New findings may stimulate the development of targeted therapies for proptosis in patients with acute thyroid eye disease
Boston, Mass. — Researchers from Mass. Eye and Ear - including Schepens Eye Research Institute - and Boston Children's Hospital have identified new underlying mechanisms of proptosis, or bulging of the eyes, in patients with acute thyroid eye disease. In a report published online in the journal Ophthalmology, the researchers describe vascular growth factors causing an abnormal proliferation of blood vessels, as well as the rare formation of lymphatic vessels, that may contribute to the dangerous swelling and inflammation that occurs in the orbits of these patients. The findings point to new potential targets for non-surgical therapies to decompress the eye in the acute phase of thyroid eye disease.
“We’ve found that there is a proliferation of blood vessels, and, to our surprise, in some of those acute cases, lymphatic vessels do form where there normally aren’t any,” said corresponding author Leo A. Kim, MD, PhD, a retina surgeon at Mass. Eye and Ear and an Assistant Professor of Ophthalmology at Harvard Medical School. “Our results suggest that it might be possible to treat the inflammation and swelling by stopping the blood vessels from forming and leaking fluid, or, alternatively, by finding a way to promote lymphatic vessel formation and enhance drainage of fluid. This study opens a path to exploring non-surgical treatments.”
A potentially sight-threatening condition, thyroid eye disease is associated with Graves’ disease, an autoimmune disorder causing excessive production of hormones by the thyroid gland. Approximately 10 to 20 percent of patients with Graves’ disease experience severe inflammation of the eyes and surrounding tissues that can cause disabling double vision or permanent vision loss. Current treatment strategies for these patients rely on managing the swelling through systemic steroids — and sometimes, through invasive surgical techniques to realign the eyes or decompress the orbits by breaking bones.
With the hope of finding markers that may enable more targeted therapy, the researchers studied samples obtained from 15 patients with thyroid eye disease undergoing orbital decompression. In samples from the acute, inflammatory stage of the disease, they found that both rare lymphatic vessels and robust blood vessels had formed.
While more studies are needed, the proliferation of leaky blood vessels not only offers an underlying mechanism for the swelling, but also offers the potential to be controlled with local administration of angiogenesis inhibitors (such as anti-VEGF). Moreover, by determining the mechanisms underlying lymphatic vessel formation in the acute stage of the disease, the creation of functional lymphatic vessels may be utilized as a therapeutic option to better drain fluid from the orbit.
“This exciting study gives us some new insights into how we might get to the root cause of this devastating disease and better manage it through less invasive treatments that will improve quality of care for our patients,” said Dr. Kim.
Leo A. Kim, M.D., Ph.D., Massachusetts Eye and Ear/Harvard Medical School, is corresponding author of the Ophthalmology report. Additional co-authors are Lindsay L. Wong, BA, Nahyoung Grace Lee, MD, Dhanesh Amarnani, MS, Catherine J. Choi, MD, MS, Suzanne K. Freitag, MD, of Massachusetts Eye and Ear; Patricia A. D’Amore, PhD, MBA, of Schepens Eye Research Institute of Massachusetts Eye and Ear/Harvard Medical School; and Diane R. Bielenberg, PhD, of Boston Children’s Hospital/Harvard Medical School.
The research study was supported by the American Thyroid Association, the Massachusetts Lions Eye Research Foundation, the Vascular Biology Program at Boston Children’s Hospital and National Eye Institute grants EY005318, P30EY003790 and EY16335.
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 2016–2017 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #1 in the nation for ear, nose and throat care and #1 in New England 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, 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.
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