About a decade ago, when Isobel Soukup went for a routine eye exam, her primary ophthalmologist discovered that the pressure inside her right eye, known as intraocular pressure (IOP; see “A Glaucoma Glossary”), was nearly twice as high as it should be. Soukup didn’t feel anything unusual, but she was exhibiting a classic early sign of glaucoma. She underwent a procedure called laser trabeculoplasty, which was effective in reducing IOP for about five years before the treatment needed to be repeated, not an unusual situation.
But one aspect of Soukup’s medical history is unusual. Some time after the second laser treatment, the IOP in both her eyes shot up, and Soukup was diagnosed with advanced glaucoma. She was scheduled by her ophthalmologist to receive a trabeculectomy, a well-established procedure that creates a drainage hole in the eye to reduce IOP, on her right eye. But due to complications with her conjunctiva, a thin layer of cells that covers the sclera (the “white” of the eye) and lines the eyelids, that surgery was aborted and she was swiftly referred to the Yale Eye Center (YEC).
During a lengthy surgery YEC doctors sutured a robust silicone device to the outside of Soukup’s right eye, which stabilized IOP. A few months later, her left eye also needed surgery, but this time YEC surgeons inserted an innovative shunt device still in clinical trials that does not require normal conjunctiva. Inserting the new device, known as the SOLX gold shunt, into Soukup’s left eye was far easier and quicker than using the silicone device, and Yale doctors and clinical researchers could now directly compare the effectiveness of the two treatments in the same patient.
Three months later, Soukup herself noticed a big difference. “It’s a wonderful thing they’ve created,” she says. “I can read, which I love, and TV viewing has cleared up considerably.” Her left eye is “working wonderfully,” she says, but the right “still has its moments when it leaks.”
Glaucoma is an irreversible, progressive disease in which elevated IOP damages the optic nerve. (However, for reasons that are not fully understood, 20 to 25 percent of patients suffer from “normal-tension glaucoma,” in which optic nerve damage has occurred despite normal IOP measures). If left untreated, glaucoma can lead to blindness. Of the 60 million people worldwide suffering from glaucoma (the latest figures are from 2010), the disease caused blindness in 12 million. Typically afflicting people in their 60s and older, it is known as “the silent thief of sight,” because it often goes undetected until 95 percent of the optic nerve is permanently destroyed. Medication, usually in the form of eye drops, is generally the first weapon used to treat IOP. In more complicated and aggressive cases, laser trabeculoplasty or trabeculectomy can be employed.
The School of Medicine has a long history in studying and treating diseases of the eye, having first incorporated ophthalmology as a distinct subject into the curriculum in 1876, but it would be nearly a century before the discipline was represented by a freestanding department. In 1961, the Connecticut Lions donated $18,000 to recruit Marvin L. Sears, M.D., from Johns Hopkins University to Yale to launch the Section of Ophthalmology in the Department of Surgery. The section grew rapidly, and in 1971 it was made a full-fledged department, the Department of Ophthalmology and Visual Sciences, with Sears—a glaucoma expert—as its inaugural chair.
Throughout the department’s history, a deep understanding of glaucoma has remained a calling card for Yale ophthalmologists. In 1978, the Food and Drug Administration approved the drug timolol, developed by Sears, for glaucoma—the first effective new treatment for the disease since the early 1900s—and the drug is still used today. Sears’ successor as chair, M. Bruce Shields, M.D., now professor emeritus of ophthalmology and visual sciences, also made significant advances in the diagnosis and treatment of the disease during his 15-year career at Yale.
Current chair James C. Tsai, M.D., M.B.A., the Robert R. Young Professor of Ophthalmology and Visual Sciences, is also an internationally recognized glaucoma clinician and researcher. To further enhance the department’s expertise in glaucoma, he recruited Nils Loewen, M.D., Ph.D., in 2009, and Tomas M. Grippo, M.D., in 2011. Both are leading physician–scientists who use state-of-the-art surgical techniques to treat glaucoma and also conduct research on the disorder’s causes and mechanisms.
“In my opinion, the glaucoma subspecialty can be viewed as the internal medicine of ophthalmology, because we get to know our patients for years or possibly decades,” says Tsai. “But if the therapeutic medications available are not effective, we can also perform laser or surgical procedures to help those patients retain their vision.”
