Clinical highlights – November 2024
This month’s newsletter will highlight recent studies demonstrating how eye movements can support pharmaceutical research in diagnosing, monitoring neurological health, and advancing the development of new medications.
We are excited to share insights into the potential of eye tracking. Every month, we keep you updated on the latest news shared by the scientific community.
Enjoy the reading!
1. Challenges Faced in Pharmaceutical Research
Pharmaceutical companies face several substantial challenges in developing treatments for neurological conditions. These challenges can be categorized into three key areas: diagnostic difficulties, monitoring issues, and prognostic uncertainties.
To address these challenges, eye movements could offer a promising solution. With the right tool, researchers can utilize a non-invasive, quantifiable, and streamlined approach to assess these difficulties more effectively, allowing for better patient selection. Moreover, by monitoring eye movement patterns, it becomes possible to track disease progression and enhance prognostic predictions. Ultimately, eye tracking could ultimately contribute to the development of more targeted and effective treatments.
Accurate Diagnosis
Atypical parkinsonian syndromes, such as Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS) or Multiple System Atrophy (MSA), are often misdiagnosed as Parkinson’s disease (PD) due to their similarities, complicating research efforts for all three conditions.
- Currently, MSA has a misdiagnosis rate of 20% [link]. Oculomotor dysfunction is one of the key clinical features of MSA[link], and variations in oculomotor biomarkers can help in distinguishing MSA from other parkinsonian syndromes[link]. Therefore, analyzing eye movements can help lower this misdiagnosis rate, ultimately improving the statistical power of clinical trials.
- Eye movement analysis is key for accurately diagnosing PSP, as ocular motor dysfunction is the primary diagnostic criterion. This includes vertical gaze palsy (level 1), slow saccades (level 2), and frequent macro square wave jerks (level 3). Eye movement analysis holds promise for early detection of PSP, helping to reduce misdiagnoses [link]
“Clinical diagnosis of Parkinsonian syndromes can be difficult in early stages, due to the indiscriminate nature of
clinical symptomatology (akinesia, rigidity, tremor).In addition to idiopathic Parkinson’s disease (IPD), these include progressive supranuclear palsy (PSP), multisystem atrophy (MSA) and cortico-basal degeneration (CBD).
Performing oculomotor tests […] can provide strong arguments for diagnostic orientation. “
Gaymard, 2013
Why is accurate diagnosis important for clinical trials?
Numerous trials fail in Phase 3 after a successful Phase 2, primarily due to the heterogeneity of the recruited patients. As a result, accurate patient selection becomes crucial in order to replicate the successes of earlier phases.
Monitoring Disease Progression
Neurological disorders are particularly complex, with subtle symptom changes that can be overlooked if monitoring tools lack sufficient sensitivity. However, there is a growing recognition of the importance of eye movements as biomarkers, particularly for effectively monitoring disease progression and evaluating treatment efficacy in these disorders.
“Oculomotor studies provide an ideal neuroscience model to investigate the association between brain
mechanisms and behavior”Eckstein et al., 2017
- Eye movement parameters, such as blink rate, serve as critical outcome measures in studies focused on L-Dopa-induced dyskinesia in Parkinson’s disease, providing valuable insights into treatment responses [link]
- In the RT001 clinical trial for progressive supranuclear palsy (PSP), the ocular motor section of the PSP Rating Scale evaluates the impact of treatment on eye movement dysfunction, further demonstrating the utility of these parameters in clinical assessments [link 1] [link 2]
- Eye movements are employed as primary outcome measures in treatments for internuclear ophthalmoplegia (INO) associated with multiple sclerosis (MS)[link], with increasing evidence supporting their role in investigating the outcomes of remyelinating therapies [link]
Why is monitoring the disease important for clinical trials?
Clinical scales may overlook subtle disease evolutions. Therefore, a fine monitoring of disease progression is crucial in clinical trials, as it enables researchers to assess treatment efficacy, identify adverse effects, and validate biomarkers that can indicate how well a treatment is working.
Prognostic Predictions
Prognostic predictions play a crucial role in managing neurological diseases, allowing for earlier interventions and tailored treatment strategies.
- For example, research shows that eye movements can identify gait freeze—one of the most distressing symptoms of Parkinson’s disease—up to five years before clinical symptoms manifest [link]
- Similarly, in multiple sclerosis (MS), eye movements are being explored as a means to predict disability levels [link]. Current investigations focus on using these movements to track disease progression and assess cognitive impairment[link]
- Furthermore, for Alzheimer’s disease, eye movements can effectively differentiate between amnesic mild cognitive impairment (aMCI) and non-amnesic mild cognitive impairment (naMCI). Since aMCI often progresses to Alzheimer’s while naMCI is associated with other forms of dementia, this distinction is vital for timely intervention and care planning [link]
How can prognostic predictions help with research for treatment?
In slowly evolving pathologies, it may be important to identify patients with more rapid evolution. Consequently, accurate prognostic predictions are essential for developing targeted therapies and improving patient outcomes. Moreover, eye movements serve as a non-invasive, early biomarker that enhances the ability to forecast disease trajectories.
2. Gain Insight into Neurotransmitter Mechanisms
There is increasing evidence of the relevance of eye movements as sensitive biomarkers in the mechanisms of cognition and their pharmacology.
Here are two non-exhaustive examples:
- In GABAa modulation, saccadic eye movements have been measured to examine benzodiazepine receptor sensitivity in anxiety disorders [link]
- More recently in dopaminergic receptors, the impact of a dopamine agonist on saccadic eye movements has demonstrated an increase in motivational vigour, showing promise in the treatment of depression [link].
Eye movements can support pharmaceutical research. By analyzing eye movement patterns, clinicians can assess damage at the neurotransmitter level and its location. Specifically, abnormalities in eye movements offer clues about which areas of the brain are affected, making them a useful tool for diagnosing and monitoring neurological diseases, guiding treatment strategies, and evaluating disease progression.
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