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A-12
Appendix
2Age
The CIRRUS RNFL normative database was developed utilizing 282 subjects aged 19 to 84.
Disc Area and Cup Volume showed no effect of Age. The Rim Area decreases slowly with
age (slope = –0.002 mm
2
/ year, R
2
= 0.033, p = 0.002), while CDR (average and vertical)
2
increased slowly with age (slope = +0.002 per year, R
= 0.032, p = 0.002 for average
CDR, slope = +0.002 per year, R
2
= 0.041, p = 0.001 for vertical CDR). As expected, disc
area does not change with age (p > 0.05).
Optic Disc Area
The distribution of disc area for the normative database eyes is discussed in the paragraph
above. Note that the majority of disc areas were between 1.3 mm
2
and 2.5 mm
2
.
Therefore, normal limits will not be well defined for this population outside of those disc
sizes, and are not applied in CIRRUS. All optic nerve head parameters increase with disc
size, including Rim Area (slope = +0.24 mm
2
of rim per mm
2
of disc, R
2
= 0.13, p =
0.042), Cup Volume (slope = +0.25 mm
3
of cup per mm
2
of disc, R
2
= 0.39, p = 0.011),
2
2
and Cup to Disc Ratios (slope = +0.35 per mm
of disc, R
= 0.35, p = 0.001 for average
2
2
CDR, slope = +0.29 per mm
of disc, R
= 0.34, p = 0.001 for vertical CDR).
Ethnicity
The ethnicity breakdown of the CIRRUS RNFL normative database is as follows: 43%
Caucasians, 24% Asians, 18% African American, 12% Hispanic, 1% Indian, and 2% mixed
ethnicity. As expected, subjects of African descent had the largest discs on average (1.93 ±
0.33 mm
2
), while those of European descent had the smallest (1.68 ± 0.30 mm
2
, p <<
0.001). There was no statistically significant difference among different ethnicities with
respect to the Rim Area (p = 0.16). The Cup to Disc Ratio (Average and Vertical) as well as
the Cup Volume, showed differences among ethnicity groups (mean difference in ACDR is
0.10, p = 0.008, mean difference in VCDR is 0.09, p = 0.027, mean difference in Cup
3
Volume is 0.09 mm
, p = 0.003).
Calculation of Normal Limits
Analysis of the ONH parameters found that these parameters depend on both optic disc
area of the subject eye and subject age. A linear fit is used to model the age effects. The
variability of parameters such as Rim Area and Cup to Disc Ratio on Disc Area was found to
depend on the size of the disc. For this reason, quantile regression was used rather than
linear regression to set the limits on the ONH parameters with respect to Disc Area. This is
3
a method whereby the slope and offset are independently fit for each limit. See Artes et al
for a description of quantile regression. For the Average and Vertical Cup–to–Disc Ratios,
data with a Cup–to–Disc ratio less than or equal to 0.25 were excluded prior to performing
the quantile regression.
3 Artes, PH and Crabb, DP. "Estimating normative limits of Heidelberg Retina Tomograph optic disc rim area with quantile regres-
sion," Invest Ophthalmol Vis Sci. 2010 Jan;51(1):335-61
2660021169012 Rev. A 2017-12
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