In a healthy eye, a clear liquid, the aqueous humor, passes through the pupil and drains through a membrane called the trabecular meshwork, which filters the fluid and allows it to exit the eye and join the general circulation. In glaucoma, this membrane is blocked, much like a clogged sink, leading to increased IOP and possible optic nerve damage. “At its most basic level, glaucoma is a plumbing problem,” says Loewen, assistant professor of ophthalmology and visual sciences and director of the YEC’s Glaucoma Section. “You’ve got to improve the flow.”
But current surgical therapies are far from ideal, says Loewen. In trabeculectomy, for example, surgeons create a small hole in the eye underneath the eyelid to drain fluid, but in many cases scar tissue builds up and causes failure.
Patients with early to moderate glaucoma have recently been treated at the YEC with a newer procedure called a trabectome. This operation, which removes damaged portions of the trabecular meshwork, takes just a few minutes to perform, and the after-care only involves the use of drops for one or two months. “It requires much less maintenance, and the risks of severe complications are much less over the short term and the long term,” Loewen says. “It’s not going to replace the trabeculectomy—still the gold standard—but it’s another tool that we have if we identify the right patient.”
Loewen adds that “one of the bad things about classical trabeculectomy is that up to 50 percent of procedures fail after five years, while permanently increasing the risk for a devastating eye infection.”
Loewen hopes that the SOLX gold shunt received by Isobel Soukup received will provide an alternative to trabeculectomy for a much wider range of patients to avoid these complications.
About the size of a flattened grain of rice, the SOLX device is made of highly purified gold, an inert material that can remain entirely on the inside of the eye without increasing the risk of infection. The tiny plate, which is implanted through a single micro-incision, contains tubular channels that create a new drainage pathway to reduce IOP. The shunt can be inserted in about 20 minutes, and the patient’s vision returns to normal after only a couple of days. The device is undetectable by the patient and is intended to last indefinitely.
“Glaucoma is a devastating disease that causes disability and deprives us of our primary sense. Yet as we live longer, it’s only going to become more and more common,” says Loewen. “To have these new technology-driven micro-surgeries available to us is very gratifying.”
Besides surgery, the YEC is dedicated to using new medical science from all fields, including stem cell and gene therapies, to advance the understanding and treatment of glaucoma. Loewen conducts basic research to understand why IOP increases. He is currently working on a gene therapy designed to improve outflow by replacing the tissue that regulates flow, the trabecular meshwork.
Grippo has also a special interest in optic disc drusen, calcified deposits in the back of the eye that are associated with optic nerve degeneration. Optic disc drusen are a relatively frequent condition—studies have reported evidence of optic disc drusen in up to 2.4 percent of eyes—sometimes seen in patients who also present risk factors for glaucoma. “It’s very difficult to make a diagnosis of glaucoma when someone has optic disc drusen, mainly because the drusen obscure the normal anatomy of the optic nerve head, making optic nerve changes due to glaucoma very difficult to detect. Adding to this difficulty is the fact that both conditions may cause similar visual field loss.”
At present there is also no proven treatment for optic head drusen. Grippo hopes to launch long-term prospective studies at Yale to better understand the relationship between drusen and glaucoma and to seek better therapies.
Tsai believes that people who develop glaucoma may have unusually sensitive optic nerves that are easily damaged by fluctuations in IOP. Based upon this idea, Tsai has undertaken extensive basic and translational research, investigating neuroprotective agents in animal models of glaucoma, developing novel techniques for vision testing, and evaluating the surgical outcomes of glaucoma tube-shunt implants.
He has collaborated with colleague Steven M. Strittmatter, M.D., Ph.D., the Vincent Coates Professor of Neurology and professor of neurobiology, to study the role of a protein called NOGO that blocks nerve regeneration. By inactivating NOGO, it may be possible in the future to regenerate optic nerves that have already been damaged by glaucoma, Tsai says.
Tsai believes that advances in both biomedical engineering and neuroscience are the keys to future innovations in glaucoma research and treatment. In 10 or 20 years, he says, he hopes a new three-part paradigm for glaucoma treatment will have emerged, including therapies that rebuild the trabecular meshwork, protect the optic nerve from the effects of fluctuating IOP, and regenerate those optic nerve fibers that have been damaged by the disease. “This is indeed an exciting time to be engaged in glaucoma research and treatment,” he says.