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January 19, 2017

Research Notes

New retinal imaging technique developed


A new imaging technique developed by a School of Medicine researcher and colleagues could significantly advance how eye health and disease are assessed, according to the results of a study published in the Proceedings of the National Academy of Sciences. The method is the first to make out individual cells at the back of the eye that are implicated in vision loss in diseases like glaucoma, according to Ethan A. Rossi, ophthalmology faculty member. His research team hopes the new technique will prevent vision loss by enabling earlier diagnosis and treatment of these diseases.

Rossi developed the new method to non-invasively image the human retina, a layer of cells at the back of the eye that are essential for vision. The study was conducted by Rossi at the University of Rochester prior to his appointment at Pitt and led by Rochester colleagues.

Using the technique, the researchers were able to distinguish individual retinal ganglion cells (RGCs), which bear most of the responsibility of relaying visual information to the brain.

There has been a longstanding interest in imaging RGCs because their death creates vision loss with glaucoma, the second leading cause of acquired blindness worldwide. Despite great efforts, no one has successfully captured images of individual human RGCs, in part because they are nearly transparent.

Said Rossi: “This technique offers the opportunity to evaluate many retinal features that have previously remained inaccessible to imaging in the living eye. Not only RGCs, but potentially other nearly transparent cell classes as well.”

Instead of imaging RGCs directly, glaucoma currently is diagnosed by assessing the thickness of the nerve fibers projecting from the RGCs to the brain. However, by the time a change is typically detected in the retinal nerve fiber thickness, a patient may have lost tens of thousands of RGCs or more.

The new approach eventually may allow scientists to detect the loss of single ganglion cells, the researchers posit. The sooner such a loss is caught, the better the chances of halting disease and preventing vision loss.

The researchers were able to see RGCs by modifying an existing technology — confocal adaptive optics scanning light ophthalmoscopy (AOSLO). They collected multiple images, varying the size and location of the detector they used to gather light scattered out of the retina for each image, and then combined those images. The technique, called multi-offset detection, was performed in animals as well as volunteers with normal vision and patients with age-related macular degeneration.

Not only did this technique allow the group to visualize individual RGCs, but structures within the cells, like nuclei, also could be distinguished in animals. If that level of resolution can be achieved in humans, Rossi hopes to be able to assess glaucoma before the retinal nerve fiber thins — and even before any RGCs die — by detecting size and structure changes in RGC cell bodies.

While RGCs were the main focus of Rossi’s investigations, they are just one type of cell that can be imaged using this new technique. In age-related macular degeneration, cone photoreceptors that detect color and are important for central vision are the first to die. AOSLO has been used to image cones before, but these cells were difficult to see in areas near Drusen, fatty deposits that are the most common early sign of the disease. Using their multi-offset technique in age-related macular degeneration patients, Rossi was able to assess the health of cones near Drusen and in areas where the retina had been damaged.

Rossi and his colleagues warn that their study included a small number of volunteers and an even smaller number of age-related macular degeneration patients. More studies will be needed to improve the robustness of the technique before it can be widely used in the clinic. Rossi now is setting up his own laboratory and plans to continue working with the Rochester group in studying this technique and its ability to detect changes in retinal cells over the course of retinal diseases.

The study included other co-authors from Rochester and from Canon Inc.

It was funded by the National Institutes of Health (NIH), Canon, Edward N. & Della L. Thome Memorial Foundation and the University of Rochester Department of Ophthalmology via Research to Prevent Blindness

CMI spurs new biomedical device research

The Center for Medical Innovation (CMI) has awarded grants totaling $77,500 to four research groups through its 2016 round-two pilot funding program for early stage medical technology research and development. The latest funding proposals include a new technology for treatment of diabetes, a medical device for treating patients requiring emergent intubation, a new method for bone regeneration and a novel approach for implementing vascular bypass grafts.

CMI, in the Swanson School of Engineering, supports applied technology projects in the early stages of development with kick-start funding toward the goal of transitioning the research to clinical adoption. CMI leadership evaluates proposals based on scientific merit, technical and clinical relevance, potential health care impact and significance, experience of the investigators and potential for obtaining further financial investment to translate the particular solution to health care.

The awards went to the following projects:

• Intrapancreatic Lipid Nanoparticles to Treat Diabetes — to further develop and test the use of lipid nanoparticle technology for the induction of α-to-β-cell transdifferentiation to treat diabetes; George Gittes, faculty member in the Department of Surgery, School of Medicine; and Kathryn Whitehead, faculty member in the Department of Chemical Engineering, Carnegie Mellon University and McGowan Institute for Regenerative Medicine.

