February 2011
Volume 52, Issue 2
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Glaucoma  |   February 2011
Predictors of Normal Optic Nerve Head, Retinal Nerve Fiber Layer, and Macular Parameters Measured by Spectral Domain Optical Coherence Tomography
Author Affiliations & Notes
  • Harsha L. Rao
    From the VST Glaucoma Center and
    the Center for Clinical Epidemiology and Biostatistics, L. V. Prasad Eye Institute, Hyderabad, India.
  • Addepalli U. Kumar
    From the VST Glaucoma Center and
  • Jonnadula G. Babu
    From the VST Glaucoma Center and
  • Anjul Kumar
    From the VST Glaucoma Center and
  • Sirisha Senthil
    From the VST Glaucoma Center and
  • Chandra S. Garudadri
    From the VST Glaucoma Center and
  • Corresponding author: Harsha L. Rao, L. V. Prasad Eye Institute, Banjara Hills, Hyderabad, 500034, India; harshabl.76@gmail.com
Investigative Ophthalmology & Visual Science February 2011, Vol.52, 1103-1110. doi:10.1167/iovs.10-5997
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      Harsha L. Rao, Addepalli U. Kumar, Jonnadula G. Babu, Anjul Kumar, Sirisha Senthil, Chandra S. Garudadri; Predictors of Normal Optic Nerve Head, Retinal Nerve Fiber Layer, and Macular Parameters Measured by Spectral Domain Optical Coherence Tomography. Invest. Ophthalmol. Vis. Sci. 2011;52(2):1103-1110. doi: 10.1167/iovs.10-5997.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: To evaluate the effects of signal strength, age, sex, optic disc size, and axial length on the normal optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular measurements with spectral domain optical coherence tomography (SD-OCT).

Methods.: In an observational, cross-sectional study, 119 eyes of 60 normal subjects of Indian origin underwent ONH, RNFL, and macular imaging with SD-OCT during the same visit. Linear mixed-modeling methods were used to evaluate the effects of signal strength, age, sex, optic disc area, and axial length on ONH, RNFL, and macular measurements.

Results.: ONH rim measurements increased and cup measurements decreased with increasing signal strengths. For a 10-unit increase in signal strength, total rim area increased by a mean of 0.1 mm2. ONH measurements also increased with increasing optic disc size. Rim measurements decreased and cup measurements increased with increasing axial length. None of the predictors influenced RNFL measurements. Macular inner retinal thickness decreased by a mean of 1.7 μm and macular full retinal thickness decreased by an average of 3.4 μm for every decade's increase in age. Sex did not influence any of the measurements.

Conclusions.: Signal strength, optic disc size, and axial length had a significant effect on ONH measurements, whereas age had a significant effect on macular measurements. None of the predictors evaluated influenced the RNFL measurements. These predictors should be considered when evaluating change in the structural measurements in glaucoma over time.

