RetınaWILMERRounds A newsletter from the Wilmer Eye Institute, Johns Hopkins Medicine DECEMBER 2017

Adrienne Scott, M.D. Seeing Sickle Cell Anew drienne Scott, M.D., chose to join the ranks blood disorder, sickle cell disease occurs when the normally spherical- of specialists because, she says, they are shaped red blood cells have a sickle known as “the Marines of the eyes. We’re the shape, which deprives body parts of oxygen. “Sickle cell patients can people they call in when an urgent problem have problems with every organ A system in the body, but the eyes are arises.” An assistant professor of in particularly vulnerable given all the Wilmer’s Retina Division, Scott also serves as the chief of (continued on page 3) the Wilmer satellite office in Bel Air. While she sees patients with years ago from complications of “I hear from people all manner of retinal diseases, she sickle cell disease who told her “we over and over, ‘You has a specific interest in sickle cell need to cure this,” Scott decided to can take any sense retinopathy, a condition caused dedicate herself to studying sickle of mine, but I cannot by sickle cell disease. Inspired by cell retinopathy. lose my eyesight.’” a patient who passed away a few The most commonly inherited

Artificial Intelligence Achieves Looking for Harnessing the Super INSIDE1 2 Accuracy in Diagnosing AMD 4 Common Ground 5 Power of VirusesRETINA ROUNDS Artificial Intelligence Achieves Accuracy in Diagnosing AMD

From the Desk of Neil Bressler, M.D., Chief of the Retina Division: ccording to a recently published article by Retina Division specialist Adrienne AScott, M.D., Americans regard losing eyesight as having the greatest impact on their daily lives. The physicians of Wilmer’s Retina Division, one of the largest university-based retina practices in the U.S., dedicate their time, energy and passion to combatting retinal diseases to preserve vision. The research by the clinician- scientists of the Retina Division spans investigations from the laboratory to the clinic and frequently leads to publication in the nation’s top medical journals. In addition, each year hundreds of patients seen by doctors in the Retina Division participate in rtificial intelligence has become a new clinical trials to help move the field player in health care and one that Neil forward. Retina Division physicians Bressler, M.D., Wilmer’s James P. Gills disseminate the knowledge gleaned Professor of Ophthalmology and chief of the from their research through courses A taught to thousands of other Retina Division, sees as an ally in the battle to save the ophthalmologists, both in Baltimore vision of people with age-related and around the world each year. And while the Retina Division has (AMD) and other retinal diseases. How? By diagnosing been very successful at obtaining the cases early enough that intervention can succeed. competitive research dollars from government and industry, these “There are eight million people who fundus images of the retina. Drusen sources continue to be at risk of have an earlier, often asymptomatic are debris accumulating behind the shrinking, making it even more stage of AMD that need careful retina, the light-sensitive tissue that important to continue to secure the monitoring, but we estimate only lines the inside back wall of the eye. very generous support provided by about four million of them know DCNNs fall under the umbrella donors. they have it,” says Bressler. He and of machine learning, a field that We share the successes and plans his lab have teamed with the Johns seeks to teach computers to teach for that support in this Retina Hopkins Applied Physics Lab to themselves new information using Rounds to keep you up-to-date on create Deep Convolutional Neural generic algorithms that can be research and treatments that could Networks (DCNNs), which are applied to a wide range of data sets. have a substantial impact on your computer programs, to recognize the What Bressler’s DCNN teaches itself daily lives! n hallmark of AMD—drusen—on is how to recognize drusen.

