Children presenting with nystagmus can pose significant challenges for clinicians for a variety of reasons. Here, the authours discuss the diverse clinical context in which these patients present and the unique impact nystagmus has on visual function. This provides the context for a more methodical, robust approach to a core workup, adaptable to all patients and settings which can identify important red flags and direct further specialist testing. The role of conventional and nystagmus-specific treatments are discussed with particular attention drawn to the importance of ongoing education and support for patients and families.
Key points
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Nystagmus in children can present in a wide variety of clinical contexts and has a diverse range of underlying causes and symptoms.
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The approaches to managing children with nystagmus vary extensively, and limited experience and access to specialist equipment create challenges for many clinicians.
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A methodical and targeted approach to the initial investigation, using basic equipment only, can provide the necessary clues to etiology that require urgent neuroimaging and guide specialist investigations required for a comprehensive diagnosis.
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Management in the clinic consists of using a variety of conventional and more nystagmus-specific treatments to optimize vision. Understanding the impact of nystagmus on wider visual function is also crucial in maximizing real-world visual function.
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Providing information and support to patients through referrals and signposting to support networks is a crucial but often underestimated element of management.
Introduction
Nystagmus can be defined as an uncontrolled, to-and-fro eye movement initiated by a slow phase. It can be seen in the context of significant visual disability, a host of neurologic conditions, or as an isolated disorder. When clinicians are presented with a child who has possible nystagmus, the range of diagnoses are extremely broad and there is significant overlap in the features associated with different etiologies. For these reasons, children with nystagmus can pose a significant challenge to clinicians, and accordingly, management of such cases varies widely. In this article, we seek to provide clinicians with a robust toolkit for managing children with nystagmus and provide a simple, methodical workflow composed of 2 parts: the core workup (suitable for any clinician working in a modern health care setting and without specialist equipment) and the advanced workup . We focus on the identification of RED and GREEN flags which clinicians can use to identify those patients with the most pressing need for further investigation or treatment and highlight that most of these features come from the basic core history and examination, not specialist tests. The authors also detail the support and information that these children and their families should expect from a modern health care service and treatment options regardless of geographic location.
Table 1 provides a list of common nystagmus phenotypes regularly referred to in this article.
| Glossary of nystagmus types | |
|---|---|
| Infantile nystagmus syndrome (INS) | A form of nystagmus characterized by, onset between 4 and 6 mo of age, horizontal nystagmus, staying horizontal in vertical gaze, beating in the direction of gaze, dampening on convergence and associated with null zones and head postures. It can be seen in the context of nystagmus due to ocular anomalies (such as congenital cataract), in patients with albinism and as an isolated condition. When seen in a child, it makes an underlying metabolic or acquired neurologic cause unlikely. |
| Fusion maldevelopment nystagmus syndrome (FMNS), | Previously manifest latent nystagmus and caused by early loss of binocularity and seen very commonly in strabismus, congenital cataract and any cause of early visual loss. Typical clinical features include horizontal nystagmus that beats in the direction of the viewing eye with monocular occlusion and that dampens in adduction of the viewing eye. When seen in a child, it makes an underlying metabolic or acquired neurologic cause less likely. |
| Periodic alternating nystagmus (PAN) | A form of nystagmus where the direction of the fast phase changes according to a regular cycle. A variant called aperiodic PAN is also described where the pattern of cycles is less regular. Many etiologies have been described, but it is important to identify as management options are different in some cases particularly when it comes to head posture surgery. |
| Gaze-evoked nystagmus (GEN) | The most common acquired nystagmus. The nystagmus is evoked on lateral gaze but absent in primary position; it beats in the direction of gaze, similar to FMNS but is unaffected by monocular occlusion. There may (or may not) be downbeat nystagmus in lateral gaze or depression. In elevation, there may (or may not) be unsteady gaze or upbeat nystagmus. Horizontal smooth pursuit is almost always quite saccadic, which is one way to differentiate it from end-point nystagmus. It is usually caused by cerebellar lesions/malformations or drug toxicities. |
