Visual field defects and retinal ganglion cell losses in patients with glaucoma

Abstract

Objective: To determine whether the structure-function relationships for glaucoma in humans and experimental glaucoma in monkeys are similar.

Methods: The study was based on retinal ganglion cell density and visual thresholds in patients with documented glaucoma. Data were analyzed with a model that predicted ganglion cell density from standard clinical perimetry, which was then compared with histologic cell counts.

Results: The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell density associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs measured cell density had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs measured values was 2.59 decibels (dB), and the mean +/- SD of the distribution of residual errors of prediction was -0.26 +/- 3.22 dB.

Conclusions: Visual field defects based on standard clinical perimetry are proportional to neural losses caused by glaucoma.

Clinical relevance: The evidence for quantitative structure-function relationships provides a scientific basis for interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease.

Fig. 1

Test field locations from the Humphrey Field Analyzer C24-2 program (Carl-Zeiss Meditec, Dublin, Calif ) that corresponded to retinal locations of the tissue samples for histologic cell counts. The symbols represent the 28 sites that were used for the correlation of retinal ganglion cell density and visual field sensitivity in eyes of patients with glaucoma. The symbol shapes that are used to designate visual field locations for retinal tissue samples are also used in Figures 2 and 3 to represent the visual field and retinal locations of the data for comparing the predicted and measured ganglion cell density.

Fig. 2

The application of the model for structure-function to glaucoma patients and monkeys with experimental glaucoma. The upper graphs (A & C) represent the relationships between ganglion cell densities predicted from perimetry measurements of visual sensitivity as a function of the histological measurements of cell density. The different symbol shapes designate different locations in the visual field, as indicated by the sites of retina samples in Fig. 1. The model prediction of unity correlation is shown by the one-to-one line that is superimposed on the data. Goodness-of-fit statistics for the mean absolute deviation (MAD) and coefficient of determination (r²) are presented as insets and the limits of agreement (95% confidence limits) are illustrated by the dashed lines on each graph. The lower histograms (B & D) present the distribution of residual errors (DRE) of the model with respect to the one-to-one relationship, with errors of greater predicted than measured cell densities designated as negative errors and errors for greater measured than predicted cell densities designated as positive errors. The mean and SD’s of the distributions are shown by insets and the percentage of errors that are less than ± 3 dB are indicated by the darker bars.

Fig. 3

Results after applying the model for structure-function to the data for individual eyes in patients with glaucoma. Details of the data are the same as for the group data in Figure 3, and details of patients and model results are given in the Table.