2 RETINA ROUNDS Artificial Intelligence Achieves Accuracy in Diagnosing AMD Sickle Cell continued from page 1 small vessels, especially within the retina,” says Scott. “There are eight million people who have With the arrival of new imaging an earlier, often asymptomatic stage of techniques—such as optical AMD … but we estimate only about four coherence tomography (OCT) million of them know they have it.” angiography—that can help visualize the retina in finer detail than ever before, Scott believes research into sickle cell retinopathy is poised for a breakthrough. “We’re using OCT angiography to visualize blood flow According program or teach itself,” says Bressler. at a very detailed level. And we to Bressler, Bressler’s lab recently published can not only visualize blood flow, the DCNN is the results of its efforts, which found but also in the case of sickle cell told what the that the DCNN accurately identified retinopathy, we can visualize lack of “ground truth AMD between 88.4 percent and blood flow in the retinal circulation,” is” by viewing 91.6 percent of the time, in JAMA says Scott. images fed to (Journal of the American Medical Traditionally, sickle cell it of fundus Association) Ophthalmology. Such retinopathy has been considered photographs accuracy is comparable with human a disease of the periphery of the of the retina— expert performance levels. retina—and damage to this area these images Once the DCNNs become as causes the most severe vision loss. Neil Bressler, M.D. are referred accurate as possible, then Bressler With OCT angiography, however, to as the sees an opportunity for pieces Scott has seen changes in the blood “training data set.” While viewing of optical equipment—perhaps flow around the macula—the part the training data set, the DCNN is attachments to smartphones or of the retina responsible for central told, ‘This fundus image has drusen, kiosks in drug stores—to be created vision. this one does not.’ After viewing that can capture the fundus images If Scott finds a correlation thousands of sets of images, the in a cost-effective way. between lack of blood flow to the program learns to sort the images “We don’t have the resources macula, which OCT angiography into the two categories with or the personnel to get to can visualize quite clearly, and lack increased accuracy. everybody and screen of blood flow to the periphery of Once the DCNN is for asymptomatic, the retina, this could help doctors trained, researchers common retinal treat patients more effectively. OCT feed it images diseases that need angiography could serve as a fast without telling it, monitoring or and noninvasive screening tool to ‘This fundus image treatment,” says predict which patients could be most shows drusen, this Bressler. “But if at risk for future vision loss and thus one does not.’ Because we can find very require closer monitoring. the program has seen inexpensive ways to That would be a welcome and sorted enough images have the images analyzed development for this clinician- in the training data set, it A healthy retina to indicate, ‘This person scientist whose focus on her patients accurately recognizes images of has a high likelihood to propels her work. “I hear from drusen it has not seen before. need monitoring for AMD, but that people over and over, ‘You can take “What makes this artificial person doesn’t,’ that has the potential any sense of mine, but I cannot lose intelligence is that you’re not to help an enormous number of my eyesight,’” Scott says. “It’s a very programming it and then it does people around the world.” n critical sense and it’s an honor to be its thing. You’re programming it to able to try to maintain that.” n

3 RETINA ROUNDS Looking for Common Ground

he human body is is essentially the endpoint of complex. The division many retinal diseases, including of medical practice into macular degeneration and diabetic Tsubspecialties, focusing retinopathy. My goal is to identify on the intricacies of a single organ new strategies to protect retinal or organ system, is one way health neurons.” care has evolved to handle this Mitochondrial dysfunction fact. This solution, however, has its plays a critical role in Parkinson’s limits. And as medical research has disease as well, which is where progressed, the pendulum has begun Dawson’s research comes into play. to swing the other way—toward “Dr. Dawson studies pathways emphasizing the similarities between of mitochondrial function in the organ systems and the connections dopamine-producing neurons in between specialties. the brain that, when perturbed, Such a shift makes sense to Mira Mira M. Sachdeva, M.D., Ph.D. contribute to neurodegeneration in M. Sachdeva, M.D., Ph.D., who Parkinson’s disease,” says Sachdeva. recently joined Wilmer’s Retina “I’m starting to look at whether Division. As a retina specialist, there are parallel pathways in the Sachdeva sees these connections “I’m interested in retina that contribute to retinal every day. “You’re literally looking how mitochondrial neurodegeneration in diabetes.” at part of the brain by looking into metabolism in the She thinks this line of inquiry the eye. The retina is an extension retina affects cell could complement the existing focus of the brain,” she explains. To that of research and survival and how end, she recently began a research treatment—which is on retinal blood abnormalities in this project under the mentorship of vessels. Abnormalities in the retinal a neurologist at Johns Hopkins, can lead to cell death blood vessels are the diagnostic Ted M. Dawson, M.D., Ph.D.—“a and loss of retinal hallmark of the disease, Sachdeva world expert in neurodegenerative tissue.” says. And current treatments for diseases, specifically Parkinson’s,” diabetic retinopathy, such as anti- says Sachdeva. vascular endothelial growth factor Why is a retina specialist (anti-VEGF), target those blood interested in Parkinson’s disease? The vessels. mitochondria. “But there’s more and more Frequently referred to as evidence coming out that even the “powerhouses” of the cell, before you see changes in blood mitochondria break down nutrients vessels in patients with diabetes, (fats, sugars, proteins) taken in you can see loss of retinal neurons. by the cell and combine these No one knows what causes this with oxygen to create energy-rich early retinal neurodegeneration in molecules. “I’m interested in how diabetes,” she says. “And if we could mitochondrial metabolism in the target another pathway and even retina affects cell survival and how another cell type, we might be able abnormalities in this can lead to to prevent vision loss further. It’s cell death and loss of retinal tissue,” exciting.” n says Sachdeva. “Even though the specific layer of the retina involved may differ, retinal neuronal death

