Eye Movement Findings Reframe Amblyopia as a Binocular Disorder

Most ophthalmologists think of amblyopia in terms of reduced visual acuity in one eye and impaired stereopsis. But those deficits alone do not explain how patients function in the real world.

“We are increasingly recognizing that amblyopia is not a monocular problem,” says pediatric ophthalmologist Fatema Ghasia, MD, Director of the Ocular Motility and Visual Neurosciences Lab at Cleveland Clinic Cole Eye Institute. “It’s actually a binocular disorder with a constellation of visual sensory deficits and eye movement abnormalities.”

Two recent studies from the Cole Eye Institute offer new insight into amblyopia. The findings show that fixation and saccadic abnormalities persist during binocular viewing and that nystagmus plays a major role in ocular motor behavior.

Amblyopia affects an estimated 3% to 5% of the U.S. population, and delayed detection can result in lifelong visual impairment. Standard clinical testing remains largely monocular, even though most real-world visual function is binocular.

According to Dr. Ghasia, ocular motor abnormalities may help explain why some patients continue to struggle with reading, visual scanning and other visuomotor tasks despite standard treatment for amblyopia.

Fixation instability may be an objective marker of amblyopia severity

In a recent study published in the Investigative Ophthalmology & Visual Science special issue on nystagmus co-edited by Dr. Ghasia, Dr. Ghasia and colleagues used video-oculography to characterize fixation eye movement abnormalities in healthy controls (n = 64) and patients with amblyopia and/or strabismus (n = 97), both with and without nystagmus. The study provided new insights into the relationship between fixation stability and visual function.

Three findings were especially notable:

• Amblyopia produced asymmetric fixation abnormalities between the two eyes. In patients with amblyopia, fixation instability was greater in the amblyopic eye during amblyopic-eye viewing than in the fellow eye during fellow-eye viewing. In other words, the amblyopic eye was not only sensory impaired but also less stable during fixation. By contrast, patients with strabismus but no amblyopia did not demonstrate the same interocular asymmetry. This suggests that this pattern is specifically associated with amblyopia rather than ocular misalignment.
• Fixation dysfunction tracked with amblyopia severity. Worse amblyopia was associated with greater fixation instability, supporting the idea that ocular motor dysfunction reflects the degree of underlying sensory loss.
• Nystagmus worsened fixation instability, but did not fully account for it. Among patients with nystagmus, those with treated or mild strabismic amblyopia had better fixation than those with moderate or severe strabismic amblyopia. This suggests that although nystagmus is an important contributor, the severity of amblyopia independently predicts the degree of fixation disruption.

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Graphs show extent of fixation instability in both eyes when viewing with fellow eye (left) and amblyopic eye (right). The focal target is marked with a black cross. Fixational eye movement of the fellow eye is represented in blue; fixational eye movement of the amblyopic eye is represented in red.

These findings suggest that interocular differences in fixation stability could serve as objective biomarkers of amblyopia severity.

“From a screening perspective, we potentially can look at the interocular difference in fixation stability and identify a child more likely to have amblyopia,” Dr. Ghasia says. “That could be very valuable for young patients not yet able to read an eye chart. We could possibly detect amblyopia earlier so we can begin treating it earlier.”

Nystagmus is a key determinant of saccades

In a second study, also published in Investigative Ophthalmology & Visual Science, Dr. Ghasia and colleagues used video-oculography to measure visually guided saccades (rapid eye movements made to peripheral targets) during binocular and monocular viewing in patients with healthy eyes (n = 21) and in patients with amblyopia and/or strabismus (n = 49).

The data revealed that some abnormalities tracked with amblyopia severity, while others were driven primarily by nystagmus.

• Saccadic latency was most closely linked to amblyopia severity, particularly during amblyopic-eye viewing.
• Saccadic inaccuracy was more strongly associated with nystagmus. Although normal saccades may be followed by a corrective movement, patients with amblyopia and strabismus often required multiple corrective saccades to acquire the target. This was especially common in patients with nystagmus.

Notably, the basic mechanics of saccade generation remained intact across groups. This suggests the deficits arise from abnormal sensory processing and disrupted binocular development rather than a motor abnormality.

“Studies often exclude patients with nystagmus or do not analyze them separately,” Dr. Ghasia says. “Now we know that nystagmus should not be ignored in studies of amblyopia and strabismus.”

How amblyopia, strabismus and nystagmus contribute to abnormal eye movements

Together, the two studies help clarify how amblyopia, strabismus and nystagmus each contribute to abnormal eye movements.

The key takeaways are:

• Amblyopia and strabismus affect both gaze holding and gaze shifting.
• Nystagmus significantly influences ocular motor behavior.
• Ocular motor dysfunction is driven, in part, by sensory loss from amblyopia.
• The most severe ocular motor deficits occur in patients with strabismic amblyopia and nystagmus.

These findings have important clinical implications. They suggest that ocular motor abnormalities in amblyopia are not a single entity.

Potential implications for screening and monitoring

These findings do not yet change routine clinical care, but they strengthen the rationale for incorporating eye movement analysis into future approaches to amblyopia diagnosis and follow-up.

“Eye tracking offers an objective, nonverbal, pediatric-friendly way to capture fixation and saccadic behavior,” Dr. Ghasia says. “This is important because current instrument-based screening tools primarily identify amblyopia risk factors, such as anisometropia and strabismus, but have limited specificity for detecting amblyopia itself. As a result, many children are referred for further evaluation despite not having amblyopia.”

Eye movement markers could improve specificity when used alongside conventional screening tools, she adds. Some eye-tracking platforms use animated targets to engage children as young as age 2, allowing clinicians to assess gaze behavior, fixation and saccades.

As eye-tracking technology becomes more portable and less expensive, its use outside research settings may become more feasible. Over time, this may support broader adoption of eye tracking for amblyopia detection and monitoring, particularly when paired with artificial intelligence.

“I am more and more convinced that eye movements can become useful clinical biomarkers for diagnosis and monitoring of amblyopia,” Dr. Ghasia says. “Now we know that nystagmus, which is an objective finding, can indicate worse outcomes for a patient with amblyopia or strabismus. Those are the people who likely will have more real-world visual impairment with both-eye viewing, even after treatment.”