Cerebral Neurodegeneration May be Indicated by Retinal Microvascular Parameters

The eye can serve as a great structure in which to analyze health in other parts of the body. Links between the eye and the brain have been explored and uncovered for many years, with multiple associations having already been established. In a new study published in BMC Ophthalmology, researchers assessed the relationship between retinal and choroidal structural and microvascular parameters as well as brain volumetric MRI parameters in patients with either amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease (AD). Hippocampal volume was negatively correlated with FAZ area in aMCI patients, which could be due to FAZ enlargement contributing to capillary dropout, since the FAZ borders parafoveal capillaries. In turn, this may reflect underlying neurodegenerative changes in response to amyloid-beta deposition within the retinal microvasculature. These images from the study show MRI images and corresponding 3x3mm OCT-A scans of the superficial capillary plexus showing vessel density (VD) and perfusion density (PD) maps of the right eye of two participants, one with Alzheimer’s disease and one with amnestic mild cognitive impairment (MCI). There is reduction in both VD and PD in the patient with AD compared to the patient with amnestic MCI. Photo: Zhao W, et al. BMC Ophthalmol. 2025;25:365. Click image to enlarge. OCT, OCT angiography (OCT-A) and volumetric brain MRI imaging were analyzed in the 68 eyes of 37 aMCI patients and 64 eyes of 33 AD patients. It was found that hippocampal volume negatively correlated with foveal avascular zone (FAZ) area and positively correlated with perfusion and vessel densities in the 3mm OCT-A scan of aMCI patients. Also for these patients, superior and inferior lateral ventricle (SLV; ILV) volumes were inversely correlated with perfusion density in the 3mm and 6mm OCT-A scans, respectively.In patients with AD, both SLV and ILV volumes were inversely correlated with perfusion and vessel densities in the 3mm and 6mm OCT-A scans. However, central subfield thickness, ganglion cell-inner plexiform layer thickness, retinal nerve fiber layer thickness and choroidal vascularity index were all found to have no significant correlation with SLV, ILV or hippocampal volume in any cohort.The authors of the study further discuss their findings and subsequent implications in the discussion of the paper. They mention the finding that, for aMCI patients, SLV volume expansion was linked with decreasing perfusion density in the 3mm circle and ILV volume expansion was linked with decreasing perfusion density in the 6mm inner ring. This reduction, they explain, between retinal perfusion density and ventricular expansion “may reflect an underlying neurodegenerative process affecting both the cerebral and retinal microvasculature and suggests potential of retinal measurements to be used as a surrogate.”As for those in the AD cohort, SLV and ILV volume expansion correlated with decreasing vascular and perfusion densities in both 3mm and 6mm OCT-A scans. The authors elaborate that ventricular expansion in Alzheimer’s is believed to be driven via the medial temporal love and whole brain atrophy. One possible mechanism is pathological accumulation of amyloid-beta plaques in brain tissue and cerebral small vessels, which can be seen in cerebral amyloid angiography. Relating back to the eye, only vascular and perfusion densities, of all OCT and OCT-A parameters, were found to correlate with volumetric MRI parameters, suggesting that OCT-A may be more sensitive to Alzheimer’s related brain atrophy than OCT structural components.Taking these pieces together, the researchers offer that “these findings suggest a pathophysiologic link between retinal microvascular changes and AD-related cerebral neurodegeneration, warranting further investigation into the etiology and implication of these changes.”Click here for the journal source. Zhao W, Robbins CB, Grewal DS, et al. Correlating retinal and choroidal vascular parameters with volumetric MRI in Alzheimer’s disease and amnestic mild cognitive impairment. BMC Ophthalmol. 2025;25:365.