virtual reality
A virtual reality orientation and mobility course.
By Alexandra Brodin

Scheie Vision Summer 2021


Investigators at the University of Pennsylvania (UPenn) Department of Ophthalmology have shown that virtual reality (VR) technology may offer an effective method of assessing functional vision in children and adults with inherited retinal diseases.


Functional vision refers to a patient’s use of vision to perceive his or her environment and has traditionally been assessed using a physical orientation and mobility (O&M) protocol. An O&M protocol evaluates the patient’s ability to comprehend his or her own position relative to the immediate environment and to navigate this space safely without aid.


Tomas Aleman, MD, Associate Professor of Ophthalmology, Jean Bennett, MD, PhD, F.M. Kirby Professor of Ophthalmology and Co-Director of the Center for Advanced Retinal and Ocular Therapeutics (CAROT), and collaborators, including Alex Miller at the UPenn Neurology Virtual Reality (VR) Laboratory, recently investigated a new type of O&M protocol. Their study, published in Clinical Ophthalmology, provides proof-of-concept data that using a VR O&M test is a safe and effective way to assess and quantify functional vision. The population for this study included both control subjects with normal vision and patients with RPE65-associated retinal disease, including patients who had been treated with gene therapy.


Physical versus VR Courses


Physical O&M courses were used in clinical trials of Luxturna, the first FDA-approved gene therapy for an inherited disease. Luxturna was developed by Dr. Jean Bennett, Albert Maguire, MD, Professor of Ophthalmology, and Katherine High, MD, Emeritus Professor of Pediatrics at the Perelman School of Medicine and President and Chief Scientific Officer at Spark Therapeutics, among other collaborators. This gene therapy treats RPE65-related Leber’s congenital amaurosis (LCA), a group of blinding childhood retinal diseases. In O&M courses used for the Luxturna trials, study participants followed arrows to reach a door that marked the end of the course under different levels of illuminance, avoiding obstacles along the way. Illuminance refers to the amount of light hitting an object or surface.


With VR mobility tests, study participants used goggles containing a head tracker, hand trackers held at waist level, and foot trackers to complete a virtual course similar to the one described above, including arrows to follow and obstacles to avoid. Prior to the official tests, participants were given time to practice and become familiar with the VR equipment. Investigators purposely kept the visual scenery simple to avoid complicating interpretation of results. Objects appearing in the VR course were achromatic and set against a dark background.


The virtual tests took place in two steps. The first step consisted of an orientation task, in which participants were evaluated on their ability to follow a path of red arrows. A luminance of the arrows was identified at which the participant was able to complete the course. Luminance, in contrast to illuminance, refers to the intensity of the light emitted from a surface. The layout of the course was changed between each attempt so participants could not memorize the path.


In the second step, participants were again instructed to follow the arrows, but obstacles such as boxes, spheres, and hanging signs were added to test the ability of the participants to use their vision to avoid collisions. Similar to the first step, the luminance of the objects was increased until patients could effectively avoid them without compromising speed and accuracy.


The investigators monitored each participant’s progress from a desktop computer. Successful course completion depended on speed and accuracy, which the VR software was able to record automatically during the tests.


Accuracy was based on whether the participant stepped on each arrow as instructed. Errors included placing both feet outside the path, going off course, and colliding with obstacles. The investigators used the multi-luminance mobility test (MLMT) grading system to assign penalties for these errors. Dr. Bennett collaborated with vision scientists from the Children’s Hospital of Philadelphia to develop the MLMT grading system, which was then validated under sponsorship of Spark Therapeutics and published in 2018.


Value of VR


The use of VR courses is not only safe and effective, but may also overcome several of the challenges associated with physical O&M courses. Among these challenges is limited capacity for evaluating a wide range of vision loss severity. With VR courses, investigators may be able to assess a broader spectrum of disease severity because of their ability to limit complexity of visual stimuli and precisely adjust visual cues within the simulation.


“In future studies we can tailor the test to each individual retinal disease in order to both diagnose the condition and to monitor effects of treatment,” said Dr. Aleman. “For example, for Stargardt disease, an inherited macular degeneration, we can add chromatic stimuli and tasks that require a higher level of visual discrimination than required in the current test.”


Physical O&M courses also require investigators to spend significant time and resources to ensure that the space is prepared with proper course set-up and homogenous lighting, among other requirements. Adjusting the physical layout between tests to inhibit memorization was also time-consuming. VR O&M courses offer many features that serve to overcome many of these challenges, including the automatized detection and recording of a participant’s test performance, the lack of need for a specialized physical space, and the capacity for quick randomization of courses as well as modification of objects. In addition, the use of virtual obstacles eliminates the patient’s risk of tripping and falling on real objects in the course.


“Use of the VR O&M courses allows us to carry out 20 times as many tests in an hour as we’d be able to do with the physical test. Further, at the end of the testing, we have a score,” explained Dr. Bennett. “We don’t have to rely on graders to score the results, a process which also risks revealing personal identifiers. Plus, the participants really enjoy the test!”


Another benefit of virtual testing is that the subject cannot progress through the course using echolocation, which involves the use of sound and touch to move through a space in the absence of visual stimuli. Many people with low vision are able to develop this helpful navigational skill. In physical O&M courses, however, a patient’s use of echolocation can introduce confounding variables in evaluations of his or her functional vision.


As investigators anticipated, all control subjects in this study were able to successfully complete the VR O&M courses. Many patients with RPE65-associated retinal disease were also able to complete the courses, though required greater levels of arrow illuminance and object luminance, had approximately twice as many accuracy errors, and took at least twice as much time. As in clinical trials of Luxturna, the patients who received gene therapy were able to quickly and accurately navigate VR O&M courses after treatment.


These results indicate that VR O&M tests are worthwhile to explore as potential endpoints for functional vision in sighted participants, as well as patients with inherited retinal diseases. Future studies on VR O&M tests may serve to validate the protocol Drs. Aleman, Bennett, and collaborators have developed and may incorporate these tests in clinical trials to evaluate effects of experimental treatments.


Aleman TS, Miller AJ, Maguire KH, Aleman EM, Serrano LW, O'Connor KB, Bedoukian EC, Leroy BP, Maguire AM, Bennett J. A virtual reality orientation and mobility test for inherited retinal degenerations: Testing a proof-of-concept after gene therapy. Clinical Ophthalmology. 2021;15:939-952.

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