Spectral domain-optical coherence tomography (SD-OCT), a new tool for glaucoma imaging, enables scanning the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macula with higher resolution and a faster scan rate than previous versions of this technology (Stratus OCT; Carl Zeiss Meditec, Inc., Dublin, CA). 12 The greater scanning speed of SD-OCT enables acquisition of a large number of scans in a single imaging session, reducing the need for data interpolation., One such SD-OCT device, RTVue (Optovue Inc, Fremont, CA), has a scan rate of 26,000 A-scans per second, with an axial resolution of 5 μm compared with Stratus OCT, which has a scan rate of 400 scans per second and an axial resolution of 8 to 10 μm. 
Although there are several reports on the factors affecting the ONH, RNFL, and macular measurements of Stratus OCT, 3 13 not much has been reported on the factors influencing the measurements of SD-OCT devices. In a recent study, Bendschneider et al. 14 reported that the RNFL measurements of SD-OCT in normal subjects correlated significantly with the age of the subject and the axial length of the eye. In another study, Grover et al. 15 reported that the macular thickness of normal subjects with SD-OCT had no correlation with the age and sex of the subject. Similar reports on the factors influencing the ONH measurement of SD-OCT devices are not available. 
The purpose of the present study was to evaluate the effects of signal strength, age, sex, optic disc area, and axial length on the normal ONH, RNFL, and macular measurements with SD-OCT (RTVue; Optovue) in subjects of Indian origin. 
Methods
This study was an observational, cross-sectional analysis of 119 eyes of 60 normal subjects. Informed consent was obtained from all the subjects and the Ethics Committee of L.V. Prasad Eye Institute approved all methodology. All methods adhered to the tenets of the Declaration of Helsinki for research involving human subjects. 
Inclusion criteria were 18 years of age or older, best corrected visual acuity of 20/30 or better, spherical refraction within ±4.0 D, and cylinder correction within ±2.0 D. Eyes with media opacities precluding clinical examination or SD-OCT imaging were excluded. Subjects were also excluded if they had undergone previous intraocular surgery. Both eyes were included for analysis if they were eligible. 
All participants underwent a comprehensive ophthalmic examination including review of medical history, visual acuity testing, slit lamp biomicroscopy, intraocular pressure (IOP) measurement by Goldmann applanation tonometry, gonioscopy, dilated funduscopic examination, and standard automated perimetry (SAP; 24-2 Swedish Interactive Threshold Algorithm, SITA; Carl Zeiss Meditec Inc.). All the participants were staff or employees of the institute or were attending the institute for a routine eye examination. All eyes had an IOP of 21 mm Hg or less with no history of increased IOP and had normal ocular examination and SAP results. A normal SAP result was defined as a pattern standard deviation (PSD) within the 95% confidence limits and a glaucoma hemifield test (GHT) result within normal limits with less than 20% fixation losses or false-positive or false-negative responses. 
Instrumentation
SD-OCT examination was performed with the RTVue (software version 4.0.7.5). The principles and protocol used have been published. 16 The scans used for imaging were ONH (optic nerve head) and GCC (ganglion cell complex). All subjects had both the scans performed on the same day. Only well-centered images with a signal strength index (SSI) of ≥30 were used for analysis. Eyes in which the segmentation algorithm failed were excluded. 
ONH Measurements
The ONH scan was used to obtain ONH measurements. It consists of 12 radial scans 3.4 mm in length (452 A scans each) and 6 concentric ring scans ranging from 2.5 to 4.0 mm in diameter (587–775 A scans each) all centered on the optic disc. Retinal pigment epithelium (RPE) tips were automatically detected by the software and were manually refined by the operator. The software then delineated the optic disc margin by joining the RPE tips. The optic cup was automatically defined by the software by fitting a plane 150 μm parallel to and above a plane that fit the coordinates of the RPE tips by the least-squares error method. Rim tissue above the cup line and within the perpendicular lines drawn from the RPE tips to the surface of the retina was included in calculating the rim area and volume. ONH parameters studied were rim area, cup area, temporal rim area (316–45°), superior rim area (46–135°), nasal rim area (136–225°), inferior rim area (226–315°), rim volume, and cup volume. 
Peripapillary RNFL Measurements
The ONH scan also generates a polar RNFL thickness map, which is the RNFL thickness measured along a circle 3.45 mm in diameter centered on the optic disc. The RNFL thickness parameters are measured by assessing a total of 2325 data points between the anterior and posterior RNFL borders, which are demarcated automatically by the software. It gives the average RNFL thickness in the temporal (316–45°), superior (46–135°), nasal (136–225°), inferior (226–315°) quadrant as well as the overall average along the entire measurement circle. 
Macular Measurements
The GCC scan is designed to automatically measure the inner retinal thickness, which includes the nerve fiber layer, ganglion cell layer, and inner plexiform layer, collectively called the GCC. The scan consists of one horizontal line scan 7 mm in length (467 A-scans) followed by 15 vertical line scans 7 mm in length (each 400 A-scans), at 0.5-mm intervals centered 1 mm temporal to the fovea. The parameters generated by the GCC analysis and included in the analyses in this study were the average inner retinal, superior inner retinal (0–180°), and inferior inner retinal thicknesses (181–360°) and the average inner superior minus inferior retinal thickness. 
In addition to the inner retinal thickness parameters, the GCC scan also measures the full retinal thickness at the macula. The macular full retinal thickness parameters in the analyses were the average full retina thickness, the average superior and inferior quadrant full retinal thickness, and the average superior minus inferior full macular thickness. 
Statistical Analysis
Descriptive statistics included mean ± SD for normally distributed variables and median, first quartile, and third quartile values for non-normally distributed variables. Linear mixed models were fit to assess the effects of signal strength, age, sex, optic disc area, and axial length on the ONH, RNFL and macular parameters measured by SD-OCT. The linear mixed model is a parametric linear model that quantifies the relationship between a continuous dependent variable and one or more predictor variables and is specifically used with clustered, longitudinal, or repeated-measures data. 17 It can include fixed and random-effect parameters, accounting for the correlation among random-effect parameters. Whereas the fixed-effect parameters describe the relationship between the predictors and the dependent variable for the entire population, random-effect parameters describe the relationship specifically for the clusters within the population. ONH, RNFL, and macular parameters were the dependent variables and signal strength, age, sex, optic disc area, and axial length were the predictors. Signal strength, age, sex, optic disc area, and axial length were treated as fixed-effect parameters and the subject as a random-effect parameter in the mixed models. Significant interactions between the predictor variables were investigated. Signal strength and age had a significant relationship in both ONH and GCC scans (Figs. 1, 2). Younger subjects had higher signal strengths and older subjects lower signal strengths (β = −0.46 in ONH scans and β = −0.38 in GCC scans, respectively, both P < 0.001). So an interaction term between age and signal strength was introduced into the model to evaluate whether the effect of signal strength was similar or different across the entire age range. There were no other significant interactions between the predictor variables. All variables were centered on their respective means before they were introduced into the model. Statistical analyses were performed with commercial software (Stata ver. 10.0; StataCorp, College Station, TX). The α level (type I error) was set at 0.05. 
Figure 1.
 
