Eye Movements Revolutionize Drug Development for Neurodegenerative Diseases

The development of new drugs for neurodegenerative diseases is facing significant obstacles, particularly the slow and subjective nature of traditional clinical endpoints. Conditions such as Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer’s disease (AD) often rely on assessment scales that overlook subtle changes. This oversight can lead to lengthy clinical trials, resulting in high costs and delayed access to vital therapies for patients.

A promising alternative has emerged: measuring eye movements. This approach offers a fast, objective, and sensitive method to track changes in the central nervous system (CNS) during disease progression. With current technology, eye movements can be assessed within minutes using standard laptops or webcams, making them practical tools for clinical trials. Integrating these measures into existing workflows provides a reliable method for monitoring disease progression over time.

Eye movements have long been described as “the window to the brain.” They are closely linked to neural circuitry, with different types of movements indicating various aspects of neurological function. For instance, saccades and antisaccades reflect attention and inhibition control, while smooth pursuit engages cortical and cerebellar networks. Fixation stability involves widespread cortical and brainstem systems. Abnormalities in these oculometric measures have been documented across disorders like PD, ALS, and MS.

Recent advancements mean measuring eye movements no longer requires specialized laboratories or equipment. A brief test utilizing a laptop and webcam can now quantify movement parameters through computer vision algorithms, significantly reducing the burden on clinical sites, especially in multicenter trials. Several studies have successfully employed this technology to assess eye movements outside laboratory settings, yielding promising results.

For example, in a clinical trial focused on Parkinson’s disease, replacing a 21-month motor scale endpoint with a nine-month eye movement measure reduced the required participant count from 360 to 140 per trial arm. Similarly, a Phase IIb trial in ALS demonstrated progressive fixation instability that aligned with disease worsening over a 12-month period. These findings highlight the potential of eye movements as a valuable endpoint, enhancing trial efficiency and providing a biomarker for tracking progression.

Regulatory agencies are increasingly supportive of incorporating additional endpoints in CNS trials, including digital health technologies (DHT). The U.S. Food and Drug Administration (FDA) has issued guidance emphasizing the importance of integrating validated and reliable endpoints, like eye movement measures, into clinical trials. This creates a pathway for sponsors to introduce these metrics as exploratory endpoints, with future qualification potential.

The landscape of clinical trials is evolving, with various biomarkers being adopted to complement traditional assessment scales. Eye movement metrics are particularly well-suited for this shift due to their objective nature, ease of measurement, and scalability across diverse trial environments. The convergence of regulatory support and operational innovation presents an opportune moment to integrate eye movement biomarkers into CNS drug development.

To begin this integration, sponsors can incorporate eye movements as biomarkers in early-phase studies by adding oculometric endpoints alongside standard assessments. This simultaneous collection of data enhances the evidence base while mitigating risks. A core set of tailored oculometric measures, such as saccades, pursuit, and fixation tasks, ensures consistency across sites and studies. Predefined workflows will facilitate reproducible extraction of metrics, with robust governance for storage and analysis.

Sponsors should specify hypotheses regarding the clinical relevance of eye movement metrics, correlating them with clinical anchors, participant stratification, and early disease progression detection. Engaging transparently with regulators can streamline the transition from exploratory usage to accepted endpoints.

Looking ahead, clinical sites could incorporate eye movements in drug trials as endpoints within a year. This integration would involve simplified workflows, brief oculometric assessments, and reproducible setups. Participants would benefit from a seamless experience, free from complex devices and lengthy procedures. Regulators and payers would gain access to comprehensive evidence packages that merge established scales with objective eye movement measures. Such packages will not only support trial claims but also inform real-world coverage decisions through their sensitivity to disease progression.

The broader research community stands to benefit from enriched datasets, facilitating secondary analyses and insights across different diseases. Achieving this vision is feasible within current trial infrastructures, provided all stakeholders commit to integrating eye movement endpoints promptly.

The CNS field is in urgent need of biomarkers that are sensitive, objective, and practical. Eye movement measures are ready to meet this demand, serving not only as innovative solutions but as currently available tools. By adopting eye movement assessments as exploratory endpoints, sponsors can shorten trial timelines, reduce sample sizes, decrease risks, and enhance decision-making. Clinical sites can operate more efficiently, regulators can receive improved evidence, and patients can gain faster access to effective treatments. The industry should recognize oculometric measures as essential components in CNS trials: scientifically robust, easy to implement, and aligned with existing regulatory frameworks. Broader adoption of these measures could transform the pace of drug development, delivering life-changing therapies to patients more swiftly.