Can the Eye Reveal Cardiac and Lung Disease — Plus Much More?

Thinner retinal layers were associated with a long list of major diseases, including pulmonary and cardiac disorders, according to a phenotypic and genomic analysis.

Among the many diseases, each standard deviation of thinner photoreceptor segment layers was significantly associated with risks for:

• Nonhypertensive congestive heart failure: HR 1.25 (95% CI 1.12-1.39)
• Incident chronic airway obstruction: HR 1.31 (95% CI 1.24-1.38)
• Myocardial infarction: HR 1.17 (95% CI 1.10-1.25)
• Emphysema: HR 1.47 (95% CI 1.30-1.65)

Notably, those with existing prevalent multiple sclerosis had significantly thinner ganglion cell complex layers (β = -1.12, 95% CI -1.37 to -0.87), as did those with alcoholic liver damage (β = -0.68, 95% CI -0.98 to -0.38), reported Nazlee Zebardast, MD, MSc, of Harvard Medical School in Boston, and colleagues in Science Translational Medicine.

After adjustments for various confounders, thinner photoreceptor segments at baseline were associated with mortality over a 10-year follow-up period (HR 1.16, 95% CI 1.11-1.22), as were baseline thinner ganglion cell complex layers (HR 1.12, 95% CI 1.07-1.18).

The findings don’t definitively prove that there’s a direct connection between thinner retinal layers and disease. In addition, the clinical importance of the results is unclear. However, the study does shed more light on the connections between retinal and systemic health, a topic that scientists have been trying to better understand.

“We’ve come to realize recently that there is a lot more information that we can get from our retina images than we thought was possible,” said Zebardast in a press statement. “This could potentially help with disease prevention. If we know from someone’s retinal image that they are at high risk of developing glaucoma or cardiovascular disease in the future, we could refer them for follow-up screening or preventative treatment.”

Zebardast told MedPage Today that previous research has linked retinal phenotypes to cardiovascular health and factors related to systemic aging. “In this work, we went a step further to differentiate the nine different retinal layers, which each reflect different cell types in the retina that play different functional roles. These include different types of neuronal cells, vascular cells, and epithelial cells.”

In an interview, study co-author Saman Doroodgar Jorshery, MD, MPH, a postdoctoral fellow at Harvard Medical School, said the working theory is that thinner retinal layers represent the effects of disease.

Poor heart and lung function, for example, seem likely to thin photoreceptor segments by impairing blood flow to the cells within them, he said. “Photoreceptor cells are very vulnerable and can be easily damaged with hypoxemia and blood flow limitations, which are often secondary to cardiovascular or pulmonary disease.”

As for multiple sclerosis, epilepsy, and alcohol use disorder, he said they can cause damage to retinal nerve fiber layers. In addition, “optic neuropathies can be secondary to substance use and lead to nerve degeneration and atrophy across the retina over time, thereby leading to thinning of the retinal inner layer.”

Pearse Keane, MD, MSc, of Moorfields Eye Hospital in London, told MedPage Today that the new findings build on rapidly expanding knowledge about the links between eye health and systemic health. Advanced retinal imaging, big data, and artificial intelligence have “supercharged” research into potential connections, and the emerging field is now known as “oculomics,” he said.

“In many respects it makes sense that the eye can provide this window,” said Keane, who studies links between eye health and non-ocular disease, but wasn’t involved with the new research. “The microvasculature of the retina is the only such circulation that can be directly visualized in living human subjects. And the neural tissue of the retina is a direct outpouching of the central nervous system.”

Keane said Zebardast and colleagues “effectively provide a treasure map for the field of oculomics to further explore.”

However, “we need to be cautious as some associations may be due to confounding factors,” he added. “For example, previous work from my group has shown changes in the retina in patients with schizophrenia. However, these changes may be related to the medications used to treat the condition or due to secondary cardiometabolic effects of the condition.”

For the study, Zebardast and team used optical coherence tomography (OCT) images to analyze retinal layer thicknesses in 44,823 participants in the U.K. Biobank. Mean age was 56.8 years, 53.7% were women, and all were of European descent.

The researchers found that thinner photoreceptor segments were also linked to several other conditions such as ischemic heart disease; cardiac conduction disorders; type 1 and type 2 diabetes; ophthalmic and neurological manifestations of diabetes; pneumonia; chronic bronchitis; and elevated HbA1c, resting heart rate, and serum triglycerides.

“Further research is warranted to quantify the value of retinal OCT measurements used independently or in combination with existing risk assessment methods,” the authors wrote. “Furthermore, our study highlights how retinal imaging may be integrated with electronic health records, genomic data, and other biomarkers to advance our understanding of disease mechanisms and help inform risk prediction and risk modification strategies.”

Zebardast wasn’t sure about the cost of OCT technology. However, “once you have an OCT machine, theoretically you could do endless scans without any additional price added, and a single scan with an OCT takes less than 1 minute. It’s not like a CT or MRI scan, which requires a big machine and power, etc.”

What’s next? While it’s still early, Keane said “we hope we may be able to identify people with these conditions directly from their retinal images. This could help identify people for further diagnostic testing or for clinical trials. We might even be able to predict the future development of some conditions.”

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