Evaluation of a Method for Estimating Retinal Ganglion Cell Counts Using Visual Fields and Optical Coherence Tomography

To evaluate the accuracy and generalizability of a published model that derives estimates of retinal ganglion cell (RGC) counts and relates structural and functional changes due to glaucoma. Both the Harwerth et al. nonlinear model (H-NLM) and the Hood and Kardon linear model (HK-LM) were applied to an independent dataset of frequency-domain optical coherence tomography and visual fields, consisting of 48 eyes of 48 healthy controls, 100 eyes of 77 glaucoma patients and suspects, and 18 eyes of 14 nonarteritic anterior ischemic optic neuropathy (ION) patients with severe vision loss. Using the coefficient of determination R2, the models were compared while keeping constant the topographic maps, specifically a map by Garway-Heath et al. and a separate map by Harwerth et al., which relate sensitivity test stimulus locations to corresponding regions around the optic disc. Additionally, simulations were used to evaluate the assumptions of the H-NLM. Although the predictions of the HK-LM with the anatomically-derived Garway-Heath et al. map were reasonably good (R2 = 0.31-0.64), the predictions of the H-NLM were poor (R2 < 0) regardless of the map used. Furthermore, simulations of the H-NLM yielded results that differed substantially from RGC estimates based on histology from human subjects. Finally, the value-added of factors increasing the relative complexity of the H-NLM, such as assumptions regarding age- and stage-dependent corrections to structural measures, was unclear. Several of the assumptions underlying the H-NLM should be revisited. Studies and models relying on the RGC estimates of the H-NLM should be interpreted with caution.