Close up photo of a woman's eye to symbolize inherited eye diseases
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Researchers have found that the eye can provide a window into many different diseases, with thinner retinal layers having a genetic basis and an association with ocular and cardiometabolic diseases as well as neuropsychiatric conditions.

The findings suggest that markers for systemic and ocular health could be developed from optical coherence tomography (OCT), which is routinely used for obtaining 3D images of the eye that requires minimal training.

The results appear in the journal Science Translational Medicine.

“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,” report Seyedeh Maryam Zekavat, from Massachusetts Eye and Ear Infirmary, and colleagues.

Changes in retinal thickness have previously been linked with systemic disease.

In the current study, Zekavat and co-workers studied retinal images captured from 44,823 participants in the UK Biobank using OCT.

They then studied the relationship between the thickness of nine retinal layers and 1866 incident conditions, 88 quantitative traits and blood biomarkers, and over 13 million genetic variants.

Specifically, the researchers performed OCT layer cross-phenotype and genome-wide association analyses to identify which phenotypes were associated with the different layers of the retina, and what genetic variants influenced these layers.

A schematic showing the structure of the retina and measurements of the thickness of 9 different retinal layers with retinal OCT imaging data available in the UK Biobank (N=44,823).
A schematic showing the structure of the retina and measurements of the thickness of 9 different retinal layers with retinal OCT imaging data available in the UK Biobank (N=44,823) [Zekavat et al., Sci. Transl. Med. 16, eadg4517 (2024)]
Genome-wide association studies identified inherited genetic markers influencing retinal layer thicknesses, which were replicated among 6313 individuals in the LIFE-Adult study.

Overall, 259 loci were linked with retinal layer thickness.

During a median of 10 years of follow up, the team identified links between retinal layer thickness and incident ocular, neuropsychiatric, and cardiometabolic diseases.

Retinal layer thickness was associated with incident mortality during the decade of follow up and was greatest among individuals with thinner photoreceptor segment layers and thinner ganglion cell complex (GCC) layers, after adjusting for multiple sociodemographic factors.

Consistency between epidemiologic and genetic associations indicated a relationship between the thickness of particular retinal layers assessed using OCT and particular ocular and systemic conditions.

For example, thinner layers of photoreceptor segments (PSs) were linked with age-related macular degeneration, and both poorer cardiometabolic and pulmonary function.

There were also links between a thinner retinal nerve fiber layer (RNFL) and glaucoma.

Among incident cardiometabolic diseases, each standard deviation in thinner PS layer was significantly associated with the risk of future incident 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 add: “Other retinal layers where thinning was associated with increased risk of future circulatory disease included GCC for aortic aneurysms and congestive heart failure, RNFL for hypertension, heart failure, cerebrovascular disease, and paroxysmal supraventricular tachycardia, and [choroid-scleral interface] for ischemic heart disease and hypertrophic cardiomyopathy.”

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