Relationship between age and signal strength in ONH scans.
Figure 1.
 
Relationship between age and signal strength in ONH scans.
Figure 2.
 
Relationship between age and signal strength in GCC scans.
Figure 2.
 
Relationship between age and signal strength in GCC scans.
Results
Demographic and characteristic features of the study cohort are presented in Table 1. The distributions of the predictor variables in the cohort are shown in Figure 3. Average values of the ONH, RNFL, and macular parameters measured with SD-OCT are shown in Tables 2, 3, and 4
Table 1.
 
Demographic and Characteristic Features
Table 1.
 
Demographic and Characteristic Features
Mean ± SD Range
Signal strength, ONH scan 59 ± 10 32 to 86
Signal strength, GCC scan 66 ± 8 39 to 82
Age, y 47 ± 13 22 to 74
Male:female 32:28
Disc area, mm2 2.39 ± 0.39 1.55 to 3.44
Spherical equivalent refraction, D 0.23 ± 1.12 −3.25 to 4
Axial length, mm 22.71 ± 0.74 21.03 to 24.77
Figure 3.
 
Distribution of predictor variables in the cohort.
Figure 3.
 
Distribution of predictor variables in the cohort.
Table 2.
 
ONH Measurements
Table 2.
 
ONH Measurements
Parameter Mean 95% CI
Cup area 0.71 0.62–0.79
Rim area 1.68 1.60–1.76
Temporal rim area 0.25 0.22–0.28
Superior rim area 0.48 0.46–0.51
Nasal rim area 0.47 0.45–0.49
Inferior rim area 0.48 0.45–0.50
Rim volume 0.25 0.22–0.28
Cup volume 0.17 0.14–0.21
Table 3.
 
RNFL Measurements
Table 3.
 
RNFL Measurements
RNFL Quadrant Mean 95% CI
Temporal 75.8 74.3–77.3
Superior 134.4 131.4–137.4
Nasal 83.6 81.1–86.1
Inferior 139.7 136.7–142.6
Average thickness 108.4 106.6–110.3
Table 4.
 
Macular Measurements
Table 4.
 
Macular Measurements
Macular Parameter Mean 95% CI
Macular inner retinal average, μm 96.5 95.3 to 97.8
Inner retinal superior average, μm 95.7 94.5 to 96.9
Inner retinal inferior average, μm 97.4 96.1 to 98.7
Inner SI average, μm −1.7 −2.4 to −1.0
Full macular average, μm 265.1 262.4 to 267.9
Full macular superior average, μm 265.3 262.6 to 268.0
Full macular inferior average, μm 264.9 262.0 to 267.9
Full macular SI average, μm 0.4 −0.7 to 1.4
The effect of the predictor variables on the ONH measurements are shown in Table 5. Signal strength, optic disc area, and axial length had a significant effect on all or most of the ONH parameters. Rim measurements increased and cup measurements decreased with increasing signal strengths. For example, for every 10-unit increase in the signal strength, cup area decreased by 0.1 mm2, whereas total rim area increased by 0.1 mm2. Optic disc area had a significant positive influence on most of the ONH parameters. ONH parameter measurements increased with an increase in optic disc size. Axial length had a significant positive influence on the cup measurements and a significant negative influence on the rim measurements. For each 1-mm increase in axial length, cup area increased by 0.15 mm2 and rim area decreased by 0.15 mm2. Age and sex had no influence on the ONH measurements. The interaction term between signal strength and age significantly influenced all the ONH measurements, meaning that the effect of signal strength was not similar across the entire age range. Figure 4 shows the effect of signal strength on total rim area measurement with SD-OCT for mean values of disc area and axial length. Figure 5 shows the effect of disc area on total rim area measurement for mean values of signal strength and axial length. Figure 6 shows the effect of axial length on total rim area measurement for mean values of signal strength and disc area. 
Table 5.
 
Effect of Predictor Variables on the ONH Measurements
Table 5.
 
