Findings may lead to earlier diagnoses and better prognostic information for patients — and, potentially, new pharmaceutical targets for AMD treatment.

Boston, Mass. — Patients with any stage of age-related macular degeneration (AMD) carry signs of the disease in their blood that may be found through special laboratory tests, according to a new study led by AMD researchers based at Massachusetts Eye and Ear. The study, published online today in Ophthalmology, describes a new technique known as “metabolomics,” which can identify blood profiles associated with AMD — the leading cause of adult blindness in developed countries — and its level of severity. These potential lipid biomarkers in human blood plasma may lead to earlier diagnosis, better prognostic information and more precise treatment of patients with AMD, as well as potential new targets for AMD treatment.

“With metabolomics, we can identify blood profiles associated with AMD and its severity through laboratory testing,” said co-senior author Joan W. Miller, MD, Chief of Ophthalmology at Mass. Eye and Ear and Massachusetts General Hospital, and Chair of Ophthalmology and the David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School. “Because the signs and symptoms of early stage AMD are very subtle, with visual symptoms only becoming apparent at more advanced stages of the disease, identification of biomarkers in human blood plasma may allow us to better understand the early to intermediate stages of AMD so we may intervene sooner, and ultimately provide better care.”  

AMD is the leading cause of blindness in people over 50 in developed countries, and its prevalence is expected to increase along with the global aging of the population. While AMD has recognized genetic and lifestyle risk factors, including diet and smoking status, the field currently lacks reliable measures to identify patients who may be at risk of developing AMD, including those who may progress to the advanced, blinding forms of the disease.

“The study utilized a technique known as metabolomics, or the study of the tiny particles called metabolites, in our body that reflect our genes and environment,” explained first author Ines Lains, M.D., a research fellow at Mass. Eye and Ear. “The metabolome — the set of metabolites present in an individual — is thought to closely represent the true functional state of complex diseases. This is why we used it to test 90 blood samples obtained from study participants with all stages of AMD (30 with early-stage disease, 30 with intermediate-stage and 30 with late-stage) and 30 samples from patients without AMD.” The metabolomics data analysis was performed in collaboration with Dr. Lasky-Su and colleagues at the Channing Division of Network Medicine of Brigham and Women’s Hospital.

Their approach revealed 87 metabolites, or small molecules in the blood, that were significantly different between subjects with AMD and those without. Furthermore, the team noted varying characteristics between the blood profiles of each stage of disease. This information has the potential to improve earlier diagnoses for AMD patients, and ultimately, may lead to more treatment options, as well as personalized treatment, for earlier stages of the disease.

Of the 87 molecules identified through metabolomics in the study to be associated with AMD, most belonged to the lipid pathway. In fact, six of the seven most significant metabolites identified in the study were lipids. Previous research has suggested that lipids may be involved in the development of AMD, although the exact role of lipids in the disease process remains unclear. The results from this study support this suggestion, as well as indicate that metabolomics profiling may provide novel insights into relationship between lipids and AMD.

“We believe this work will help launch the era of personalized medicine in treatment of AMD,” said co-senior author Deeba Husain, MD, a retina specialist at Mass. Eye and Ear and Associate Professor of Ophthalmology and co-director of the AMD Center of Excellence at Harvard Medical School. “Our work gives us a novel biomarker for early diagnosis, and it gives us clues to differentiate the progressers from non-progressors. This research also gives us insight into important role of lipids in AMD, which will provide novel targets for treatment in the early stage of disease, thus preserving vision in AMD."

In addition to Drs. Miller, Lains and Husain, authors on the Ophthalmology report include John B. Miller, MD, Demetrios G. Vavvas, MD, PhD, and Ivana K. Kim, MD, of Mass. Eye and Ear/Harvard Medical School, Rachel S. Kelly, PhD, and Jessica Lasky-Su, ScD, of the Channing Division of Network Medicine at Brigham and Women’s Hospital/Harvard Medical School, and Rufino Silva, MD, PhD, and Joaquim N. Murta, MD, PhD, of the University of Coimbra in Portugal. This research study was supported by the Miller Retina Research Fund, the Champalimaud Vision Award, Research to Prevent Blindness and the Portuguese Foundation for Science and Technology/Harvard Medical School Portugal Program.

About Massachusetts Eye and Ear 

Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. In the 2017–2018 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #2 in the nation ear, nose and throat care and #4 for eye care. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.

About Harvard Medical School Department of Ophthalmology

The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Schepens Eye Research Institute of Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.