| Voluntary “nystagmus” | An infrequent but persistent cause of referrals in children. Typically, it presents as horizontal back-to-back saccades (with no slow eye movement), usually induced by convergence effort and often accompanied by mild lid closure. It is therefore not nystagmus as there are no slow phases and can be simulated in many healthy subjects. Clues to the diagnosis include miosis, lid flutter, and an inability to sustain the movements for more than 30–45 s. |
| Other forms of non-nystagmus eye movement | Similar to voluntary “nystagmus,” other eye movements masquerading as pathologic nystagmus can form part of the differential diagnosis of children with nystagmus. These include physiologic end point nystagmus (typically seen in extreme gaze angles, takes time to build up, and dampens after a few beats) and the more concerning opsoclonus (intermittent, multidirectional, back-to-back saccades best viewed after changing fixation, or on lid closure) which would typically trigger urgent workup often seeking underlying neuropathology including neuroblastoma. |
Diagnosing nystagmus
The importance of a structured workup
Nystagmus is a clinical sign, not a diagnosis. Therefore, when clinicians are presented with a child who has “nystagmus,” the range of underlying diagnoses is very broad. Indeed, they are not even limited to those causes of nystagmus but also those causes of eye movement that can look like nystagmus (eg, opsoclonus), some volitional eye movements (volitional “nystagmus”), and in some cases, normal eye movement reflexes (end-point nystagmus).
Therefore, a “battery of tests” approach to workup in all children with suspected nystagmus would be unworkable, and a more nuanced (but still simple) approach is needed.
Broadly, consensus exists that a good approach to diagnostic workup in these children is to consider it in 2 stages: the initial core workup (needing very little in the way of specialist expertise or equipment) and then the advanced workup comprising more specialist expertise and equipment as directed by the core workup.
This approach is supported by the fact that the vast majority of “red flags” that clinicians seek when managing children with nystagmus (ie, those features or findings suggesting an underlying neurologic cause or causes requiring the most urgent investigation) are found during the core workup and not identified by superspecialist investigation [ ].
In April 2023, a UK-wide group of nystagmus specialists, patient and public involvement and engagement (PPIE) representatives and stakeholders (the Nystagmus UK Eye research group) published a set of concise practice points around managing nystagmus in childhood supported by the Royal College of Ophthalmologists, United Kingdom [ ].
It can be seen from Fig. 1 that again, all the “red flags” identified in this guide for clinicians are found during the initial core workup phase of the proposed diagnostic workflow and not during the advanced workup stage or requiring any specialist equipment or expertise. All are identified by a combination of routine history taking, direct questioning, routine ophthalmic and orthoptic examination, and a basic nystagmus examination.
Clinical urgency (often a cause of anxiety for clinicians) is addressed at the core workup stage. This stage of the workup then directs more bespoke and often more specialist investigation, which may include urgent inpatient investigation, neuroimaging, specialist ophthalmic investigations including retinal optical coherence tomography (OCT) or electrodiagnostic tests (EDTs), genomic testing, and in some cases, eye movement recordings (EMRs). These additional tests and investigations would typically serve to refine a clinical diagnosis (ie, from “possible retinal dystrophy” to molecular diagnosis), be used to measure the visual disability more accurately, or identify associated disability (ie, EDTs ± MRI neuroimaging in a case with optic nerve hypoplasia), or be used to identify bespoke management strategies and treatments (ie, types of surgical intervention for head-postures caused by null zones). In developed health care systems, only under rare circumstances should local provision of these more bespoke investigations preclude access for patients or direct their use (ie, MRI being more freely available than EDTs resulting in unnecessary MRI under general anesthetic in young infants).
In the following sections, we describe a practical approach to aid clinicians in both the core workup and advanced workup and describe how a basic methodical approach can help clinicians investigate this often complex group of young patients.
Core workup
The initial workup of children referred with possible nystagmus requires only the typical expertise and equipment found in most ophthalmic departments that see children. It includes a number of elements that are routine in most eye departments with the addition of some bespoke direct questions and a methodical examination of the “nystagmus” itself. It comprises.
