Association between retinal neurodegeneration assessed by optical coherence tomography and PET-detected cerebral amyloid burden in Alzheimer's disease: A systematic review

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BackgroundRetinal imaging is proposed as a biomarker for Alzheimer's disease, but evidence linking retinal changes to cerebral amyloid remains inconsistent, particularly in preclinical populations.ObjectiveThis article evaluates whether retinal structural and microvascular changes measured by optical coherence tomography (OCT) and OCT-angiography (OCT-A) are associated with cerebral amyloid-β (Aβ) burden assessed by positron emission tomography (PET).MethodsPubMed, Embase, Scopus, and Web of Science were searched on November 10, 2025. Two reviewers independently did screening, extraction, and quality assessment. Extracted outcomes included macular and peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness, vessel density, foveal avascular zone size, and PET tracers.ResultsTwenty-two studies including 1616 participants met inclusion criteria. Fifteen assessed OCT, five OCT-A, and two both. Among cognitively normal individuals, seven studies compared retinal nerve fiber layer thickness by Aβ status, with only one reporting a significant difference. Overall, OCT metrics showed no consistent differences by Aβ status. OCT-A results were similarly inconsistent, with one study linking larger foveal avascular zone to Aβ positivity. Substantial heterogeneity in imaging devices, segmentation methods, and PET quantification was observed, and few studies adjusted for these factors.ConclusionsCurrent evidence does not demonstrate a consistent relationship between retinal OCT or OCT-A metrics and cerebral Aβ burden measured by PET. Methodological heterogeneity, small sample sizes, and limited statistical rigor contribute to inconclusive results. Standardized imaging protocols and longitudinal studies are required to determine whether retinal imaging can serve as a reliable non-invasive biomarker for early Alzheimer's disease.

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