Retinal Microstructural and Microvascular Changes in Alzheimer Disease: A Review

"The eyes are a window to the brain," prompting the investigation of whether retinal biomarkers can indicate Alzheimer disease (AD) and cognitive impairment. AD is a neurodegenerative condition with a lengthy preclinical phase where pathologic changes in the central nervous system (CNS) occur before clinical symptoms. Mild cognitive impairment (MCI) often precedes AD. As part of the CNS, the retina exhibits similar pathologic changes related to AD as those seen in the brains of patients with MCI. Noninvasive imaging technologies such as optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) allow high-resolution visualization of the retina, providing an opportunity to screen and monitor AD noninvasively. In this review, we summarize the relationship between AD and retinal pathology detected by OCT and OCTA. The most common findings in patients with AD include peripapillary retinal nerve fiber layer thinning, decreased macular thickness, an enlarged foveal avascular zone, and decreased vascular densities in the superficial and deep capillary plexuses. These retinal changes correlate with magnetic resonance imaging (MRI) findings of cerebral atrophy, positron emission tomography (PET) findings of increased amyloid load, and neuropsychological testing results suggesting cognitive dysfunction. We conclude that retinal microstructural and microvascular abnormalities may serve as biomarkers for the early detection and clinical monitoring of AD and as tools for evaluating potential treatment effects. Future studies should focus on standardizing protocols for in vivo ophthalmic imaging to measure retinal pathology in AD and MCI.