A Window into the Eyes: Using Ocular Biomarkers to Track Progression in Huntington’s Disease

When caring for people affected by Huntington’s disease (HD), doctors often face major challenges due to the lack of precise tools to track how the disease progresses or to predict exactly when a person carrying the gene will start showing symptoms. The standard medical rating scales used today are not sensitive enough to detect very early changes during the premanifest stage, which limits how well individuals can be helped before they start showing movement difficulties.

Because the eye is actually an extension of the brain and nervous system, researchers at the University of Cambridge have looked into whether checking problems with the eyes (called ‘ocular abnormalities’ in medical lingo), and specifically looking at the structure of the retina and the way the eyes move, could act as a reliable biological marker (or ‘biomarker’) for people with HD. Their review article, recently published in the Journal of Neurology, systematically examined the literature on this topic.

In the review, the authors focused on two main areas: Optical Coherence Tomography (OCT), which is a way of taking detailed scans of the back of the eye, and oculomotor assessment, which measures how the eyes move. The goal was to see if these non-invasive eye tests could help doctors diagnose the disease earlier or track its severity more accurately than current methods.

Retinal Scans

The first major area of investigation involved the structure of the retina, the layer at the back of the eye which captures light like a camera sensor, and which contains nerve cells that are similar to those in the brain. Since we know that HD kills brain cells, one theory is that it might also cause thinning in the nerve layers of the retina, which can be measured by OCT. However, the review found that, while some studies did detect thinning in the retinal nerve fibre layer, particularly on the temporal side (the side closest to the ear), the evidence was not consistent across all investigations. For example, out of ten studies looking for this specific thinning, only five found it to be statistically significant. Some studies found that the retinal layers were thinner in patients who had more severe disease symptoms, suggesting a possible link between eye structure and brain health, but other large studies found no significant thinning at all.

The inconsistency continued when researchers looked at the macula, which is the central part of the retina responsible for making sure our vision is sharp. While a few studies reported the macula was thinner or less voluminous in HD patients, many others found no changes. Some studies also investigated changes in the density of small blood vessels in the eyes, but the findings were similarly inconsistent. Overall, while exams of the retina show some potential, the fact the evidence from different studies seems to point to different conclusions, makes it difficult to use them as a reliable way to diagnose or track the HD right now.

Eye Movements

The second major area of focus in the review was eye movements, or ‘oculomotor function’. Researchers can use special eye-tracking cameras to check how fast and accurately a person can look at a target and measure ‘saccades’, which are the rapid eye movements used to jump focus from one object to another. As we know, HD causes involuntary movements of the body; however, this can often extend to the movement of the eyes. The review found that, unlike the mixed results from eye scans such as OCT, the studies on eye movements provided much clearer and more consistent evidence. 

More specifically, the review highlighted that people with HD often have trouble initiating eye movements due to something called ‘prolonged latency’ – that is, their brain takes longer to tell their eyes to move towards a target. Once the eyes do move, they often travel slower than normal (‘reduced velocity’). Importantly, these problems are not only present in people who have motor difficulties but can also be detected in premanifest individuals who carry the gene but do not yet show major physical symptoms. This suggests that eye tracking could be a useful way to spot the disease early.

With regard to this, a particularly helpful test involves people to look away from a light that flashes on a screen (‘anti-saccades’). As the natural reflex in humans is to look at the light, looking away requires the brain to suppress that reflex and plan a movement in the opposite direction. People with HD can struggle with this, making make more errors and often looking at the light instead of away from it. This shows an impairment in the brain’s ability to control impulses and, as the disease gets worse, these errors happen more frequently, making it a potentially good way to track how fast the disease is progressing.

Other Eye Manifestations

A number of other eye manifestations were discussed in the review. For instance, when asked to read or visually scan a picture, patients with HD use fewer and less efficient eye movements, often taking a more chaotic path to look at the image. People with HD also have trouble maintaining a steady gaze (‘fixation’) as they get distracted more easily. Even tasks involving visual memory, where a person has to remember where a light flashed, showed that patients had less accuracy and slower reaction times.

Limitations of this study

Despite some promising findings regarding eye movements, a number of limitations need to be considered. For instance, the reviewer pointed out that measuring these tiny changes requires specialised, expensive equipment that most clinics are unlikely to have. Furthermore, factors such as fatigue, medication, and mood can affect a person’s performance on these tests, adding ‘noise’ to the data. Another limitation is that most studies only looked at patients at a single point in time rather than following them over many years, which prevents researchers from tracking the same people as they move from the premanifest to the manifest stage. 

Take-Home Message

The review suggests that tests and exams involving the eyes hold significant promise as a source of biomarkers for people with HD, but they are not quite ready for everyday clinical use. Between the two main methods analysed, tracking eye movements appears to be more reliable and consistent than taking pictures of the retina, as eye movement tests can detect abnormalities early and seem to worsen as the disease progresses –exactly what a good biomarker should do. However, eye-tracking technology is very expensive and unlikely to be available to everyone. Future research should focus on increasing accessibility and standardising how these tests are done, so that results can be compared easily between different clinics. Long-term studies that follow gene carriers over years are also needed to confirm whether eye changes can truly predict the onset and trajectory of HD. 

Summary

• Current tools fail to effectively predict HD’s onset or track early progression.
• Researchers reviewed whether the eyes could provide reliable biomarkers.
• Retinal scans showed inconsistent results and are currently unreliable for diagnosis.
• Eye movement tracking showed more consistence and promise, detecting abnormalities even in premanifest carriers.
• Despite potential, the required technology is expensive, and results can be affected by other factors such as fatigue.