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History taking
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Orthoptic and ophthalmic examination
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A basic nystagmus examination
It is important to note that for many children with nystagmus, identifying the underlying cause relies on the sum of multiple small pieces of information rather than a single pathognomonic clinical sign or symptom. For this reason, documenting all the findings or “clues” during each stage of the workup can be very helpful.
History taking
For most cases presenting to an ophthalmic service, a routine history would be taken from the patient and/or their guardians and often yields important information directing further questioning and investigation. This would typically comprise.
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Presenting complaint/observation (reason for the referral)
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History of the presenting complaint/observation
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Previous ophthalmic history
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Previous general medical history (including birth and pregnancy)
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Current medications
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Family history
Open questions followed by targeted questions around each component of the basic history are key. For example, if a parent has seen uncontrolled eye movements in a child, what age did it start? (4–6 months is reassuring as it is typical for infantile nystagmus syndrome [INS]), who has noticed it (if parents do not notice it and it has been seen only at the first optician’s appointment then it may not be as acute in onset as it seems), and so forth.
Furthermore, certain visual behaviors indicative of underlying causes may be observed while taking a history or while the child is at play. These include signs such as compensatory head postures and head shaking (typically in over 1 year olds), ataxia, or poor coordination suggestive of neurologic disease or eye rubbing for retinal stimulation seen in blind infants. Light hair or skin tone, particularly in the context of the family could also be observed leading to specific questions to guardians and examination of family members for signs of mild albinism such as iris transillumination or subtle foveal hypoplasia. This can be particularly helpful in infants where cooperation is limited.
Further specific targeted questions which may be a follow-on from the basic history include asking about oscillopsia (reported rarely in congenital forms of nystagmus), nyctalopia (suggesting a rod disorder), and photophobia (seen in albinism, aniridia, and some cone disorders).
A comprehensive family history is an essential part of the initial assessment. Clues to the presence of an inherited disorder may not be obvious without direct questions about disorders of vision and “nonophthalmic” disorders in relatives due to many conditions having seemingly very different features in different family members. For example, in many families with albinism, it may be known that some relatives are photophobic, some may have strikingly different skin and hair color to their immediate family, and some may have unexplained low vision. None may have nystagmus. It, therefore, is important to ask about any medical disorders in relatives, whether they seem to be related to nystagmus or not.
If a clear family history of nystagmus is noted, identifying the structure of the pedigree, in addition to information about the clinical characteristics of those affected, is key. Elucidating the degree of visual disability and treatment history for those affected can help differentiate these groups of disorders. Drawing a family pedigree will help narrow the search for potential hereditary causes which can reduce the number of investigations required in many cases.
Orthoptic and ophthalmic examination
The orthoptic examination can be split broadly into 3 elements: a comprehensive assessment of visual function, binocular single vision (BSV), and any anomalous head posture (AHP) assessment. Tracking visual function and any amblyogenic factors is essential in ensuring that the vision is maximized during the critical period and produces the best long-term outcome. Assessing BSV is also of particular importance due to the higher prevalence of strabismus in childhood with nystagmus, reported as between 16% and 52%, dependent on the underlying cause [ , ].
Visual function
Multiple factors affect vision in patients with nystagmus, so a comprehensive assessment is essential to build a true picture of visual function. Additions to a typical assessment should include testing.
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Monocularly and both eyes open to assess “real world” vision, which can be significantly reduced on occlusion due to an increase in nystagmus intensity
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With and without AHP to assess the effect of any null zone on acuity
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Near vision and preferred reading distance vision where acuity often can improve due to a convergence null
It should be noted that the visual disability associated with nystagmus, goes far beyond static, non-time-restricted, visual acuity losses [ ]. The effects of crowding, contrast, gaze angle, variation in the nystagmus according to mood/tiredness and stress are difficult to measure and are best recorded from direct questioning until we have better measures available in the clinic. It is important to record these elements of visual function so that a simple measurement of static visual acuity recorded on a monochrome test under well-lit conditions and without time restriction doesn’t become a proxy for ‘visual function’.
