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. ©2012 American Medical Association. All rights reserved.