March 1, 2024

Predicting Disease with Retinal Imaging and Genetics

A study by researchers at Mass Eye and Ear and the Broad Institute revealed that retinal imaging combined with genetic analysis can predict the risk of developing ocular and systemic diseases. Credit: SciTechDaily.com

  • Mass Eye and Ear physician-researchers show that retinal imaging can help predict a person’s risk of developing eye, neuropsychiatric, heart, metabolic and lung diseases.
  • The team also identified genetic loci associated with retinal thinning, which could help develop personalized treatment plans and future therapies for eye diseases such as glaucoma and macular degeneration.

The retina is said to provide a window into a person’s systemic health. In a new study published on January 24th in Scientific Translational Medicinemedical researchers at Mass Eye and Ear, a member of Mass General Brigham and the Broad Institute of Nazlee Zebardast

Study senior author Nazlee Zebardast, MD, MSc, director of Glaucoma Imaging at Mass Eye and Ear, examines OCT images. Credit: Mass Eye and Ear

Linking retinal health to systemic conditions

Previous studies have shown that there are links between retinal health and health conditions including aging, cardiometabolic diseases such as diabetes and hypertension, and neurological diseases such as dementia, stroke and multiple sclerosis.

“We recently realized that we can get much more information from our retinal images than we thought possible,” says senior author Nazlee Zebardast, MD, MSc, director of Glaucoma Imaging at Mass Eye and Ear and assistant professor of ophthalmology at Harvard Medical School. . “It is really exciting to be able to see that these images, obtained without the need for any type of invasive procedure, are associated with so many systemic conditions, both at a genetic and epidemiological level.”

To identify associations between retinal health and disease risk, and to identify genes associated with retinal health, researchers analyzed data from 44,823 UK Biobank participants who underwent retinal optical coherence tomography (OCT), genotyping and baseline health measurements in 2010. and were then followed for disease development for an average of ten years.

Seyedeh Maryam Zekavat and Saman Doroodgar Jorshery

Study co-authors Dr. Seyedeh Maryam Zekavat and Saman Doroodgar Jorshery examine retinal thickness data and images. Credit: Mass Eye and Ear

Insights into retinal layers and genetic associations

Unlike previous studies that looked for genes associated with overall retinal health, this study delved deeper into the role of the different cell layers that make up the retina.

“Each layer of the retina is composed of different cell types with diverse structures and functions, and we show that the thicknesses of these different layers are associated with different conditions,” says Zebardast, who is also an associate scientist at Broad.

The study also provides information about the genes and biological pathways that determine retinal health, which could be leveraged to develop future therapies, the researchers say. In total, the team identified 259 genetic loci associated with retinal thickness.

A particular insight from this work was that multiple systemic health conditions, including poor heart, metabolic, lung and kidney function, are linked to thinning of the photoreceptor segment of the retina, although more research is needed to confirm causality. Future studies should also aim to replicate the study methods in more diverse populations and across different age groups, as UK BioBank participants were predominantly white and aged between 40 and 70 years at the start of the study.

Expanding Clinical Applications and Future Directions

The study is part of an ongoing effort by Mass Eye and Ear to identify genetic markers of glaucoma and other eye diseases that can help develop personalized risk scores and treatment plans for patients. OCT imaging of the retina is already a standard clinical procedure in ophthalmology at Mass Eye and Ear and elsewhere, but the authors say their results suggest its use could be expanded. New work on the link between ocular and cardiometabolic health will provide insight into its clinical utility, and researchers are expanding this line of research with co-author Pradeep Natarajan, MD, director of preventive cardiology at Massachusetts General Hospital, and associate member . at the Broad Cardiovascular Disease Initiative.

Conclusion: The potential of retinal imaging in predicting health

“Patients come to us for eye health, but what if we could tell them more than that?” says Zebardast. “What if we could use images of someone’s retina to say, ‘You seem to be at high risk for high blood pressure, maybe you should get tested, or maybe your primary care doctor should know this.’”

The authors have developed an online user interface for all their findings in the Ocular Knowledge Portal to allow researchers to explore associations between retinal layer thickness, disease, and genetics.

Reference: “Phenomena and genome-wide analyzes of retinal optical coherence tomography images identify links between ocular and systemic health” by Seyedeh Maryam Zekavat, Saman Doroodgar Jorshery, Franziska G. Rauscher, Katrin Horn, Sayuri Sekimitsu, Satoshi Koyama, Trang T. Nguyen, Maria C. Costanzo, Dongkeun Jang, Noël P. Burtt, Andreas Kühnapfel, Yusrah Shweikh, Yixuan Ye, Vineet Raghu, Hongyu Zhao, Marzyeh Ghassemi, Tobias Elze, Ayellet V. Segrè, Janey L. Wiggs, Lucian Del Priore, Markus Scholz, Jay C. Wang, Pradeep Natarajan, and Nazlee Zebardast, January 24, 2024, Scientific Translational Medicine.
DOI: 10.1126/scitranslmed.adg4517

Authorship: Seyedeh Maryam Zekavat (MEE, MGH, Broad) Saman Doroodgar Jorshery (Broad) Franziska G. Rauscher (Lepzig), Katrin Horn (Leipzig), Sayuri Sekimitsu (Tufts) Satoshi Koyama (MGH, Broad) Trang T. Nguyen (Broad ) Maria C. Costanzo (wide), Dongkeun Jang (wide), Noël P. Burtt (wide), Andreas Kühnapfel (Leipzig) Yusrah Shweikh (MEE), Yixuan Ye (Yale), Vineet Raghu (MGH, wide), Hongyu Zhao (Yale), Marzyeh Ghassemi (Toronto), Tobias Elze (MEE), Ayellet V. Segrè (MEE), Janey L. Wiggs (MEE), Lucian Del Priore (Yale), Markus Scholz (Leipzig), Jay C. Wang ( Yale) Pradeep Natarajan (MGH, Broad) Nazlee Zebardast (MEE, Broad).

Disclosures: Natarajan reports research grants from Allelica, Apple, Amgen, Boston Scientific, Genentech/Roche, and Novartis; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis; scientific advisory board member for Esperion Therapeutics, Preciseli and TenSixteen Bio; scientific co-founder of TenSixteen Bio; equity participation in MyOme, Preciseli and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. Wiggs received financial support from Aerpio and served as a consultant for Allergan, Avellino, Editas, Maze and Regenxbio. Outside of this work, he served as a consultant for Zeiss. There is no conflicting relationship for other authors.

Funding: This study was supported by the National Eye Institute with additional support from the Hassenfeld Scholar Award from Massachusetts General Hospital, grants from the National Heart, Lung, and Blood Institute, and analysis support from the LIFE Leipzig Research Center for Civilization Diseases. A full list of funders can be found in the newspaper.

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