Effect of Predictor Variables on the ONH Measurements
Parameter Signal Strength Age Sex Disc Area Axial Length Signal Strength × Age
β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P
Cup area −0.01 (0.003) 0.001 −0.002 (0.004) 0.66 −0.004 (0.11) 0.97 0.46 (0.07) <0.001 0.15 (0.07) 0.03 0.001 (0.001) 0.003
Rim area 0.01 (0.001) 0.001 0.002 (0.004) 0.66 0.003 (0.11) 0.98 0.54 (0.07) <0.001 −0.15 (0.07) 0.03 −0.001 (0.001) 0.002
Temporal rim area 0.003 (0.001) 0.02 −0.001 (0.001) 0.78 −0.01 (0.04) 0.83 0.06 (0.03) 0.08 −0.03 (0.02) 0.22 −0.001 (0.000) 0.004
Superior rim area 0.002 (0.001) 0.04 0.001 (0.001) 0.38 −0.01 (0.03) 0.67 0.14 (0.03) <0.001 −0.05 (0.02) 0.003 −0.001 (0.000) <0.001
Nasal rim area 0.002 (0.001) 0.07 0.001 (0.001) 0.29 0.02 (0.03) 0.49 0.13 (0.02) <0.001 −0.04 (0.02) 0.04 −0.001 (0.000) 0.04
Inferior rim area 0.003 (0.001) 0.004 0.001 (0.001) 0.68 −0.001 (0.03) 0.97 0.12 (0.02) <0.001 −0.05 (0.02) 0.01 −0.000 (0.000) 0.02
Rim volume 0.003 (0.001) 0.002 −0.001 (0.001) 0.69 0.02 (0.04) 0.66 0.02 (0.03) 0.53 −0.06 (0.02) 0.01 −0.000 (0.000) 0.01
Cup volume −0.003 (0.001) 0.01 −0.002 (0.002) 0.17 −0.005 (0.04) 0.91 0.16 (0.03) <0.001 0.06 (0.03) 0.02 0.000 (0.000) 0.004
Figure 4.
 
Effect of signal strength on total rim area measurement at mean disc areas and axial lengths.
Figure 4.
 
Effect of signal strength on total rim area measurement at mean disc areas and axial lengths.
Figure 5.
 
Effect of optic disc size on total rim area measurement at mean signal strengths and axial lengths.
Figure 5.
 
Effect of optic disc size on total rim area measurement at mean signal strengths and axial lengths.
Figure 6.
 
Effect of axial length on total rim area measurement at mean signal strengths and optic disc areas.
Figure 6.
 
Effect of axial length on total rim area measurement at mean signal strengths and optic disc areas.
The effect of the predictor variables in the RNFL measurements are shown in Table 6. None of the predictor variables had an influence on the RNFL measurements of SD-OCT in normal subjects. 
Table 6.
 
Effect of Predictor Variables on RNFL Measurements
Table 6.
 
Effect of Predictor Variables on RNFL Measurements
RNFL Sector Signal Strength Age Sex Disc Area Axial Length Signal Strength × Age
β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P
Temporal −0.12 (0.10) 0.22 −0.11 (0.09) 0.20 −3.11 (2.17) 0.15 −0.23 (2.21) 0.92 2.15 (1.40) 0.13 0.001 (0.006) 0.93
Superior −0.01 (0.18) 0.96 −0.12 (0.17) 0.47 −4.14 (4.34) 0.34 7.46 (4.14) 0.07 0.47 (2.78) 0.87 0.001 (0.01) 0.93
Nasal 0.14 (0.15) 0.38 −0.14 (0.14) 0.32 −1.63 (3.52) 0.64 −1.25 (3.55) 0.73 −3.27 (2.27) 0.15 0.008 (0.009) 0.38
Inferior 0.24 (0.17) 0.16 0.09 (0.17) 0.61 −0.41 (4.38) 0.93 2.16 (4.01) 0.59 −4.78 (2.79) 0.09 0.02 (0.01) 0.12
Average 0.09 (0.09) 0.28 −0.06 (0.11) 0.59 −2.11 (2.79) 0.45 −0.10 (2.14) 0.96 −2.06 (1.72) 0.23 0.008 (0.006) 0.20
The effects of the predictor variables on macular measurements are shown in Table 7. Age had a significant but weak (R 2 < 10%) negative influence on both the macular inner retinal and full retinal thickness measurements. Macular inner retinal average thickness, for example, decreased by an average of 1.7 μm for every decade's increase in age. Macular full retinal average thickness decreased by an average of 3.4 μm for every decade's increase in age. Macular superior minus inferior average thickness was not influenced by age, indicating that the decline in superior and inferior thickness measurements was similar, so that the difference remained constant. Signal strength, sex, disc size, and axial length did not have an influence on the macular measurements in normal subjects. Figure 7 shows the effect of age on the macular inner retinal thickness average measurement. Figure 8 shows the effect of age on the macular full retinal thickness average measurement. 
Table 7.
 
Effect of Predictor Variables on Macular Measurements
Table 7.
 
