2008/2009 Warren Alpert Foundation Prize recipient Lloyd M. Aiello, MD

Lloyd M. Aiello, MD remembers a period in the 1960s when 50 percent of his patients went blind every year. Mostly young adults, they suffered from a complication of diabetes in which weak, leaky blood vessels proliferate in the retina, leading to hemorrhage and vision loss.

Today the vast majority of patients with this disease--called diabetic retinopathy--retain their vision, thanks to a treatment Aiello, an ophthalmologist, pioneered with his father-in-law--the late William P. Beetham--in 1967. Aiello will receive the prestigious Warren Alpert Foundation Prize on September 29 during a ceremony at Harvard Medical School (HMS) for improving the lives of patients with diabetes. As an Alpert Prize recipient, Aiello joins an elite group of physician-scientists and researchers, seven of whom have also won the Nobel Prize.

"Lloyd M. Aiello's contribution to the prevention of blindness in diabetic patients is huge," says George King, HMS professor of medicine and research director at Joslin Diabetes Center. "Before the laser treatment, 95 percent of diabetic patients would go blind if they lived long enough. Blindness in the diabetic patient is now only 5 percent."

Four decades later, ophthalmologists still use Aiello's treatment to save patients' sight.

"I firmly believe that he saved me," adds Winslow Sawyer, a patient of Dr. Aiello's who was diagnosed with type 1 diabetes in 1950 and had his first laser treatment in 1967. "He's the reason that I still see today after being diabetic for so long."

"It's been a remarkable 40 years," says Aiello, an HMS clinical professor of ophthalmology at Joslin Diabetes Center's Beetham Eye Institute.

Prior to the discovery of insulin in 1921, diabetic patients did not live long enough to develop complications in their eyes. By the 1950s, however, proliferative diabetic retinopathy was the leading cause of blindness in the United States. The life expectancy of patients with symptoms was still abysmal. Few individuals survived more than 5 years after their blood vessels began to leak and multiply, and in many cases, seeing-eye dogs outlived their owners.

As endocrinologists worked to extend the life expectancy of diabetic patients, Aiello and Beetham resolved to keep them from going blind.

Retinopathy develops when blood flow slows in the retina, compromising vessel walls. As a result, blood leaks and pools in the tissue instead of reaching its destination. Deprived of blood flow and nutrients, other regions of the retina release factors that stimulate the growth of new vessels, which in turn are weak, leak and perpetuate the problem.

By studying thousands of retinas, Aiello and Beetham observed something curious: they noticed that patients with extensive retinal scarring from other diseases did not go blind as quickly as their peers. This unexpected finding provided the first major clue on how to stop this vicious cycle.

"We decided to mimic the scarring observed in these patients to halt the proliferation of blood vessels in other persons with diabetes without significantly compromising the visual field," says Aiello.

In 1967, the team took advantage of new laser technology to create scars in the retinas of young women and men without destroying the entire eye. Working in a small room at Joslin Diabetes Center that doubled as a broom closet, the researchers developed a way to focus a parallel beam of light on each patient's retina, creating several hundred lesions on tiny regions of tissue, one at a time. The patients remained awake for this laser surgery.

After presenting preliminary results at a major diabetes conference, Aiello helped organize the Diabetic Retinopathy Study, a multi-center clinical trial for the National Eye Institute, in the late 1960s and 1970s, to rigorously test his technique, known as scatter or panretinal photocoagulation. The success of the project spawned additional clinical trials, which allowed Aiello and others to refine the method and set a new standard for diabetes care.

"We've come an incredible distance, but now we need to work toward preserving vision with a pill so that we can retire the lasers," says Aiello. "My son, Lloyd P. Aiello, is tackling this project, and I think he has a good chance of succeeding in 10 to 20 years."

After relinquishing the development of next-generation treatments to his son, Aiello turned his attention to another big problem in diabetes--health care delivery.

The worldwide trend is from epidemic to pandemic, with diabetes projected to afflict 366 million individuals by 2030, according to the World Health Organization. As incidence of the disease rises across the globe, Aiello is working to ensure that patients everywhere have access to the latest diagnostic tools and treatments in the future. He collaborated with Beetham Eye Institute colleague Sven-Erik Bursell to start the Joslin Vision Network (JVN), which brings cutting-edge medicine to diabetic patients in remote regions via digital imaging.

Today JVN serves patients from more than 70 different Native American reservations as well as a hospital in Venezuela. Joslin doctors train health care providers from each site to take high-resolution images of retinas. The images are sent to Joslin or Joslin-certified reading centers, where experts analyze and interpret them before writing a report. Based on this report, health care providers at the remote sites dispense advice and treatment to their patients.

"Our only hope for handling the impending diabetes pandemic is telemedicine--remote site imaging and delivery of treatment to patients wherever they happen to live," says Aiello. "We're developing and automating this model."