Purpose:To evaluate the relationship between visual field index (VFI) and the estimated number of retinal ganglion cells (RGCs) in glaucoma.Methods:A multicenter study of 1,245 healthy, glaucomatous and suspected glaucomatous eyes of 1,245 subjects recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). All eyes underwent standard automated perimetry (SAP) and time-domain optical coherence tomography (TD-OCT). Estimates of RGC count and percentage of RGCs remaining, compared to age-matched healthy eyes, were calculated from TD-OCT using a previously described formula. Smoothing spline curves were fitted to examine the relationship between VFI and the percent remaining RGCs. The first derivative (i.e., slopes) of these curves was used to explore the relationship between changes in these measures.Results:The relationships between the VFI and both estimated RGC counts and the percent remaining RGCs were nonlinear. A unit number of VFI loss corresponded to substantially greater loss of estimated RGCs and estimated percentage of RGCs remaining in early compared to late disease.Conclusions:The relationship between VFI and estimated RGC counts is nonlinear and the index substantially underestimates the amount of neural loss early in the disease. Disease severity should be taken into account when interpreting rates of VFI change over time. © 2013 Marvasti et al.