Effect of Predictor Variables on Macular Measurements
Parameter Signal Strength Age Sex Disc Area Axial Length Signal Strength × Age
β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P
Inner Retina
Average −0.09 (0.08) 0.27 −0.17 (0.07) 0.02 0.09 (1.81) 0.96 −1.31 (1.53) 0.39 0.63 (1.15) 0.58 0.002 (0.005) 0.64
Superior average −0.11 (0.09) 0.21 −0.16 (0.07) 0.03 −0.02 (1.81) 0.99 −0.92 (1.61) 0.57 1.01 (1.16) 0.38 0.001 (0.005) 0.92
Inferior average −0.07 (0.09) 0.43 −0.19 (0.08) 0.02 0.19 (1.92) 0.92 −1.84 (1.69) 0.27 0.25 (1.22) 0.84 0.004 (0.005) 0.43
SI average −0.03 (0.06) 0.62 0.03 (0.04) 0.39 −0.002 (0.87) 0.99 0.90 (0.96) 0.35 0.55 (0.56) 0.33 −0.002 (0.003) 0.53
Full Retina
Average 0.12 (0.12) 0.33 −0.34 (0.16) 0.03 2.29 (4.05) 0.57 −4.32 (2.45) 0.08 0.79 (2.40) 0.74 0.005 (0.008) 0.58
Superior average 0.09 (0.12) 0.42 −0.34 (0.15) 0.03 1.30 (4.00) 0.75 −2.41 (2.34) 0.30 1.25 (2.35) 0.60 −0.000 (0.008) 0.96
Inferior average 0.14 (0.15) 0.39 −0.35 (0.16) 0.03 3.37 (4.25) 0.43 −4.22 (2.96) 0.06 0.19 (2.61) 0.94 0.01 (0.01) 0.31
SI average 0.04 (0.09) 0.62 0.05 (0.06) 0.43 −1.85 (1.37) 0.18 0.99 (1.46) 0.50 0.72 (0.88) 0.41 −0.005 (0.005) 0.29
Figure 7.
 
Effect of age on macular inner retinal average thickness measurement.
Figure 7.
 
Effect of age on macular inner retinal average thickness measurement.
Figure 8.
 
Effect of age on macular full retinal average thickness measurement.
Figure 8.
 
