Success in Sight with Diabetes
Joslin’s eye research team shows progress against the most feared complication of diabetes
Beginning in the 1960s, the laser photocoagulation technique pioneered by William P. Beetham, M.D., and Lloyd M. Aiello, M.D., became the worldwide standard of care for reducing vision loss from diabetes. Joslin’s eye research team, which still carries the leadership torch, today is energized by important new results.
Joslin scientists are identifying factors that trigger molecular changes in the eye and finding promising ways to halt these processes. Researchers also are seeking biological factors that aid in early detection or actively protect against eye disease. Additionally, in global telemedicine, Joslin is developing online tools to offer diabetes patients the highest standards of care wherever they live.
New drug for diabetic macular edema
In diabetic retinopathy (damage to the retina in the back of the eye), loss of vision occurs in two primary ways.
With proliferative, or advanced, diabetic retinopathy—affecting more than 700,000 U.S. patients—blood vessels grow in the eye where they don’t belong. Laser treatment generally works well to treat this disease.
Diabetic macular edema, which afflicts more than 500,000 patients, results from leaking of blood vessels that causes swelling in the macula, the area of the retina responsible for our sharpest vision. Left untreated, about a quarter of people with diabetes eventually suffer vision loss from macular edema.
“Laser treatment has been the gold standard intervention for diabetic macular edema over the past 25 years, but now we have an even better therapy that can be used alone or in conjunction with laser—injecting a drug called ranibizumab,” says Lloyd Paul Aiello, M.D., Ph.D., director of Joslin’s Beetham Eye Institute and head of Joslin’s eye research initiatives. The drug targets a key player in blood vessel growth—a protein called vascular endothelial growth factor (VEGF).
Dr. Lloyd Paul Aiello led the basic research that took the first steps toward this treatment, which was endorsed by a landmark clinical study by the Diabetic Retinopathy Clinical Research Network in 2010. In the 1990s, Dr. Aiello and George L. King, M.D., Joslin’s Chief Scientific Officer, observed heightened activity of VEGF in patients with diabetic eye disease and undertook basic research studies to understand the process.
The 2010 clinical study shows anti-VEGF drugs can dramatically reduce vision loss and improve the chance of vision gain, actually stopping leakage in half the patients. Additional clinical trials are being launched to see if similar but less costly anti-VEGF drugs will provide a comparable effect.
Protecting against inflammation
VEGF is only part of the equation, perhaps accounting for about half of diabetic macular edema cases. To illuminate the other cases, Edward P. Feener, Ph.D., is studying the breakdown of the retina’s protective barrier and the subsequent march of inflammatory proteins into the retina.
Using proteomics, the large-scale study of protein structure and function, Dr. Feener identified a troublemaking non-VEGF pathway triggered by a protein called plasma kallikrein. In addition to its role in diabetic macular edema, this protein is part of a potent inflammatory system involved in high blood pressure, kidney disease and stroke.
“By identifying promising new drugs that target plasma kallikrein and other proteins involved, we hope to find ways to reduce retinal swelling and possibly benefit other inflammatory conditions,” says Dr. Feener.
Prediction and prevention
Remarkably, some Joslin 50-Year Medalists, who have survived with diabetes for more than five decades, still have little or no diabetic retinopathy, notes Jennifer K. Sun, M.D., M.P.H. A large majority of these patients maintain perfect or excellent vision despite having lived with diabetes for 50 years or more.
“We are investigating factors that may have been involved in their long survival and protected them from diabetic eye complications and vision loss over the long term,” says Dr. Sun. “By identifying key molecules or pathways that protect these unique patients and understanding how they prevent diabetic eye disease, we hope to create novel treatments that can benefit all patients with diabetes, including those who are naturally more susceptible to eye complications.”
She and her colleagues also are seeking ways to predict which patients with diabetes will develop retinopathy by correlating the presence of eye complications with biological markers (substances that can help to indicate a condition), measurements of retinal blood flow and retinal thickness, and ultra–high-resolution images of the various layers of the retina.
Sharing vision with the world
With their state-of-the-art eye care, most Joslin patients retain 20/20 or better vision. How can this success be replicated worldwide—especially 20 years from now, when more than 400 million people will have diabetes?
The Joslin Vision Network, which was formally established in 1998 by Dr. Lloyd M. Aiello and Sven E. Bursell, Ph.D., may hold the answer. With specialized cameras, software and digital data securely transmitted online, the network allows patients to be evaluated from any location worldwide.
Images and other key patient data, including blood pressure and blood glucose measurements, can be transmitted to Joslin in Boston, where an expert ophthalmology team evaluates the images and provides treatment guidance, explains Paolo S. Silva, M.D., assistant chief of telemedicine.
On the horizon, Joslin is seeking funds to expand the network and bring its level of diabetes eye care to patients worldwide. One notable goal is to create an automated portable helmet that patients wear for 15 minutes, capturing and transmitting eye and other medical data to an ophthalmology team in another part of the world who guide their care, says Dr. Lloyd M. Aiello, whose entrepreneurial spirit continues to catapult Joslin’s eye research to new heights.
“We have made great strides in preserving vision and preventing blindness because we’re willing to take risks,” he says. “But to take risks and be successful, you must be dedicated and understand the disease and the needs of our patients. That’s Joslin’s legacy and model for the future.”
“Laser treatment has been the gold standard intervention for diabetic macular edema over the past 25 years, but now we have an even better therapy,” says Lloyd Paul Aiello, M.D., Ph.D.
Searching for drugs with potential to treat diabetic macular edema, Edward P. Feener, Ph.D., studies proteins involved in retinal inflammation.
Jennifer K. Sun, M.D., M.P.H, investigates why so many Joslin 50-Year Medalists maintain perfect or excellent vision despite living with diabetes for many years.
The Joslin Vision Network can transmit images and other data to Joslin, where an expert ophthalmology team provides treatment guidance, explains Paolo S. Silva, M.D.
Leveraging Joslin’s achievements in telemedicine can provide a desperately needed model for treating diabetic eye disease worldwide, says Dr. Lloyd M. Aiello.