The relationship between cup-to-disc ratio and estimated number of retinal ganglion cells

Abstract

Purpose: To investigate the relationship between cup-to-disc ratio (CDR) and estimates of retinal ganglion cell (RGC) number.

Methods: This cross-sectional study included 156 healthy eyes, 53 glaucoma suspects, and 127 eyes with glaucoma. All eyes had standard automated perimetry (SAP), Cirrus SD-OCT, and stereoscopic optic disc photography within 6 months. CDR was determined from stereoscopic photographs by two or more masked graders. The number of RGCs in each eye was estimated using a published model that combines estimates of RGC number from SAP sensitivity thresholds and SD-OCT retinal nerve fiber layer measurements.

Results: The mean estimated RGC count was 1,063,809 in healthy eyes; 828,522 in eyes with suspected glaucoma; and 774,200 in early, 468,568 in moderate, and 218,471 in advanced glaucoma. Healthy eyes had a mean vertical CDR of 0.45 ± 0.15 vs. 0.80 ± 0.16 in glaucomatous eyes. There was good correlation between stereophotographic vertical CDR and SD-OCT vertical CDR (R(2) = 0.825; P < 0.001). The relationship between estimated RGCs and vertical CDR was best represented using a third degree polynomial regression model, including age and optic disc area, which accounted for 83.3% of the variation in estimated RGC counts. The nonlinear relationship between RGC estimates and CDRs indicated that eyes with a large CDR would require loss of large RGC numbers for a small increase in CDR.

Conclusions: The relationship between estimated RGC counts and CDR suggests that assessment of change in CDR is an insensitive method for evaluation of progressive neural losses in glaucoma. Even relatively small changes in CDR may be associated with large losses of RGCs, especially in eyes with large CDRs. (ClinicalTrials.gov numbers, NCT00221923, NCT00221897.).

Keywords: ganglion cell; glaucoma; optic disc; optical coherence tomography; perimetry.

Figure 1

Scatterplots and ordinary least squares (OLS) regression lines showing the relationship between (A) stereophotograph vertical CDR and Cirrus OCT vertical CDR and (B) stereophotograph average CDR and Cirrus OCT average CDR.

Figure 2

Scatterplot showing the relationship between estimated RGC number and stereophotograph vertical CDR. The locally weighted scatterplot smoothing (LOWESS) curve is shown.

Figure 3

Relationship between estimated RGC number and stereophotograph vertical CDR as fitted by the polynomial regression model. Bars include 95% confidence interval for mean values of estimated RGC number. Results are given for age and optic disc area corresponding to average values in the sample (age = 57.7 years and disc area = 1.87 mm²).

Figure 4

Expected number of RGCs for given values of CDR based on the results of the polynomial regression model for arbitrary values of age (60 and 80 years) and for small (1.5 mm²), medium (2.0 mm²), and large (2.5 mm²) optic disc areas.

Figure 5

Example of a glaucomatous left eye of a 76-year-old patient included in the study. The figure shows the stereophotograph of the optic disc (A), the Cirrus OCT RNFL thickness and deviation maps (B), and the SAP gray scale and threshold values (C). The stereophotographic vertical CDR was graded as 1.0. The disc area was 1.82 mm² and the mean RNFL thickness was 61 μm. The estimated number of RGCs for this eye was 117,621.

Figure 6

Example of a healthy right eye of a 54-year-old subject included in the study. The figure shows the stereophotograph of the optic disc (A), the Cirrus OCT RNFL thickness and deviation maps (B), and the SAP gray scale and threshold values (C). The stereophotographic vertical CDR was graded as 0.35. The disc area was 1.99 mm² and the mean RNFL thickness was 87 μm. The estimated number of RGCs for this eye was 961,783.