From an optometrist to a cardiologist

A biomarker of cardiovascular diseases was found in the retina of the eye

Maria Azarova, Naked Science

Cardiovascular diseases are the main cause of death and disability worldwide. However, patients at increased risk of developing heart disease can avoid them by changing their lifestyle in time and taking appropriate medications. Alas, in most cases, pathologies remain undetected until a myocardial infarction or stroke occurs.

Therefore, it is important to identify biomarkers that would help identify patients with hidden cardiovascular diseases. People exposed to them are known to be prone to vascular occlusion (impaired patency) of the retina – a multi-layered nervous tissue with a complex capillary network. The superficial and deep vascular plexuses provide oxygen to the inner and middle parts of the retina, while the outer layer receives oxygen from the choriocapillaries. With severe vascular occlusion, the two inner layers of this sensory membrane of the eye atrophy, and with retinal microinfarctions, such as paracentral acute median maculopathy, the middle layer is selectively affected. 

Using non-invasive imaging technology with submillimeter resolution in vivo and optical coherence tomography, it is possible to detect anomalies in retinal images indicating ischemia: in the acute phase, they manifest as a hyperreflective perivenular band at the level of the inner nuclear layer of the retina. Such lesions occur as a result of hypoperfusion or microembolism such as occlusion of the artery and vein of the retina, hypertension, Purcher retinopathy and sickle cell anemia. Visualization of microvessels demonstrates voids of the blood flow signal in the acute phase, which further confirms the ischemic nature of the above disorders. 

The authors of the new study – doctors from the University of California at San Diego (USA) - tried to find out whether such eye lesions are common in patients with cardiovascular diseases and whether it is possible to predict them in this way. The article was published in the journal EClinicalMedicine (Long et al., Prevention of subclinical retinal ischemia in patients with cardiovascular disease – a hypothesis driven study).

"Eyes are a window into our health, many diseases can manifest themselves in them. And cardiovascular diseases are no exception,“ said Mathieu Bahum, who led the research group, ”Ischemia, that is, a decrease in blood flow caused by heart disease, can lead to insufficient blood flow to the eye and lead to the death of retinal cells, leaving behind stable "marks". We called them ischemic perivascular retinal lesions, or RIPLs, and sought to determine whether they could serve as a biomarker of cardiovascular diseases."

Doctors studied the records of 13,940 people who underwent OCT scanning (optical coherence tomography) of the macula - the place of the greatest visual acuity in the retina of the eye – at the University of California at San Diego for various clinical indications from July 1, 2014 to July 1, 2019. After analyzing the medical records, the researchers divided the patients into two groups: the first included 84 people with documented cardiovascular diseases, the second - 76 healthy (that is, who did not have coronary heart disease, strokes, heart failure, atrial fibrillation, hypertension, diabetes mellitus of both types, chronic obstructive pulmonary disease or pulmonary hypertension). In addition, none of the participants were found to have concomitant retinal pathologies.

RIPL – biomarkers of retinal ischemia.  A) Optical coherence tomography of the spectral region; b-scanning showing an optical vertical section of the normal eye); RNFL – retinal nerve fiber layer; GCL – ganglion cell layer; – inner nuclear layer; ONL – outer nuclear layer; RPE – retinal pigment epithelium.
  C) SD-OCT b-scan showing RIPL (red rectangle).
 There is a noticeable focal contraction of INL (red arrow), accompanied by a compensating upward expansion of the darker outer nuclear layer (yellow line).  C) a full-face view recovered from a three-dimensional volumetric scan collected from consecutive b-scans.
 Three RIPLS look like dark dots (red arrows) © EClinicalMedicine

It is known that the risk of cardiovascular diseases in the United States is determined using a special ASCVD calculator developed by the American College of Cardiology. The authors of the study found a correlation between the number of retinal lesions (RIPL) and the risk score calculated by ASCVD for all volunteers.

"Patients with low and borderline ASCVD had a small amount of RIPL in their eyes, but as the risk of ASCVD increased, the amount of RIPL increased. <...> The total number of RIPLS per patient was significantly higher in the group with cardiovascular diseases compared to the control group (2.8 vs. 0.8). The number of RIPLS in people with coronary heart disease and stroke was 2.4 and 3.7. In patients with myocardial infarction, the RIPL index was 3-4 – compared with 1.3 RIPLS in patients with coronary heart disease without a heart attack. <...> We noticed the most retinal lesions in patients who had suffered a stroke. Since the retina is a direct extension of the brain, it is more likely that RIPLs talk about cerebral disease than about coronary vascular diseases," the researchers said.

Thus, the results confirmed that retinal lesions – biomarkers of previous ischemic infarcts of this inner shell of the eye – are common in patients with cardiovascular diseases and can serve as an additional sign for their prediction and detection. According to the authors of the work, if an ophthalmologist detects RIPL in a patient, then he should be referred to a cardiologist for an appointment.

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