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Clinical Sciences | ONLINE FIRST

A Combined Index of Structure and Function for Staging Glaucomatous Damage

Felipe A. Medeiros, MD, PhD; Renato Lisboa, MD; Robert N. Weinreb, MD; Christopher A. Girkin, MD; Jeffrey M. Liebmann, MD; Linda M. Zangwill, PhD
Arch Ophthalmol. 2012;130(9):1107-1116. doi:10.1001/archophthalmol.2012.827.
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Objectives  To present and evaluate a new combined index of structure and function (CSFI) for staging and detecting glaucomatous damage.

Methods  Observational study including 333 glaucomatous eyes (295 with perimetric glaucoma and 38 with preperimetric glaucoma) and 330 eyes of healthy subjects. All the eyes were tested with standard automated perimetry and spectral domain optical coherence tomography within 6 months. Estimates of the number of retinal ganglion cells (RGCs) were obtained from standard automated perimetry and spectral domain optical coherence tomography and a weighted averaging scheme was used to obtain a final estimate of the number of RGCs for each eye. The CSFI was calculated as the percent loss of RGCs obtained by subtracting estimated from expected RGC numbers. The performance of the CSFI for discriminating glaucoma from normal eyes and the different stages of disease was evaluated by receiver operating characteristic curves.

Results  The mean CSFI, representing the mean estimated percent loss of RGCs, was 41% and 17% in the perimetric and preperimetric groups, respectively (P < .001). They were both significantly higher than the mean CSFI in the healthy group (P < .001). The CSFI had larger receiver operating characteristic curve areas than isolated indexes of structure and function for detecting perimetric and preperimetric glaucoma and differentiating among early, moderate, and advanced stages of visual field loss.

Conclusion  An index combining structure and function performed better than isolated structural and functional measures for detection of perimetric and preperimetric glaucoma as well as for discriminating different stages of the disease.

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Figures

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Figure 1. Scatterplot illustrating the relationship between the number of retinal ganglion cells (RGCs) derived from standard automated perimetry (SAP) sensitivity data and the number of RGCs estimated from analysis of the retinal nerve fiber layer by spectral domain optical coherence tomography (SDOCT).

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Figure 2. Histograms illustrating the distribution of the number of estimated retinal ganglion cells (RGCs) according to the different diagnostic categories.

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Figure 3. Relationship between the weighted estimate of number of retinal ganglion cells (RGCs) and age. A locally weighted scatterplot smoothing (lowess) shows that a linear regression fits the data well. SAP indicates standard automated perimetry.

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Figure 4. Box plots illustrating the distribution of the values of the combined index of structure and function (CSFI) according to the different diagnostic categories. The horizontal line in the box indicates the median.

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Figure 5. Receiver operating characteristic (ROC) curves for discriminating between perimetric glaucoma and healthy eyes (A) and between preperimetric glaucoma and healthy eyes (B). ROC curves are shown for the parameters of combined index of structure and function (CSFI), average retinal nerve fiber layer (RNFL) thickness, and visual field index (VFI).

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Figure 6. Scatterplots showing the relationship between mean deviation (MD) and the combined index of structure and function (CSFI) and the average retinal nerve fiber layer (RNFL) thickness. A, Scatterplot showing the relationship between MD and the CSFI with superimposed locally weighted scatterplot smoothing (lowess). B, Scatterplot illustrating the relationship between MD and average RNFL thickness with superimposed lowess. There is much more scatter around the lowess curve for the average RNFL thickness compared with the CSFI.

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Figure 7. Eye with preperimetric glaucoma included in the study. The eye had evidence of progressive optic disc change on stereophotographs (superior and inferior rim thinning) but still presented with visual fields that were statistically within normal limits. Results of the spectral domain optical coherence tomography examination show pronounced retinal nerve fiber layer (RNFL) thinning with an average thickness of 68 μm, compatible with the changes seen on optic disc photographs. The combined index of structure and function (CSFI) was 39%, indicating a loss of 39% of retinal ganglion cells compared with the age-expected number. ASB indicates apostilbs; GHT, glaucoma hemifield test; MD, mean deviation; PSD, pattern standard deviation; SITA Standard-24, Swedish Interactive Threshold Algorithm; TSNIT, temporal-superior-nasal-inferior-temporal; and VFI, visual field index.

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Figure 8. Two eyes with advanced glaucoma (A and B). The superior one shows a mean deviation (MD) of −15.12 dB (A), and the inferior one, MD of −23.61 dB (B). Despite the important differences in visual field damage between the 2 cases, the spectral domain optical coherence tomography results were similar in the 2 eyes, with the same value of average retinal nerve fiber layer (RNFL) thickness of 50 μm. The combined index of structure and function (CSFI) shows markedly different results between the eyes, with values of 74% for the former and 85% for the latter. ASB indicates apostilbs; GHT, glaucoma hemifield test; MD, mean deviation; PSD, pattern standard deviation; SITA Standard-24, Swedish Interactive Threshold Algorithm; TSNIT, temporal-superior-nasal-inferior-temporal; and VFI, visual field index.

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