Introduction: Retinal ganglion cell (RGC) degeneration was histopathologically proved previously in Alzheimer's disease (AD) patients. In this study, we aimed to determine RGC degeneration in vivo using optical coherence tomography (OCT) in AD. Methods: Twenty-one mild-to-moderate AD patients and 25 cognitively healthy age-matched controls were enrolled in this case-control prospective study. All participants underwent OCT examination to assess peripapillary retinal nerve fiber layer (RNFL) thickness, macular volume, and thickness. Results: Foveal thickness and volume were significantly higher in AD patients than controls (P = 0.023 and P = 0.024, respectively). Compared to controls, peripapillary RNFL and other macular region measurements of AD patients were not statistically different (for all P > 0.05). Discussion: Increased foveal thickness and volume can be associated with the pathological changes in the early stages of degeneration These results differ from previous studies, but still confirm retinal degeneration in AD. Conclusion: With further OCT studies on large populations, OCT will be in clinical use for early diagnosis of AD.