In our main analysis, data from 79 glaucomatous and 149 normal subjects met the inclusion criteria. Patients with glaucoma were older than control subjects (mean ± 1 SD = 56.0 ± 13.9 years in the glaucoma group and 40.3 ± 11.3 years in the control group; P < 0.001). For this reason, age-adjusted aROCs were used in comparing the imaging techniques and subjective assessment. In addition, patients and control subjects with African ancestry and female gender predominated in both study groups (African-American in the glaucoma group, 46 [58.2%], and in the control group, 82 [55.0%]); women in the glaucoma group, 54 [68.4%], and in the control group, 111 [74.5%]). However, univariate analysis showed no race or gender differences between the control and glaucoma groups (P = 0.67 and 0.35, respectively). There was a difference in spherical refraction between the two study groups (−0.4 ± 1.9 D in the glaucoma group, −1.1 ± 1.5 D in the control group; P = 0.0074). The difference in cylindrical refraction was of borderline significance (0.6 ± 0.7 D, glaucoma group; 0.4 ± 0.6 D, control group; P = 0.040). However, regression analysis showed no evidence that refraction state (sphere, cylinder, or spherical equivalent) was significantly associated with any of the imaging parameters. Refraction was not included in any further analysis. No differences were found in optic disc area between glaucoma and control group (disc area with HRT II for glaucoma group = 2.5 ± 0.5 mm2, for control group = 2.2 ± 0.5 mm2, P = 0.082; disc area with StratusOCT for glaucoma group = 2.5 ± 0.5 mm2, for control group 2.4 ± 0.4 mm2, P = 0.12).
The glaucoma group had an average mean deviation (MD ± SD) of −3.8 ± 3.6 dB and control group had an average MD of 0.2 ± 1.0 dB. Furthermore, 44 (55.7%) eyes had an early defect, 31 (39.2%) eyes had a moderate defect, and 4 (5.1%) eyes had a severe defect, according to the classification of severity of field loss by Hodapp et al..
26 Thus, the cohort with glaucomatous eyes predominantly had early to moderate visual field defects.
The stereophotograph grading obtained from the 15-point likelihood score scale fell within a range of 3 to 10 for the control group (mean 5.2 ± 1.9 SD) and 75% of control eyes received a score from 3 to 6. In the glaucoma group, the range of score was from 3 to 15 (mean, 10.6 ± 3.7 SD) and 70% of glaucomatous eyes received a score from 9 to 15. The mean of scores significantly differed between the two study groups (P < 0.0001). The 15-point likelihood score for stereophotograph grading had an overall sensitivity of 77.2% fixed at ≥80.0% specificity (aROC = 0.903; SE = 0.03), adjusted for age.
Significant differences were found between control and glaucomatous eyes in GDx VCC, HRT II, and StratusOCT measurements (
Table 1GDx VCC,
Table 2global HRT II, and
Table 3StratusOCT). Also shown are the aROC and sensitivities at fixed specificity of at least 80%. Data for sectoral HRT II parameters are not shown because of space limitations. To compare diagnostic methods, we selected the parameter with the largest aROC from each technique. For GDx, the NFI showed the largest aROC (0.836). For the HRT II, the best global parameter was cup-to-disc area ratio, with an aROC of 0.861 and the best sectoral HRT II parameter was temporal inferior cup volume with a comparable aROC (0.854). For the StratusOCT, the ONH analysis parameter with the largest aROC was the vertical integrated rim area (0.854). Similarly, the RNFL thickness at the inferior quadrant (6:00 sector) had the largest aROC (0.844). Last, for the macular thickness, the largest aROC was obtained from thickness at the superior outer macular location (0.815).
Figure 1shows the age-adjusted ROC curves for each best parameter compared with stereophotograph grading. Compared with all measures, the stereophotograph grading showed the largest aROC, in both age-adjusted and crude analysis.
Table 4shows pair-wise comparisons of aROC between stereophotograph grading and each imaging technique. After Bonferroni correction, a borderline significance was found between stereophotograph grading and HRT global cup-to-disc area ratio, StratusOCT ONH (vertical integrated rim area), and StratusOCT RNFL thickness in the inferior quadrant, whereas macular thickness and GDx VCC NFI had significantly lower aROCs (
P = 0.001 and 0.007, respectively). No significant differences in aROC were found between each imaging technique, suggesting HRT II (global and sectoral), StratusOCT (ONH, RNFL, and macular thickness), and GDx VCC were equivalent in their diagnostic ability (data not shown because of space restrictions).
Agreement of dichotomous classification between stereophotographs and classification from the best parameter of each imaging technique was good between stereophotograph grading and StratusOCT vertical integrated rim area, moderate between stereophotograph grading and HRT II global cup-to-disc area ratio and GDx-VCC NFI, and fair between stereophotograph grading and StratusOCT RNFL and macular thickness. Venn diagrams
(Fig. 2)illustrate the results of disease classification by each technique. Classification based on subjective assessment of the optic disc (stereophotos) was compared against imaging techniques measuring optic disc topography
(Fig. 2A)and separately against techniques that assessed RNFL integrity
(Fig. 2B) . Subjective assessment correctly identified more patients with glaucoma than did objective methods. As demonstrated by the levels of agreement in
Table 5 , techniques that evaluated optic disc characteristics had higher levels of agreement with subjective assessment of the optic disc than did techniques that evaluated RNFL parameters. Overall, the combination of subjective assessment of the optic disc with RNFL associated parameters
(Fig. 2A)correctly identified more subjects (70/79 eyes) than did the combination of subjective disc assessment with optic disc parameters (
Fig. 2B ; 65/79 eyes).
Similar results were found in the secondary analysis using control subjects defined only by visual field tests, ignoring the information from the initial dilated fundus examination. Results are presented as age-adjusted aROC (SE, percentage of sensitivity at 80% specificity): for stereophotograph grading 0.879 (0.03, 76.25), HRT II cup-to-disc ratio 0.849 (0.03, 75.00), GDx VCC NFI 0.843 (0.03, 70.00), StratusOCT ONH VIRA 0.848 (0.03, 69.23), StratusOCT RNFL 0.836 (0.03, 69.23), and StratusOCT macular thickness 0.826 (0.03, 67.95). Stereophoto grading still provided significantly greater diagnostic efficacy that the other modalities.