Researchers receive $3.7 million grant to diagnose and treat concussion-related eye disorder

Nearly half of adolescents and young adults with lingering symptoms of concussion suffer from an eye coordination disorder that causes blurred and double vision, headaches and difficulties concentrating. There is no proven method for treating the condition when it occurs after a head injury.

"The disorder makes it hard to read books, work on a computer or even use a smartphone, and the impact on cognition and learning can be severe. It also delays the return to sports, work and driving for young people," said Tara Alvarez, a professor of biomedical engineering at NJIT and an expert on convergence insufficiency (CI), a condition in which the muscles that control eye movements don't coordinate to focus on near objects.

Backed by a $3.7 million grant from the National Eye Institute of the National Institutes of Health, Alvarez is leading a multi-institutional team of engineers, optometrists, vision researchers, sports medicine physicians, balance experts and biostatisticians seeking to establish guidelines that will help clinicians diagnose and treat concussion-related CI. The funding follows a $2 million NIH grant that enabled Alvarez and her longtime clinical partner, Mitchell Scheiman, O.D., Ph.D., the dean of research at Salus University, to first investigate CI in people without head injuries.

"We want to come up with best practices to optimize therapy for individual patients, as well as the means to verify the results," Alvarez said, noting, "Physicians, for example, have a difficult time clearing people to return to sports or driving – they base their decisions on their experience in identifying symptoms. What they lack are quantitative measures to determine more precisely when it's safe."

The team is enrolling a demographically diverse group of 100 participants between the ages of 15 and 25 with persistent symptoms of CI one-to-three months post-trauma in clinical trials at the Children's Hospital of Philadelphia (CHOP) and Robert Wood Johnson's Somerset Pediatric Group in New Jersey. The source of their concussions varies, from falls, to car accidents, to sports injuries.

Arlene Goodman, a pediatrician at Somerset Pediatric Group and the former director of the concussion program at Saint Peter's University Hospital, noted that more than half of her patients have convergence insufficiency. They are currently referred to physical therapy, and if they don't respond, they follow up with vision therapy.

"Eye issues are the biggest issue in the majority of patients who have persistent symptoms post- concussion, especially during the school year," Goodman said, adding, "but it depends on the patient what is the most challenging issue: cognitive, psychological, autonomic dysfunction vestibular or ocular."

While testing their vision, assessing their ability to perform daily tasks such as reading, and collecting eye movement data to determine how quickly and accurately they can track a moving target on a computer screen, the group will also examine links to the brain. Through fMRI imaging, they will measure changes in blood oxygen levels in different regions of the brain while it is at rest and while people are moving their eyes, for example, as a way to determine how much energy is produced in these different modes and where it is directed.

Following a course of therapy sessions, they will repeat the tests to determine whether the patients' eye function has improved and how that is correlated with changes in the brain. In addition to levels of blood oxygen, Alvarez also measures how consistently neurons in the eye-functioning regions fire, whether cells near those neurons get recruited to help with tasks and whether connections between neurons improve so that signals flow faster and more effectively.

"The novelty of my work is to show how eye therapy works, including through changes we see in the brain undergoing neurorehabilitation," Alvarez said, adding "In these new tests, we will compare concussion patients with healthy people, as well as with those with non-concussion related CI, and look for significant differences between those groups to understand how a concussion impacts visual and oculomotor (eye movements to acquire visual information) performance."

She notes that some clinicians commonly view concussion-related CI as a different etiology because those patients often have concurrent vestibular dysfunction – they get dizzy – whereas typically occurring CI patients do not. "This may imply differences within the cerebellum between these two patient groups," she said.

"As someone who treats concussion patients, I am very optimistic that this study will provide the first evidence on how vision therapy changes the brain and results in clinical improvement in visual function in those who suffer from CI after concussion," said Christina Master, M.D., a pediatrician and pediatric sports medicine doctor at CHOP and principal investigator of the Center for Brain Injury and Repair at the University of Pennsylvania. "This would provide a sound basis upon which to develop standardized treatment protocols for concussion-related CI which would improve the quality of life for millions of patients suffering from this disorder."

Alvarez and Scheiman were the first researchers to describe how CI-related vision therapy changed brain mechanisms, reducing symptoms.

"We have completed multiple randomized clinical trials to compare various treatments for CI ranging from simple home-based procedures to more sophisticated office-based therapy administered by trained therapists. These studies demonstrate that home-based therapies alone have limited effectiveness and office-based vision therapy is the most effective treatment for patients with CI and no history of head injury," said Scheiman, who has studied CI for 30 years. "Our objective in this new study is to determine if a similar therapy protocol is also effective when CI occurs after concussion."

In their initial study, the partners focused on the frontal eye fields that control eyes movements and the oculomotor vermis, the central part of the cerebellum between the two hemispheres. In these new experiments, armed with enhanced imaging technology, the team will take a closer look at the entire brain, including the brain stem, which is susceptible to whiplash.

"Once we understand how vision therapy changes the concussed brain to improve visual function and its ability to restore patients to normal activities, we expect to develop personalized therapeutics," Alvarez said. Four years ago, Alvarez, Scheiman and two of her former graduate students, Chang Yaramothu and John Vito d'Antonio-Bertagnolli, formed OculoMotor Technologies, Inc., a medical device startup company that creates a range of virtual reality gaming exercises to diagnose and correct the motor disorder.

Physicians will receive a composite score of clinical and eye movement measures to assist in decisions for return to sport, school and other activities. This composite score will be based upon knowledge from the imaging conducted within this study.

Once they have gathered and published data, they plan to embark on a larger, randomized clinical trial with 500 patients in major children's hospitals across the country that specialize in concussions.