• The Esophocclude — a medical device for temporary occlusion of the esophagus in patients requiring emergent intubation; Philip Carullo, resident, Department of Anesthesiology, UPMC; and Youngjae Chun, faculty member in the Department of Industrial Engineering, Swanson school.

This is a continuation award for further refinement of the Esophocclude medical device, using human cadaver testing to simulate emergency intubation.

• RegenMatrix — collagen-mimetic bioactive hydrogels for bone regeneration; Shilpa Sant, faculty member in the Department of Pharmaceutical Sciences, School of Pharmacy; Akhil Patel, graduate student, pharmaceutical sciences; Yadong Wang, faculty member in the Department of Bioengineering, Swanson school; Sachin Velankar, faculty member in the Department of Chemical Engineering, Swanson school; and Charles Sfeir, faculty member in the Department of Oral Biology, School of Dental Medicine.

This is a continuation award for fully automating the hydrogel fabrication process, for animal studies and for fine-tuning related innovations.

• TopoGraft 2.0 — anti-platelet surfaces for bypass grafts and artificial hearts using topographic surface actuation; Sachin Velankar, faculty member in the Department of Chemical Engineering, Swanson school; Luka Pocivavsak and Edith Tzeng, faculty members in the Department of Surgery, School of Medicine; and Robert Kormos, faculty member in the Department of Cardiothoracic Surgery, School of Medicine.

This is a continuation award for in vivo validating of results and developing a new approach for topographic actuation of the inner lumen of synthetic bypass grafts.

Pitt, Bayer form research alliance

Pitt and Bayer have established a master collaboration agreement to advance research for heart, lung and blood disease indications. This broad collaboration spans from early research studies to drug development and big data analysis including real-world evidence studies. In addition to the research partnership, Bayer will be supporting an independent investigator-initiated clinical trial in sickle cell disease.

Said Mark Gladwin, the Jack D. Myers Professor and Chair of the Department of Medicine in the School of Medicine and director of the Pittsburgh Heart, Lung and Blood Vascular Medicine Institute: “Working with Bayer under this master agreement will allow us to further explore drug discovery research to better understand and meet patient needs.”

Improved access to care for veterans reported

Hypothetical Veteran Health Benefits Application

A recent study conducted by the Katz Graduate School of Business and the School of Pharmacy’s Program Evaluation and Research Unit (PERU), in conjunction with the Department of Veteran Affairs (VA), found that a new program to improve veterans’ access to care initiated over the past year has been effective.

MyVA Access, implemented in 2015, established sustainable solutions within VA facilities to improve veterans’ access to care.

Said Janice L. Pringle, pharmacy faculty member and co-principal investigator: “The VA has done a remarkable job of improving veteran care access across the system, especially for urgent care, in a relatively short period of time.”

The project evaluated the outcomes associated with the first year of the VA’s MyVA Access program as compared to those of the prior year. According to Jerrold H. May, Katz faculty member and co-principal investigator, two fundamental questions were examined: Has veterans’ access to urgent care improved as intended, and is the strategy of prioritizing urgent care appointments the better course of action? The study determined that the answer to both questions was a definite yes.

The study collected data from 140 VA health facilities across the country. Drawing on the responses to surveys that patients completed after receiving medical care and on information from VA operational data, a comparison of access-to-care measures was studied for roughly a one-year period.

Said May: “According to the data, access-related patient satisfaction improved significantly and complaints decreased significantly. Additionally, the wait time for urgent care-related consultations was improved at 74 percent of all VA facilities.”

The study determined the following successes in the MyVA Access program:
• The percentage of “always” and “usually” responses to a survey question related to a veteran’s ability to obtain an urgent appointment as soon as needed improved significantly.

• Veteran-perceived access improved overall.

• New patient wait times for appointments improved significantly in both mental health and specialty care clinics.

• The number of veterans per thousand who filed access-related complaints improved significantly in the period following the MyVA Access initiative.

• Improvements in access measures were generally consistent across facilities with differing baseline performance level designations.

Researchers made several recommendations for how the VA can better institutionalize the MyVA Access program, including engaging staff in communication programs; diffusing strong leadership principles throughout all levels of facility leadership; developing a simple performance measurement system; developing highly specific implementation plans; using effective methods for hiring staff; and implementing training programs that provide just-in-time knowledge and skills to staff.

—Compiled by Marty Levine

The University Times Research Notes column reports on funding awarded to Pitt researchers and on findings arising from University research. We welcome submissions from all areas of the University. Submit information via email to:, by fax to 412-624-4579 or by campus mail to 308 Bellefield Hall. For submission guidelines, visit

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