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Tools & Techniques Diagnostics & prognostics, Neurological

Seeing is Believing

The connection between retinal physiology and broader brain health has gained significant traction in recent years (1). Demands from clinicians for earlier diagnosis of Alzheimer’s disease has been a clear driver in this regard (2) – but finding new detection modalities has proven both scientifically and clinically challenging.  Now, a group of researchers at the Duke University School of Medicine, North Carolina, have shared an approach that is able to differentiate between blood vessel physiology in patients with Alzheimer’s disease, those with mild cognitive impairment, and healthy controls (3).

Dilraj Grewal, Associate Professor of Ophthalmology at Duke University School of Medicine, is one of the lead authors of the study. “In theory, at least, because the retina is an extension of the brain, changes in the density of its blood vessels could provide an indication of broader vascular health in the brain,” he says. “Others have shown that there are changes in the larger blood vessels of the retina in patients with Alzheimer’s (4).” Would the ability to image the smaller vessels enable earlier detection of changes in brain health? To find out, the team used a relatively new imaging technology, called optical coherence tomography angiography (OCT-A), to image the blood vessels of about 5 microns in diameter in the eye – without injecting a dye (5).

 

“We were able to evaluate the differences in the small retinal blood vessels between patients with Alzheimer’s, mild cognitive impairment, and cognitively healthy controls,” says Grewal, who adds that the work has focused on late-stage disease so far. “An extension of our ongoing work will be the ability to detect these changes at an earlier stage, although that possibility is yet to be determined.”

Next, Grewal and the group will pursue two parallel paths forward. “One is to validate retinal imaging as an adjunctive index to existing diagnostic streams,” says Grewal. “The second is to develop and validate the multimodal retinal imaging index as a tool that can be used to monitor change over time. We plan to carry out longitudinal studies to monitor patients and see how the image findings change over time.” But longitudinal studies in an aged population presents an additional challenge. “Many of these patients also have co-morbidities, so being able to follow these patients for long enough to allow evaluation of how these co-morbidities may affect the retinal images and produce meaningful data, is, itself, a significant hurdle,” he says.

In theory, at least, because the retina is an extension of the brain, changes in the density of its blood vessels could provide an indication of broader vascular health in the brain.

And that’s not the only challenge. Scientists and clinicians alike have struggled to pin down early-stage disease manifestation, in part because of a lack of data. A multi-modal approach will be required to solve this problem, says Grewal, who also offers a potential solution. “One way to overcome this issue might be to take pictures of other parts of the eye and combine the various data together,  forming a combined index that doesn’t solely rely on a single imaging modality.”

Moreover, Grewal acknowledges that mild cognitive impairment is a very broad category (6). “It has both amnestic and non-amnestic subtypes – and being able to come up with a threshold to distinguish between the two – and more widely with Alzheimer’s – will be key.”

For now, Grewal and his team remain focused on further developing their approach as a strong adjunctive tool. But, in the future, the multimodal retinal imaging approach could have broader application: “Many neurodegenerative diseases manifest in the retinal tissue and its vasculature,” says Grewal. “We hope to look at those conditions as well. There may be potential to apply our tool to a whole spectrum of neurodegenerative diseases.”

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  1. M Haan et al., “Cognitive function and retinal and ischemic brain changes”, Neurology, 27, 942–9 (2012). PMID: 22422889.
  2. JKH Lim et al., “The Eye as a Biomarker for Alzheimer’s Disease”, Front Neurosci [published online] (2016). PMID: 27909396.
  3. SP Yoon et al., “Retinal Microvascular and Neurodegenerative Changes in Alzheimer’s Disease and Mild Cognitive Impairment Compared with Control Participants”, Ophthalmology Retina, [Epub ahead of Print] (2019). DOI: doi.org/10.1016/j.oret.2019.02.002
  4. H Liao, Z Zhu and Y Peng., “Potential Utility of Retinal Imaging for Alzheimer’s disease: A Review”, Front Aging Neurosci [published online] (2018). PMID: 29988470.
  5. DS Grewal et al., “Assessment of Differences in Retinal Microvasculature Using OCT Angiography in Alzheimer’s disease: A Twin Discordance Report,” Ophthalmic Surg Lasers Imaging Retina, 49, 440-444 (2018). PMID: 29927472.
  6. S Jongsiriyanyong and P Limpawattana, “Mild Cognitive Impairment in Clinical Practice: A Review”, Am J Alzheimers Dis Other Demen, 33, 500–7 (2018). PMID: 30068225.

About the Author

Jonathan James

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