Could studies on retinal imaging biomarkers move from research to clinical use?
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The neurologist’s viewpoint
As a behavioral neurologist specializing in Alzheimer’s disease, I think retinal imaging biomarkers show great promise in aiding clinical diagnosis and as a marker of disease progression.
The retina is a noninvasively accessible outgrowth of the central nervous system that may demonstrate Alzheimer’s pathology either through changes in neuronal layer thickness, deposition of proteins such as amyloid, or alterations in the complexity of vascular connections. Examination of the retina remains a research tool in assessment of cognitive impairment, but evidence is rapidly accumulating supporting its utility and ultimate transition to clinical care. In work with our Duke collaborators, Sharon Fekrat, MD, and Dilraj Grewal, MD, we found that macular vascular density, perfusion density and macular ganglion cell inner plexiform layer thickness are significantly reduced in individuals with Alzheimer’s disease compared with individuals with mild cognitive impairment and normal cognition.
The ease of repeated retinal examination offers a rapid means for measuring change in clinical trials and clinical care, but longitudinal studies linking retinal changes with disease progression are needed. Researchers are also examining whether the retina can be used as a biomarker for other neurodegenerative diseases, such as Parkinson’s disease and frontotemporal dementia. Important questions remain, such as how do other common age-related eye pathologies, for example, macular degeneration and cataracts, influence Alzheimer’s disease-related retinal changes. Additional research is also needed on common comorbid conditions (smoking, diabetes, stroke and cardiovascular disease) that can have an impact on the retina and could obscure Alzheimer’s retinal changes.
Despite these caveats, retinal imaging may offer advantages, including a rapid screening method for Alzheimer’s that bypasses more expensive or invasive procedures such as MRI or cerebrospinal fluid examination for amyloid and tau.
James R. Burke, MD, PhD, is with the department of neurology at Duke University Medical Center in Durham, North Carolina.
The cardiologist’s viewpoint
Retinal imaging holds the potential for easier, less invasive, more accessible and more affordable screening of patients at risk for cardiovascular disease.
It offers an opportunity to bring the testing away from laboratories and hospitals to primary care centers, where it could be handled by general practitioners at a cost that is a fraction of that of a CT scan, an MRI or an echo machine. A CT scan, depending on the country where it is performed, may cost from a few hundred to a few thousand dollars, it is not easily accessible, people may have to travel, and there is radiation, as well as injection of intravenous contrast. Nuclear stress testing has similar downsides, and stress echocardiography is a highly operator-dependent test. With retinal imaging, the equation changes quite a lot.
However, I don’t believe in screening just because we have a tool, and we must choose the right patients to screen, those in which earlier interventions might make a difference. For instance, in patients with high cholesterol, a screening test might help determine who should be given statin therapy, whereas low-risk patients with borderline cholesterol may not need to have a screening test. Potentially, we could consider this method also in the evaluation of cardiac fitness for surgery, but again, there are important distinctions to be made. If a high-risk patient is going for a high-risk operation, then we may need more specific tests. But if we are dealing with a low-risk patient going for a low-risk procedure, a cardiac test may not be needed. For a moderate-risk patient, perhaps a less invasive measure such as retinal imaging may play a role. A lot depends on the specific use. I would not use retinal screening for the purpose of evaluating a 70-year-old smoker with chest pain because it is not intended as a diagnostic tool. We also need to understand how to interpret retinal vascular features in patients with more than one disease condition, such as diabetes, hypertension and chronic kidney disease.
Lastly, we need to know if these retinal images change with time or change with treatment of the underlying heart disease. If we lower the cholesterol level in a patient and modify the cardiac risk for the future, would that change the retinal image? Is there any value in sequential retinal images when a patient has had treatment? Many questions remain open in the arena, and we need further research. There are exciting times on the horizon.
Khung Keong Yeo, MD, is with the department of cardiology at the National Heart Centre Singapore.
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