± 15.8 | 0.001 | 0.710 (0.608-0.811) | 51/81 | 39/91 |
Inferior | 129.2 ± 10.8 | 90.3 ± 22.2 | <0.001 | 0.936 (0.890-0.981) | 88/81 | 82/91 |
Clock-hour | ||||||
9 (temporal) | 68.0 ± 10.9 | 64.3 ± 12.6 | 0.12 | 0.602 (0.492-0.713) | 35/81 | 24/91 |
10 | 91.2 ± 12.8 | 77.1 ± 19.4 | <0.001 | 0.719 (0.618-0.820) | 57/81 | 47/91 |
11 | 127.2 ± 17.5 | 99.6 ± 29.2 | <0.001 | 0.786 (0.695-0.877) | 65/81 | 61/91 |
12 (superior) | 122.6 ± 18.2 | 103.3 ± 22.9 | <0.001 | 0.771 (0.680-0.862) | 51/81 | 39/92 |
1 | 122.0 ± 15.2 | 102.3 ± 19.3 | <0.001 | 0.795 (0.709-0.881) | 65/81 | 49/91 |
2 | 99.1 ± 16.2 | 85.3 ± 20.5 | <0.001 | 0.718 (0.617-0.819) | 61/81 | 33/92 |
3 (nasal) | 74.4 ± 15.5 | 66.4 ± 15.3 | 0.009 | 0.667 (0.562-0.773) | 41/81 | 20/92 |
4 | 80.3 ± 18.2 | 71.6 ± 19.6 | 0.02 | 0.644 (0.537-0.751) | 41/81 | 20/91 |
5 | 114.1 ± 16.5 | 95.3 ± 20.5 | <0.001 | 0.767 (0.674-0.861) | 67/83 | 41/91 |
6 (inferior) | 134.4 ± 17.5 | 93.4 ± 25.7 | <0.001 | 0.896 (0.836-0.957) | 80/83 | 75/91 |
7 | 138.7 ± 17.5 | 82.0 ± 34.6 | <0.001 | 0.907 (0.845-0.970) | 84/85 | 82/94 |
8 | 78.3 ± 12.9 | 66.6 ± 16.2 | <0.001 | 0.736 (0.637-0.835) | 63/81 | 49/92 |
Table 4.
Area under the receiver operating characteristic curves (AUCs) of macular inner retina thickness and optic disc parameter between normal controls and eyes with RNFL defects
Normal (n = 53) | Eyes with RNFL defects (n = 51) | p-value* | AUCs (95% CI) | Sn/Sp (Sp ≥ 80%) | Sn/Sp (Sp ≥ 90%) | |
---|---|---|---|---|---|---|
Macular inner retina thick | kness (μ m) | |||||
NFL | ||||||
Superior | 34.1 ± 4.9 | 29.6 ± 7.5 | <0.001 | 0.719 (0.616-0.822) | 59/81 | 39/92 |
Inferior | 37.6 ± 4.2 | 24.3 ± 10.5 | <0.001 | 0.859 (0.778-0.941) | 75/83 | 73/92 |
Total | 35.8 ± 4.0 | 26.9 ± 7.6 | <0.001 | 0.846 (0.762-0.930) | 78/83 | 73/94 |
GCL + IPL | ||||||
Superior | 72.1 ± 5.7 | 65.9 ± 5.5 | <0.001 | 0.789 (0.702-0.876) | 51/85 | 39/94 |
Inferior | 70.5 ± 5.9 | 60.4 ± 6.2 | <0.001 | 0.894 (0.832-0.956) | 75/85 | 71/91 |
Total | 71.3 ± 4.8 | 63.2 ± 5.0 | <0.001 | 0.879 (0.815-0.943) | 65/83 | 59/94 |
GCC | ||||||
Superior | 106.2 ± 7.8 | 95.5 ± 12.0 | <0.001 | 0.770 (0.678-0.863) | 61/83 | 39/91 |
Inferior | 108.0 ± 8.3 | 84.6 ± 15.6 | <0.001 | 0.893 (0.829-0.958) | 82/81 | 73/91 |
Total | 107.2 ± 7.8 | 90.1 ± 11.9 | <0.001 | 0.875 (0.806-0.943) | 82/81 | 67/92 |
Optic nerve head | ||||||
Cup area (mm2) | 1.06 ± 0.50 | 1.61 ± 0.68 | <0.001 | 0.732 (0.636-0.828) | 47/83 | 43/91 |
Rim area (mm2) | 2.01 ± 0.47 | 1.24 ± 0.52 | <0.001 | 0.869 (0.796-0.941) | 84/85 | 65/91 |
C/D area ratio | 0.34 ± 0.14 | 0.56 ± 0.17 | <0.001 | 0.827 (0.747-0.907) | 69/81 | 63/91 |
Linear CDR | 0.57 ± 0.14 | 0.74 ± 0.13 | <0.001 | 0.824 (0.744-0.905) | 69/81 | 61/91 |
Vertical CDR | 0.58 ± 0.13 | 0.79 ± 0.14 | <0.001 | 0.869 (0.798-0.940) | NA | 73/91 |
Cup volume (mm3) | 0.24 ± 0.18 | 0.35 ± 0.25 | 0.01 | 0.628 (0.520-0.736) | 43/81 | 18/91 |
Rim volume (mm3) | 0.17 ± 0.19 | 0.15 ± 0.17 | 0.56 | 0.562 (0.448-0.675) | 37/83 | 22/91 |
Table 5.
Comparison of significance map area analyzed by manual and automatic method
Manual | Automatic | Difference | p-value* | r | p-value† | |
---|---|---|---|---|---|---|
Significance map red area (mm2) | 0.81 ± 1.16 | 0.84 ± 1.31 | -0.03 ± 0.56 | 0.54 | 0.904 | <0.001 |
Significance map red and yellow area (mm2) | 1.38 ± 1.89 | 1.64 ± 2.19 | -0.26 ± 1.00 | 0.009 | 0.890 | <0.001 |
Table 6.
Relationships (correlation coefficients) between retinal nerve fiber layer defect areas and structural-functional p parameters
Table 7.
Probability values for the differences (upper triangle of numbers) between area under the receiver operating characteristic curves