Retina Research: A Spirit of Collaboration

By Ava Kikut

Scheie Vision Summer 2017

Scheie’s retina researchers collaborate with other departments and institutions in cutting-edge studies, seeking to improve diagnostic methods and treatments for a variety of diseases.

Dr. Benjamin Kim, who joined Scheie’s retina and vitreous service five years ago, has been involved in an impressive number of research initiatives. “I was always very interested in retina because it’s such a remarkably dynamic field,” he said. Dr. Kim is currently leading two potentially groundbreaking projects: a study using retinal imaging to diagnose frontotemporal degeneration and a clinical trial to test a treatment for age-related macular degeneration (AMD).  

Retinal Imaging and Diagnosing Frontotemporal Degeneration

Dr. Kim has been collaborating with UPenn neurologists, Drs. Murray Grossman and David Irwin. “We’re looking at potential relationships between the eye and the brain in frontotemporal degeneration (FTD),” Dr. Kim explained. FTD is a neurodegenerative condition that can cause a progressive decline in behavior, speech, and/or motor difficulties.  

Dr. Kim is exploring the potential of retinal imaging to aid in identifying and categorizing FTD. His research involves the use of ocular coherence tomography (OCT) to investigate retinal changes in FTD patients. “We have been using software to perform detailed measurements of the different layers of the retina in the OCT images of patients with FTD and then comparing those to control patients,” said Dr. Kim. “The field needs highly reliable, and easy to test biomarkers, and OCT is a simple way to image a patient.  Finding a retinal abnormality on OCT would open the door to other ways in which the retina can be studied to learn about FTD.  This has been a stimulating collaboration as new knowledge often develops at the intersection of two fields.” 

One objective of the study is to find a biomarker for patients with FTD that can subcategorize them based on their underlying molecular pathology. Usually, the disease results from the abnormal accumulation of either the tau protein or the TDP-43 protein. It is often difficult to clinically determine which underlying protein problem is affecting a patient. The discovery of a biomarker for FTD subtypes, such as a retinal abnormality, would potentially allow patients to be diagnosed earlier and then enroll in clinical trials testing treatments targeting the appropriate protein.   

Another goal of the study is to investigate the potential of retinal imaging to more effectively differentiate between FTD and Alzheimer’s Disease. Memory loss in Alzheimer’s patients is often confused with the behavioral symptoms of FTD. Postmortem neuropathology testing has shown that up to 30% of patients thought to have FTD while alive turned out to have Alzheimer’s Disease. “It’s critical to develop biomarkers to help differentiate FTD from Alzheimer’s disease,” stated Dr. Kim.  
This study has enrolled over 40 FTD patients and enrollment is ongoing.  

Testing a Treatment for Geographic Atrophy 

Dr. Kim is also involved in the Geographic Atrophy Lipoic Acid (GALA) Study, along with Drs. Josh Dunaief, Maureen Maguire, and Alexander Brucker. This clinical trial is testing alpha lipoic acid as a treatment for geographic atrophy.  

Geographic atrophy is an advanced form of AMD that causes the outer retina to develop atrophic lesions, which manifest as blind spots in the patient’s central vision. Over time, atrophic lesions grow and these blind spots enlarge. “Many patients have difficulty seeing the faces of their grandchildren or reading because of these lesions,” explained Dr. Kim. Geographic atrophy causes approximately 20% of the legal blindness in the United States, and there is no existing treatment. “As a major cause of blindness, geographic atrophy is a focus of a tremendous amount of research right now…there is a race to find a treatment,” said Dr. Kim.  

While age-related eye disease study (AREDS) vitamins are used to reduce the progression to advanced stages of AMD, they have not proven effective as a treatment for geographic atrophy. Unlike the antioxidants in AREDS vitamins, alpha lipoic acid affects glutathione, an important enzyme for cellular oxidation control. Alpha lipoic acid also has the potential to remove excess iron, which may contribute to geographic atrophy. Dr. Kim believes the potent antioxidant and iron chelating functions of alpha lipoic acid could slow down the growth of geographic atrophy lesions.  

GALA will administer oral supplements of alpha lipoic acid to patients with geographic atrophy. After eighteen months, the outcomes of patients taking the study drug will be compared to patients taking a placebo.  

“The trial has been a collaborative effort based on data from Josh Dunaief’s lab,” explained Dr. Kim. “What’s especially exciting about this study is that it is very much a home grown multicenter clinical trial.” Of the principal investigators (PI) for the project’s four external sites, three are alumni of the Scheie Eye Institute. These PIs include: Paul Hahn (res ’10) at New Jersey Retina, Apurva Patel (res ‘11) at Retina Northwest, and Allan Hunter (fel ‘11) at Oregon Retina. The fourth PI is Karen Gehrs, Professor of Clinical Ophthalmology at the highly regarded University of Iowa Department of Ophthalmology. This study is funded by several foundations, including BrightFocus, Cures Within Reach, and the Pennsylvania Lions.  

Dr. Kim has enjoyed working with a range of physicians, departments, and organizations since coming to Scheie. “These are collaborative research efforts and I don’t think that you can easily get this level of collaboration at all institutions,” he said. “Something I found that distinguishes Scheie is the overall friendly and cooperative attitude of people, which is also true for the University of Pennsylvania and its medical school.”