Retinal Changes on OCT Angiography May Flag Early Alzheimer's

Damian McNamara

May 08, 2018

LOS ANGELES —  Microvascular changes in the retina detected by using noninvasive optical coherence tomography (OCT) angiography align well with imaging and biomarker evidence of preclinical Alzheimer's disease, a new study shows.

The technology detected a significantly larger foveal avascular zone among 14 participants with biomarker-positive positron emission tomography (PET) imaging compared with 16 other people without this preclinical sign of Alzheimer's (0.30 mm2 vs 0.40 mm2; P = .002).

PET biomarker–positive patients (essentially patients with preclinical Alzheimer's disease), had "a significantly increased size of the foveal avascular zone. It was robustly positive," Gregory Van Stavern, MD, a neurologist at Washington University School of Medicine in St. Louis, Missouri, said here at the American Academy of Neurology (AAN) 2018 Annual Meeting.

"Changes in the visual system, and the eye itself, can parallel changes in the brain, and are more easily detected with some of the tools we use every day in clinic," Van Stavern told Medscape Medical News.

The researchers arrived at a similar finding by examining cerebrospinal fluid biomarkers associated with Alzheimer's disease. For example, inner foveal thickness was thinner among the cerebrospinal fluid  (CSF) biomarker–positive patients (75.4 μm vs 66 μm; P = .278) compared with the others.

It is now possible to identify the pathology of Alzheimer's disease by using biomarkers on PET imaging with Pittsburgh compound B or florbetapir radiotracers, Van Stavern said. Amyloid β-42 peptide or tau protein levels can also indicate Alzheimer's disease.

"It's also become clear that the pathology of Alzheimer's disease can appear decades before the onset of cognitive decline," he added. Although it is possible to identify people who are at risk for Alzheimer's disease by using PET or amyloid data, "unfortunately, both these modalities are expensive, time-consuming and cumbersome."

OCT angiography is OCT with super-high-speed scanning. "Essentially what this does is separate out objects in the retina that are stationary from objects in motion. It separates out blood cells and produces these really nice vascular maps of the retina and the optic nerve" without use of dye, he said.

Previous research associates microvascular changes in the eyes, especially loss of ganglion cells and axons in the retina, with risk for Alzheimer's disease and among people with established disease. Retinal thinning on OCT was associated with cognitive decline in one study, for example, and fundus photography offered another window into these structural eye changes in another.

The 30 participants in this case-controlled, single-center study underwent PET amyloid imaging or CSF analysis. The healthy volunteers had no cognitive dysfunction at baseline, based on a 0 score on the Clinical Dementia Ratio Scale. The investigators controlled for patient age and intraocular pressure in their analysis.

Using OCT angiography (AngioVueHD, Optovue Inc), Van Stavern and colleagues measured the thickness of the retinal nerve fiber layer, ganglion cell layer, and fovea (inner, outer, and total). They also assessed macular volume, the foveal avascular zone, and the vascular volumes of the macula, fovea, and parafoveal regions.

"It's a small sample, but ultimately we found that subjects who were biomarker positive — essentially in the preclinical Alzheimer's disease state — had foveal thinning, which is congruent with the overall literature in established Alzheimer's disease," he said. "We also found that the biomarker-positive subjects also had enlargement of the foveal avascular zone." He added, "The mechanism for this result is still not entirely clear."

The evidence is not yet sufficient to permit recommendation of OCT angiography for routine Alzheimer's disease screening in a clinical setting, he said. "We need more data over a longer timeframe. However, our early results suggest that this might be possible down the line."

"Honestly, this is really where the field is headed — to identify people in the preclinical stage before there is too much neuronal and axonal loss," he said.

In the future, Van Stavern would like to do a longitudinal analysis to expand on the current findings. He plans to continue recruiting cognitively healthy individuals, as well as people with early and advanced Alzheimer's disease.

Asked to comment on the findings by Medscape Medical News, Joel S. Schuman, MD, chair of ophthalmology at New York University Langone Medical Center and professor of neuroscience and physiology at the NYU School of Medicine in New York City, pointed out that the researchers show a large foveal avascular zone and a thin fovea in cognitively healthy individuals with biomarkers positive for Alzheimer's disease.

"These findings are interesting and potentially valuable in early detection of AD, and in noninvasively adding certainty to the diagnosis," he added. "Potential confounders, such as age, coexisting diseases, and presence of maculopathies, will need to be considered in the development and interpretation of this work."

An educational grant from Optovue Inc supported this research. Van Stavern and Schuman have disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2018 Annual Meeting. Abstract S16.001. Presented April 23, 2018.

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