Effect of age on macular full retinal average thickness measurement.
We also evaluated the effect of refractive error (spherical equivalent) on the SD-OCT measurements in a separate model after substituting it for axial length as both axial length and refractive error were significantly related to each other (β = −0.55, P < 0.001). Results from the model showed that refractive error had a positive influence on the rim measurements and a negative influence on the cup measurements. For a 1-D increase in the spherical equivalent refraction, rim area increased by 0.02 mm2 and cup area decreased by 0.02 mm2. Refractive error did not affect the RNFL and macular measurements (P > 0.05 for all associations). 
Discussion
Evaluating the predictors of normal ONH, RNFL, and macular parameters measured with SD-OCT (RTVue; Optovue), we found that signal strength, optic disc size, and axial length had a significant effect on ONH measurements, and age had a significant effect on macular measurements. None of the predictors evaluated influenced the RNFL measurements. To our knowledge, this is the first study to evaluate the factors influencing the ONH, RNFL, and macular measurements with SD-OCT in normal subjects. 
Signal strength had a significant influence on all the ONH measurements. ONH rim measurements increased and ONH cup measurements decreased with the increase in signal strength. Signal strength did not influence the RNFL and macular measurements. Although there are no reports on the effect of signal strength on SD-OCT measurements, there are a few studies on the effect of signal strength on Stratus OCT. Samarawickrama et al., 18 in a large cohort of children, found similar results of signal strength on the ONH measurements with Stratus OCT. The effect of signal strength in the study by Samarawickrama et al. was insignificant on RNFL measurements and, although statistically significant, was minimal clinically on macular measurements. Cheung et al. 19 and Wu et al. 20 reported a significant effect of signal strength on the RNFL measurements with Stratus OCT. It is also important to note that the signal strengths between instruments may not be comparable, as each use a proprietary scale. For example, the signal strength index of RTVue ranges from 0 to 100, whereas that of Stratus OCT ranges from 0 to 10. It is possible that the signal strengths of different devices may affect the measurements differently. In our study, total neuroretinal rim area decreased by 0.1 mm2 for every 10-unit decrease in the signal strength, which means that between the change in signal strengths from 80 to 30 (both within the manufacturers' acceptable range), the change in rim area could be as much as 0.5 mm2. Images with lower signal strengths could falsely be labeled glaucomatous. Future studies with imaging devices should consider and evaluate the effect of signal strength on the measurements. 
Age had a significant but weak effect on macular measurements in our study. Our results are similar to the reports on Stratus OCT by Sung et al. 3 and Eriksson and Alm 11 Full macular thickness decreased by 3.4 μm per decade in our study. Overall macular thickness decreased by 4.2 μm per decade in the study by Sung et al. 3 In two recent studies of SD-OCT, Huang et al. 12 and Grover et al. 15 failed to detect a significant effect of age on macular measurements. This result may have been caused by the small sample size (n = 32) in the study by Huang et al. and because the subjects in Grover et al. 15 were categorized into groups based on age, thereby losing power to detect significant associations. Age did not influence ONH or RNFL measurements with RTVue in our study. Bendschneider et al. 14 using a different SD-OCT device, reported significant negative correlation between age and RNFL thickness. Sung et al., 3 in a similar study with Stratus OCT, reported that with increasing age, most of the RNFL parameters decreased and ONH rim area decreased. Similar reports of RNFL thickness decreasing with age have been reported by different groups; the decrease in average RNFL thickness in several studies has ranged from 0.9 μm per decade to 3.2 μm per decade. 4 8,13 Although studies with OCTs have reported consistent negative correlation between age and RNFL thickness measurements, histologic studies evaluating the relationship between ganglion cell axon number and age have reported contradictory results. Although Balazsi et al. 21 reported a negative correlation between age and axonal number, in later work Mikelberg et al. 22 and Repka and Quigley 23 found no correlation. Most of the studies with Stratus OCT have used a signal strength of 7 or better for inclusion but have not actually looked at the association between signal strength and OCT measurements or between signal strength and age. In our study, we found a significant negative relationship between age and most of the SD-OCT measurements in models without signal strength. Inclusion of signal strength in the model revealed an insignificant association between age and RNFL measurements. The possibility that signal strength is a confounder in the association between age and RNFL measurements should be considered. Our results highlight the importance of including all appropriate predictors and looking for significant interactions between predictors while evaluating the effect of each on OCT measurements. 
Optic disc size significantly influenced the measurement of ONH parameters, but did not influence the RNFL and macular measurements in our study. Although there are no reports on the effect of optic disc size on ONH and macular measurements, our results are in contrast to the earlier reports on the effect of optic disc size on RNFL measurements. Earlier studies have found a positive correlation between optic disc area and RNFL thickness. 4,8,14,24 A histologic study, too, has found that RNFL thickness decreases with increasing distance from the disc margin. 25 These results mean that when measuring RNFL thickness with a fixed-diameter circle centered on the optic disc, RNFL thickness measurements in eyes with small optic discs are lesser because of the distance between the circle and the optic disc margin, compared with eyes with large optic discs. One of the reasons for not finding a correlation between disc size and RNFL thickness in our study may be the underrepresentation of eyes with small discs (only 23 eyes with disc area <2 mm2 and none with disc area <1.5 mm2). 
Axial length and refractive error significantly influenced the measurement of ONH parameters in our study. Rim measurements decreased and cup measurements increased with increase in axial length. The effect of refractive error on these measurements was in the opposite direction. There is a possible bias in these findings, however. It is important to note that the ONH measurements by OCT were not corrected for the axial length, and it has been reported that the corrected ONH measurements by the OCT are in fact significantly larger than the uncorrected measurements. 26 Unfortunately, there is no commercially available software that compensates for this disparity. Alternatively, the change in rim and cup measurements associated with axial length found in our study may indicate the cup shape/configuration change with change in the actual disc size rather than a true influence. Axial length and refractive error did not influence the RNFL and macular measurements in our study. Most studies evaluating the relationship between axial length/refractive error and RNFL thickness have found a significant correlation. 4,8,13,14,27 As there is a possibility that refractions < −0.5 D and >0.5 D had opposite effects on the RNFL measurements and resulted in a statistically insignificant effect of axial length/refractive error on the RNFL measurements, we did a subgroup analysis using only the eyes with ≤ −0.5-D refractive error (18 eyes of 11 subjects). Even then, axial length and refractive error had no influence on the RNFL measurements (P > 0.20 for all analyses). We may have failed to detect a significant effect of axial length/refractive error on RNFL thickness measurement due to a narrow range of these variables in our study. 
We also found no association between the SD-OCT measurements and the sex of the subject. Similar results have been reported by different groups who evaluated this relationship in measurements obtained by Stratus OCT. 4,7,1415,28  
Comparing the ONH, RNFL, and macular measurements with RTVue in normal subjects of Indian origin with the measurements reported by other groups who used RTVue in Caucasians, we found differences for most of the ONH, RNFL, and macular measurements. ONH measurements in our study were greater than those reported in Caucasians, 29 which is probably explained by the smaller optic discs in Caucasian subjects compared with Indians. 30 Most of the RNFL measurements were also thicker in Indian subjects than those reported in Caucasian subjects. 29,31 Macular thickness measurements in the Indian population were also higher than those reported by Tan et al. 32 in a group of normal, predominantly Caucasian subjects. RNFL measurements with RTVue in our study were similar to the RNFL measurements reported with Stratus OCT in an Indian population. 7,28 Budenz et al. 4 also have reported thicker RNFL measurements with Stratus OCT in Asians than in Caucasians. These results emphasize the importance of considering the racial differences in ONH, RNFL, and macular measurements in addition to the predictors evaluated herein, during the development of a normative database for glaucoma detection. 
In conclusion, in evaluating the effect of predictors on the ONH, RNFL, and macular measurements of SD-OCT, we found that signal strength, optic disc size, and axial length had a significant effect on ONH measurements, and age had a significant effect on macular measurements. None of the predictors evaluated influenced the RNFL measurements. These predictors should be considered while evaluating change in the structural measurements in glaucoma over time. 
Footnotes
 Disclosure: H.L. Rao, None; A.U. Kumar, None; J.G. Babu, None; A. Kumar, None; S. Senthil, None; C.S. Garudadri, Optovue (F), Allergan (C), Merck (C), Alcon (C)
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Figure 1.
 