RETINA ROUNDS 4 Harnessing the Super Power of Viruses

or the clinician-scientists drawbacks. For many at Wilmer, seeing patients patients, especially those has two benefits: making with macular degeneration, Fa difference in people’s the therapy is usually lives and creating a guide for lab effective for only four to research. “Because I treat patients six weeks at a time; thus, in the clinic, I know the really such patients must come pressing problems, the unmet needs in for shots frequently. that patients have,” says Peter Campochiaro is striving to Campochiaro, M.D., the George S. eliminate this burden. and Dolores Doré Eccles Professor of Rather than injecting Ophthalmology and Neuroscience. the anti-VEGF directly “That has helped me to focus my into the eye, his strategy laboratory work.” is to inject something that One of those needs is controlling will produce the anti- a protein called vascular endothelial VEGF within the cells of growth factor (VEGF), which plays the eye—a virus. a critical role in causing a number “Viruses are very good of retinal diseases, from neovascular at getting into cells,” age-related macular degeneration to says Campochiaro. “We diabetic . Since 2006, engineer the viruses so however, a doctor has been able to that we take out all of

meet this need with anti-VEGF Peter Campochiaro, M.D. their inside machinery injections, which contain antibodies but we use the outside and proteins that bind to VEGF, in called the capsid, which the vitreous of a patient’s eye. “These is able to penetrate cells. proteins act like a sponge and soak up the VEGF,” And we replace the bad viral genes with good genes that says Campochiaro. produce the therapeutic protein we now continually While the anti-VEGF treatments are very effective inject in the eye.” compared with previous options, they are not without The therapy, which involves a 30-minute procedure, is now in a phase I/II clinical trial to test for both safety and efficacy. “We have a lot of indications that this treatment will produce the protein at a Retina Division Faculty good level, for a very prolonged period of time,” says Neil M. Bressler, M.D., Chief, Retina Division Campochiaro—which could be life-changing for Susan B. Bressler, M.D. patients. “We could be able to reduce or eliminate Peter Anthony Campochiaro, M.D. injections in the majority of patients.” Daniel Finkelstein, M.D. Campochiaro has worked on this solution as it has Peter Louis Gehlbach, M.D., Ph.D. progressed from the lab to the clinical trial and has James Tahara Handa, M.D. enjoyed the discoveries along the way. “When you find Catherine Blume Meyerle, M.D. out something new that you can add to the body of Mira M. Sachdeva, M.D., Ph.D. scientific knowledge, it’s really exciting,” he says. “And Adrienne Williams Scott, M.D. then when you see how those new pieces of knowledge Mandeep Singh, M.D., Ph.D., M.B.B.S. can add up to something that can help patients, then it Akrit Singh Sodhi, M.D., Ph.D. really becomes rewarding.” n Sharon Denise Solomon, M.D. Adam Scott Wenick, M.D., Ph.D. Ingrid E. Zimmer-Galler, M.D.

RETINA ROUNDS 5 WILMER RetınaRounds NON-PROFIT ORG. U.S. POSTAGE PAID LUTHERVILLE, MD For information on how to support PERMIT NO. 171 the Wilmer Eye Institute, contact: Libby Bryce Bell Wilmer Development Office Email: [email protected] Phone: 410-955-2020 Editor, writer: Jessica Wilson Designer: Max Boam Retina Rounds is published once a year by the Wilmer Eye Institute. If you prefer not to receive communications from the Fund for Johns Hopkins Medicine, please contact 1-877-600-7783 or [email protected]. Include your name and address so that we may honor your request.

A New Frontier in Retinal Degeneration Research

ction. that is the new degeneration research checks built in for the watchword for those because the institute is patients involved.” who study, treat or suffer an academic medical Currently, clinical from retinal degenerative center with “the trials in stem cell A Mandeep conditions, according to right facilities, staff, therapy, gene therapy, Singh, M.D., Ph.D., M.B.B.S., expertise and number electronic microchips assistant professor of ophthalmology of patients” to qualify and chemical in Wilmer’s Retina Division. “In the as a site to participate compounds are in past, with such chronic degenerative in these studies. progress. “Name any conditions, the main role of the He also other organ—from physician was to support people acknowledges the the liver to the spinal Mandeep Singh, M.D., through the process of visual change. bravery of patients Ph.D., M.B.B.S cord—where so many But in recent years, it’s really become in this process. strategies are in clinical a field of positive action,” says Singh. “For the patient to take the act of trials,” says Singh. He implies that A giant hurdle was recently volunteering their body and their one cannot. cleared with the launch of numerous time and energy to be in a trial with “Because of great partnerships clinical trials now available to so many unknowns is an act of between laboratories, industry patients. “For these conditions to be tremendous courage and generosity,” and medical centers like ours, in in good, well-run human clinical says Singh. the next decade we will hopefully trials is a big threshold that we’ve Patients should be cautious when see the approval of a range of new crossed,” says Singh. “Finally, there’s seeking clinical trial opportunities, treatments for people with previously a glimmer of hope that some of the however, Singh warns. He incurable conditions,” says Singh. ideas that have been incubating in recommends consulting with a “And we are honored, privileged labs for years are actually finding specialist to evaluate whether an and excited to be a site for clinical their way into trials.” experimental drug or procedure is trial research in retinal degenerative Singh sees Wilmer as a key “offered in the context of a well-run diseases.” n player in this next phase of retinal clinical trial, and has strong safety

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6 RETINA ROUNDS