The assessment of therapies and treatments for inherited retinal disorders (IRDs) heavily relies on clinical trials in ophthalmology, with mobility testing being a key part. These tests evaluate a patient’s ability to navigate their surroundings and are often done using physical mazes. However, there is a need for standardized mobility tests to ensure consistency and accuracy across different trials.
Virtual reality (VR) mazes have emerged as a promising alternative to physical mazes in mobility testing. These innovative tools simulate real-world environments using goggles, foot trackers, and hand trackers. They offer controlled conditions, the ability to test various patterns, and ensure reliability and participant safety. Studies have shown that VR protocols can effectively differentiate between IRD patients and individuals with normal sight, making them a potential standard for clinical trial effectiveness.
To validate the effectiveness of VR mazes as assessments of IRD, a comparison with physical mobility tests is necessary. Researchers have already found that VR mazes can assess mobility in patients with RPE65-associated LCA, showing improvements in speed, accuracy, and lighting requirements. However, it is essential to validate these findings by assessing both physical and VR mobility tests in the same population.
Standardized mobility tests play a crucial role in ensuring consistent and reliable results across different IRD clinical trials. Therefore, collaboration among the ophthalmology community and professional organizations is necessary to establish a standardized test that measures a patient’s ability to perceive their surroundings and incorporates various vision aspects. This collaboration would enhance the accuracy of clinical trial outcomes and facilitate the development of effective treatments.
In order to encourage more IRD trials without delays, specific and standardized guidance from the FDA on IRD endpoints is necessary. The FDA has limitations on its resources, and refining its guidance regarding human gene therapy for retinal disorders to specify preferred mobility test parameters for clinical endpoints would provide clarity for researchers. Additionally, the FDA has expressed openness to collaborating on endpoints, which could foster greater coordination between regulatory authorities and the ophthalmology community.
The Multi-Luminance Mobility Test (MLMT) has proven to be a critical tool in evaluating the effectiveness of voretigene neparvovec, a gene therapy for IRD patients. This test assesses a patient’s performance in low and moderate light conditions and has shown improved outcomes in patients with LCA and RP. Its inclusion in clinical trials has contributed to the FDA’s approval of voretigene neparvovec based on structural endpoints, without requiring a functional endpoint.
Beyond clinical trials, mobility testing has real-world applications in assessing an individual’s ability to navigate streets or operate a vehicle. Functional tests that translate into real-world activities provide added benefits in understanding the impact of IRDs on daily life. Furthermore, mobility testing can be used to measure clinical trial outcomes in specific IRD patient populations, such as those with GUCY2D and CEP290 mutations or patients with nystagmus who struggle to focus on a perimetry target.
In conclusion, advancements in mobility testing, particularly with the introduction of VR mazes, are revolutionizing the evaluation of inherited retinal disorders in clinical trials. Standardized mobility tests, collaboration between the ophthalmology community and regulatory authorities, and the inclusion of functional endpoints are all crucial elements in driving progress in this field. With the potential for improved accuracy, reliability, and real-world applicability, mobility testing holds great promise in enhancing the development of effective treatments for inherited retinal disorders.