Relationship between age and signal strength in ONH scans.
Figure 1.
 
Relationship between age and signal strength in ONH scans.
Figure 2.
 
Relationship between age and signal strength in GCC scans.
Figure 2.
 
Relationship between age and signal strength in GCC scans.
Figure 3.
 
Distribution of predictor variables in the cohort.
Figure 3.
 
Distribution of predictor variables in the cohort.
Figure 4.
 
Effect of signal strength on total rim area measurement at mean disc areas and axial lengths.
Figure 4.
 
Effect of signal strength on total rim area measurement at mean disc areas and axial lengths.
Figure 5.
 
Effect of optic disc size on total rim area measurement at mean signal strengths and axial lengths.
Figure 5.
 
Effect of optic disc size on total rim area measurement at mean signal strengths and axial lengths.
Figure 6.
 
Effect of axial length on total rim area measurement at mean signal strengths and optic disc areas.
Figure 6.
 
Effect of axial length on total rim area measurement at mean signal strengths and optic disc areas.
Figure 7.
 
Effect of age on macular inner retinal average thickness measurement.
Figure 7.
 
Effect of age on macular inner retinal average thickness measurement.
Figure 8.
 
Effect of age on macular full retinal average thickness measurement.
Figure 8.
 
Effect of age on macular full retinal average thickness measurement.
Table 1.
 
Demographic and Characteristic Features
Table 1.
 
Demographic and Characteristic Features
Mean ± SD Range
Signal strength, ONH scan 59 ± 10 32 to 86
Signal strength, GCC scan 66 ± 8 39 to 82
Age, y 47 ± 13 22 to 74
Male:female 32:28
Disc area, mm2 2.39 ± 0.39 1.55 to 3.44
Spherical equivalent refraction, D 0.23 ± 1.12 −3.25 to 4
Axial length, mm 22.71 ± 0.74 21.03 to 24.77
Table 2.
 
ONH Measurements
Table 2.
 
ONH Measurements
Parameter Mean 95% CI
Cup area 0.71 0.62–0.79
Rim area 1.68 1.60–1.76
Temporal rim area 0.25 0.22–0.28
Superior rim area 0.48 0.46–0.51
Nasal rim area 0.47 0.45–0.49
Inferior rim area 0.48 0.45–0.50
Rim volume 0.25 0.22–0.28
Cup volume 0.17 0.14–0.21
Table 3.
 
RNFL Measurements
Table 3.
 
RNFL Measurements
RNFL Quadrant Mean 95% CI
Temporal 75.8 74.3–77.3
Superior 134.4 131.4–137.4
Nasal 83.6 81.1–86.1
Inferior 139.7 136.7–142.6
Average thickness 108.4 106.6–110.3
Table 4.
 
Macular Measurements
Table 4.
 
Macular Measurements
Macular Parameter Mean 95% CI
Macular inner retinal average, μm 96.5 95.3 to 97.8
Inner retinal superior average, μm 95.7 94.5 to 96.9
Inner retinal inferior average, μm 97.4 96.1 to 98.7
Inner SI average, μm −1.7 −2.4 to −1.0
Full macular average, μm 265.1 262.4 to 267.9
Full macular superior average, μm 265.3 262.6 to 268.0
Full macular inferior average, μm 264.9 262.0 to 267.9
Full macular SI average, μm 0.4 −0.7 to 1.4
Table 5.
 
Effect of Predictor Variables on the ONH Measurements
Table 5.
 
