Abstract: Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the disease. In this meta-analysis, we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to differentiate between Alzheimer’s disease and control subjects. Scientific databases including Google Scholar, Web of Science, and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control subjects. Seventy-three studies (5850 participants, including 2249 Alzheimer’s disease patients and 3601 controls) were included in this meta-analysis. Relative to controls, Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness (standardized mean difference [SMD] = –0.79, 95% confidence intervals [CI]: –1.03 to –0.54, P < 0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus controls. Regarding macular parameters, values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness (pooled SMD: –0.44, 95% CI: –0.67 to –0.20, P = 0.0003), foveal thickness (pooled SMD = –0.39, 95% CI: –0.58 to –0.19, P < 0.0001), ganglion cell inner plexiform layer  (SMD = –1.26, 95% CI: –2.24 to –0.27, P = 0.01) and macular volume (pooled SMD = –0.41, 95% CI –0.76 to –0.07, P = 0.02). Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and controls. Superficial vessel density (pooled SMD = –0.42, 95% CI: –0.68 to –0.17, P = 0.0001) and deep vessel density (pooled SMD = –0.46, 95% CI: –0.75 to –0.18, P = 0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone (SMD = 0.84, 95% CI: 0.17–1.51, P = 0.01) was larger in controls. Vascular density and thickness of various retinal layers were decreased in Alzheimer’s disease patients compared to controls. Our results provide evidence for optical coherence tomography technology having the potential to detect retinal and microvascular changes in patients diagnosed with Alzheimer’s disease and aid in monitoring and early diagnosis methods. 

Key words: Alzheimer’s disease, foveal avascular zone, macular thickness, optical coherence tomography, optical coherence tomography angiography,  , retina, retinal nerve fiber layer, vessel density