The Eyes as a Gateway to Multiple Diseases

Researchers have discovered that the eyes can offer insights into various diseases, associating thinner retinal layers with genetic factors and linking them to ocular, cardiometabolic, and neuropsychiatric conditions.

The study proposes the potential development of markers for both systemic and ocular health using optical coherence tomography (OCT), a technique routinely employed for obtaining 3D eye images requiring minimal training.

Published in the journal Science Translational Medicine, the findings underscore the integration of retinal imaging with electronic health records, genomic data, and other biomarkers to enhance our comprehension of disease mechanisms. This integration can also contribute to refining risk prediction and modification strategies, as reported by Seyedeh Maryam Zekavat and colleagues from the Massachusetts Eye and Ear Infirmary.

Previous research has linked changes in retinal thickness to systemic diseases. In this study, Zekavat and her team examined retinal images from 44,823 participants in the UK Biobank using OCT. They explored the correlation between the thickness of nine retinal layers and various incident conditions, quantitative traits, blood biomarkers, and over 13 million genetic variants.

By conducting OCT layer cross-phenotype and genome-wide association analyses, the researchers identified associations between different retinal layers and specific phenotypes, uncovering the genetic variants influencing these layers. Genome-wide association studies pinpointed inherited genetic markers affecting retinal layer thicknesses, a discovery validated among 6,313 individuals in the LIFE-Adult study. In total, 259 loci were linked with retinal layer thickness.

Over a median 10-year follow-up, the team established connections between retinal layer thickness and the onset of ocular, neuropsychiatric, and cardiometabolic diseases.

Retinal layer thickness demonstrated an association with incident mortality over the ten-year follow-up, particularly pronounced in individuals with thinner photoreceptor segment layers and thinner ganglion cell complex (GCC) layers, even after adjusting for various sociodemographic factors.

The consistency observed between epidemiologic and genetic associations suggested a correlation between the thickness of specific retinal layers, as assessed using optical coherence tomography (OCT), and distinct ocular and systemic conditions.

For instance, thinner layers of photoreceptor segments (PSs) were correlated with age-related macular degeneration, as well as compromised cardiometabolic and pulmonary function. Additionally, a thinner retinal nerve fiber layer (RNFL) was linked to glaucoma.

In terms of incident cardiometabolic diseases, each standard deviation in thinner PS layer was significantly associated with the risk of future incidents such as hypertension (Hazard Ratio [HR]=1.09), hypercholesterolemia (HR=1.10), myocardial infarction (HR=1.17), nonhypertensive congestive heart failure (HR=1.25), cerebrovascular disease (HR=1.15), peripheral vascular disease (HR=1.32), and abdominal aortic aneurysms (HR=1.47).

The authors emphasized that thinning in various retinal layers was associated with an increased risk of future circulatory diseases, including the GCC for aortic aneurysms and congestive heart failure, RNFL for hypertension, heart failure, cerebrovascular disease, and paroxysmal supraventricular tachycardia, and the choroid-scleral interface for ischemic heart disease and hypertrophic cardiomyopathy.