Effect of Predictor Variables on the ONH Measurements
Parameter Signal Strength Age Sex Disc Area Axial Length Signal Strength × Age
β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P
Cup area −0.01 (0.003) 0.001 −0.002 (0.004) 0.66 −0.004 (0.11) 0.97 0.46 (0.07) <0.001 0.15 (0.07) 0.03 0.001 (0.001) 0.003
Rim area 0.01 (0.001) 0.001 0.002 (0.004) 0.66 0.003 (0.11) 0.98 0.54 (0.07) <0.001 −0.15 (0.07) 0.03 −0.001 (0.001) 0.002
Temporal rim area 0.003 (0.001) 0.02 −0.001 (0.001) 0.78 −0.01 (0.04) 0.83 0.06 (0.03) 0.08 −0.03 (0.02) 0.22 −0.001 (0.000) 0.004
Superior rim area 0.002 (0.001) 0.04 0.001 (0.001) 0.38 −0.01 (0.03) 0.67 0.14 (0.03) <0.001 −0.05 (0.02) 0.003 −0.001 (0.000) <0.001
Nasal rim area 0.002 (0.001) 0.07 0.001 (0.001) 0.29 0.02 (0.03) 0.49 0.13 (0.02) <0.001 −0.04 (0.02) 0.04 −0.001 (0.000) 0.04
Inferior rim area 0.003 (0.001) 0.004 0.001 (0.001) 0.68 −0.001 (0.03) 0.97 0.12 (0.02) <0.001 −0.05 (0.02) 0.01 −0.000 (0.000) 0.02
Rim volume 0.003 (0.001) 0.002 −0.001 (0.001) 0.69 0.02 (0.04) 0.66 0.02 (0.03) 0.53 −0.06 (0.02) 0.01 −0.000 (0.000) 0.01
Cup volume −0.003 (0.001) 0.01 −0.002 (0.002) 0.17 −0.005 (0.04) 0.91 0.16 (0.03) <0.001 0.06 (0.03) 0.02 0.000 (0.000) 0.004
Table 6.
 
Effect of Predictor Variables on RNFL Measurements
Table 6.
 
Effect of Predictor Variables on RNFL Measurements
RNFL Sector Signal Strength Age Sex Disc Area Axial Length Signal Strength × Age
β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P
Temporal −0.12 (0.10) 0.22 −0.11 (0.09) 0.20 −3.11 (2.17) 0.15 −0.23 (2.21) 0.92 2.15 (1.40) 0.13 0.001 (0.006) 0.93
Superior −0.01 (0.18) 0.96 −0.12 (0.17) 0.47 −4.14 (4.34) 0.34 7.46 (4.14) 0.07 0.47 (2.78) 0.87 0.001 (0.01) 0.93
Nasal 0.14 (0.15) 0.38 −0.14 (0.14) 0.32 −1.63 (3.52) 0.64 −1.25 (3.55) 0.73 −3.27 (2.27) 0.15 0.008 (0.009) 0.38
Inferior 0.24 (0.17) 0.16 0.09 (0.17) 0.61 −0.41 (4.38) 0.93 2.16 (4.01) 0.59 −4.78 (2.79) 0.09 0.02 (0.01) 0.12
Average 0.09 (0.09) 0.28 −0.06 (0.11) 0.59 −2.11 (2.79) 0.45 −0.10 (2.14) 0.96 −2.06 (1.72) 0.23 0.008 (0.006) 0.20
Table 7.
 
Effect of Predictor Variables on Macular Measurements
Table 7.
 
Effect of Predictor Variables on Macular Measurements
Parameter Signal Strength Age Sex Disc Area Axial Length Signal Strength × Age
β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P β (SE) P
Inner Retina
Average −0.09 (0.08) 0.27 −0.17 (0.07) 0.02 0.09 (1.81) 0.96 −1.31 (1.53) 0.39 0.63 (1.15) 0.58 0.002 (0.005) 0.64
Superior average −0.11 (0.09) 0.21 −0.16 (0.07) 0.03 −0.02 (1.81) 0.99 −0.92 (1.61) 0.57 1.01 (1.16) 0.38 0.001 (0.005) 0.92
Inferior average −0.07 (0.09) 0.43 −0.19 (0.08) 0.02 0.19 (1.92) 0.92 −1.84 (1.69) 0.27 0.25 (1.22) 0.84 0.004 (0.005) 0.43
SI average −0.03 (0.06) 0.62 0.03 (0.04) 0.39 −0.002 (0.87) 0.99 0.90 (0.96) 0.35 0.55 (0.56) 0.33 −0.002 (0.003) 0.53
Full Retina
Average 0.12 (0.12) 0.33 −0.34 (0.16) 0.03 2.29 (4.05) 0.57 −4.32 (2.45) 0.08 0.79 (2.40) 0.74 0.005 (0.008) 0.58
Superior average 0.09 (0.12) 0.42 −0.34 (0.15) 0.03 1.30 (4.00) 0.75 −2.41 (2.34) 0.30 1.25 (2.35) 0.60 −0.000 (0.008) 0.96
Inferior average 0.14 (0.15) 0.39 −0.35 (0.16) 0.03 3.37 (4.25) 0.43 −4.22 (2.96) 0.06 0.19 (2.61) 0.94 0.01 (0.01) 0.31
SI average 0.04 (0.09) 0.62 0.05 (0.06) 0.43 −1.85 (1.37) 0.18 0.99 (1.46) 0.50 0.72 (0.88) 0.41 −0.005 (0.005) 0.29
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