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Study backs viability of VR paradigm for orientation, mobility testing


According to investigators, the virtual reality option could overcome hurdles associated with reliance on a physical course.

Reviewed by Tomas S. Aleman, MD

Measures of functional vision, which refers to a person’s ability to use vision to perceive the environment and function in daily life, are needed to establish benefit of novel gene therapies for inherited retinal dystrophies (IRDs). To that end, a novel standardized orientation and mobility (O&M) course, the multiluminance mobility test (MLMT), was developed and validated to assess the response to treatment with AAV2-hRPE65 for patients with vision loss due to biallelic mutations in RPE65.

Researchers are now working to develop a virtual reality orientation and mobility (VR-O&M) test that could overcome the practical challenges associated with reliance on a physical course. In a recently published paper, Tomas S. Aleman, MD, and colleagues reported on a study that provided proof-of-concept data supporting the use of a VR-O&M system to evaluate the potential for functional vision improvement using investigational therapies for IRDs.1

“Our initial findings support further investment in time and resources to refine and validate the VR-O&M technique as an alternative to physical mobility courses,” said Aleman, Irene Heinz-Given and John LaPorte Research Associate Professor in the Department of Ophthalmology at the Perelman School of Medicine, University of Pennsylvania in Philadelphia.

“Once basic VR-O&M tests are validated, the limitations of the current designs, such as lack of standardization and the inability of the VR instruments to explore the full range of our visual abilities, will need to be addressed,” he said.

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Aleman said plans were being made to evaluate the effects of gene therapy in an ocular disease, such as RPE65-LCA. It became obvious that a measure of the patient’s real-life behavior was desirable and needed for endorsement of the safety and efficacy of the treatment by regulatory bodies, such as the FDA. The idea of the MLMT obstacle course was pursued as a paradigm that could determine whether the treatment had a positive effect on visual behavior in a real-world simulated environment.

The course requires availability of a large space that is not available in most eye clinics. In addition, assembling the course is time-consuming and not easy.

Limitations for modifying luminance and obstacle size and position in ways that will accommodate testing of the diverse patterns of visual dysfunction and spectrum of severity of vision loss in patients with IRDs is another drawback of a physical course. Furthermore, test performance scoring is done manually by observers who review videos of the testing. The process is time-consuming and the observers must be masked to avoid bias, as patient confidentiality is not maintained in the recording.

A VR solution

A VR-O&M test using a commercially available headset and custom-designed software was pursued as a more flexible alternative.

“A VR testing paradigm requires a much smaller physical space, allows the opportunity for easily introducing virtually unlimited number of environmental modifications, and performance parameters are automatically detected and quantified,” Aleman said. He added that the testing still involves a patient walking through a physical space, but the required area is much smaller than with the MLMT.

Design and assessment

In developing the software for the VR-O&M, Aleman and colleagues evaluated several different configurations in cohorts of both normally sighted control subjects and patients with RPE65-associated Leber congenital amaurosis (LCA). The test itself is similar to the MLMT, as it requires patients to follow arrows through a course while avoiding collisions with randomly placed obstacles. Subjects are fitted with hand trackers and foot trackers to record information. Performance on the VR-O&M course is scored based on the number of collisions and time taken to reach the course exit.

After testing the various configurations, a protocol was selected for further evaluation in 3 patients with RPE65-LCA, including 2 patients who performed the testing before and after receiving gene therapy. Results from the controls and the patients with LCA from testing done prior to gene therapy showed differences between the 2 groups in the illumination level needed to navigate the obstacle course as well as in the number of collisions that occurred and total time needed for completing the course.

Compared with their pretreatment performance, the patients who were retested after receiving gene therapy demonstrated improvements in required illumination, number of collisions, and total navigation time that corresponded with their improvements in cone- and rod-mediated sensitivities.

Tomas S. Aleman, MD

E: aleman@pennmedicine.upenn.edu

Aleman is a coauthor on intellectual property describing the virtual reality mobility test (PCT/US2019/ 029173 pending). He has no other relevant financial interests to disclose.


1. Aleman TS, Miller AJ, Maguire KH, et al. A virtual reality orientation and mobility test for inherited retinal degenerations: testing a proof-of-concept after gene therapy. Clin Ophthalmol. 2021;15:939-952. doi:10.2147/OPTH.S292527

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