Commentary
Video
Assessing Clinical Relevancy of Visual Biomarkers in Alzheimer Disease: Alfredo A. Sadun, MD, PhD
The chief of ophthalmology at the Doheny Eye Institute discussed decades of research uncovering how Alzheimer can impact visual function and how retinal imaging may advance diagnosis. [WATCH TIME: 13 minutes]
WATCH TIME: 13 minutes
"We found out that patients [with Alzheimer] do not suffer a loss of acuity nor color vision, but they do suffer losses of stereo, and most of all, contrast sensitivity and orientation. They don’t know where things are, and that interferes with their further ability to use their eyes in an effective way.”
The retina has been gaining recognition as a promising site for noninvasive diagnosis and monitoring of Alzheimer disease (AD), with studies showing that key pathological features such as amyloid-β deposits, abnormal tau, vascular changes, inflammation, and neurodegeneration can be present in both the retina and brain of patients with the disease. Overall, these parallels suggest a strong correlation between retinal and cerebral pathology. Advanced imaging technologies like optical coherence tomography (OCT), OCT-angiography, and confocal scanning laser ophthalmoscopy have allowed for the detection of these changes in patients, offering potential tools for early screening and disease tracking; however, further large-scale, biomarker-confirmed studies may be needed to validate retinal biomarkers and standardize imaging protocols.1
Building on the growing evidence that retinal changes mirror brain pathology in AD, previous research has mapped the specific nature and distribution of AD-related abnormalities in the retina. A detailed analysis of postmortem retina and brain tissues from 86 donors revealed that patients with mild cognitive impairment (MCI) and AD show increased levels of amyloid-β forms and novel intracellular Aβ oligomers, particularly in the inner and peripheral retinal layers. These findings were linked to heightened glial activation, tissue atrophy, and diminished microglial clearance activity, especially in women. This study further supported the retina’s potential as a noninvasive window into AD progression and a promising source of quantifiable biomarkers for early detection and disease monitoring.2
Adding a clinical perspective to these findings, Alfredo A. Sadun, MD, PhD, chief of ophthalmology at the Doheny Eye Institute, spoke with NeurologyLive® about his decades-long investigation into the visual manifestations of AD. In the interview, Sadun recounted his early histopathologic work identifying optic nerve fiber degeneration in AD, long before the field widely accepted a retinal connection. He described how evolving imaging tools, particularly OCT, helped confirm and build upon those initial discoveries. His observations of impaired contrast sensitivity, orientation, and eye movement in patients further underscored the retina’s role in AD pathophysiology. Looking ahead, Sadun emphasized that technologies like OCT and others may offer noninvasive, quantifiable biomarkers to aid in both diagnosing AD and tracking its progression over time.