Binocular single vision
A comprehensive assessment of BSV should be carried out with extra attention paid to the behavior of the nystagmus when one eye is occluded and the effects of any AHP, including:
Cover test/prism cover test: Near and distance, with and without refractive correction, and with and without AHP.
Convergence: With refractive correction and AHP. Noting near point and change in amplitude/frequency of nystagmus.
Fusion: Sensory, motor, and stereopsis. Confirming presence and level also can help confirm whether a deviation is controlled when overlying nystagmus makes cover testing more challenging.
Ocular movements:
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Extraocular muscle assessment: Versions and ductions in all positions of gaze, being careful to separate from any pseudo effects of the nystagmus on the range of movement.
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Vestibular–ocular reflex: Presence/absence and any effect on nystagmus waveform.
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Smooth pursuit: Presence/absence with a descriptive report of any abnormalities.
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Optokinetic nystagmus: Presence/absence with a descriptive report of any abnormalities such as an inverted response.
Anomalous head posture assessment
A standardized method for the objective measurement of the size of AHPs remains to be established. Objective methods that can be used for measuring AHPs include using a cervical range of motion device [ ], orthopedic goniometer [ ], torticollometer, Harms’ wall [ , ], and others. In the authors’ opinion, reliable measurements can be gained using an adjustable protractor, fixating on a target at the threshold of acuity, or using yoked prisms to shift gaze to the position at which the AHP is neutralized. For patients with INS, gaining interest with a dynamic target, such as a video, can elicit AHPs that may not be fully evident otherwise. It is important to remember that the more extreme the head posture, the greater the cost of adopting it and so the frequency with which the head posture is adopted may be more an indicator of how tolerable or uncomfortable it is. A discussion with the patient/family about the impact on daily life and any discomfort will inform whether any treatment is indicated.
Routine ophthalmic examination
An ophthalmic examination should be performed using the best age-appropriate equipment available, looking specifically for ocular signs commonly associated with nystagmus, which may include but are not limited to.
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Cornea and globe size: microphthalmia associated with coloboma, or buphthalmic eye associated with glaucoma, and so forth.
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Anterior chamber structure: anterior segment dysgenesis or PAX6 gene disorders.
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Iris structure: aniridia, coloboma, iris transillumination (eg, albinism or some PAX6 -related disorders).
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Lens: cataract, aphakia (congenital/acquired), intraocular lens implant following previous surgery, vitreous clarity (eg, vitreous hemorrhage)
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Retina and optic nerve structure: coloboma, disc anomalies (eg, papilledema, hypoplasia, coloboma, or small cup seen in albinism), retinal hypo/hyperpigmentation, and/or pigment, foveal structure (eg, hypoplasia, atrophy from congenital infection)
One particular clinical sign that is pertinent to many children with nystagmus is the foveal architecture. During the routine examination, clues often can be identified by direct visualization using an indirect or direct ophthalmoscope even if conclusive evidence is not possible. For example, foveal hypoplasia is most easily seen on OCT scanning, but this forms a part of the advanced workup and age-appropriate equipment is often not available, especially for very young infants. However, clues to its presence include lack of a typical foveal light reflex, situs inversus of the major retinal vessels, and in some cases retinal vessels which course through the center of the macula. These “clues” should be noted and inform the subsequent advanced workup and interpretation of those findings.
A basic nystagmus examination
Assessing nystagmus in children can pose a significant challenge for a variety of reasons. Identifying direction requires experience but in practice, limited cooperation and the presence of strabismus and head postures can make this even more challenging. However, by breaking the assessment down into systematic steps and focusing purely on the nystagmus, rather than any other eye movement issue, in almost all cases an informative picture of the nystagmus is ultimately achievable.
The initial task is to identify any nystagmus (or other abnormal eye movements) in the primary position. Observing the eyes “at rest” to a distance and near target initially allows an evaluation of the waveform by answering the following questions.
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Is there a slow phase (a slow eye movement rather than just fast saccades) and, therefore, is this nystagmus or not?
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Is the axis of oscillation horizontal, vertical, torsional, circumrotatory (ie, circular or elliptical), or a mixture?
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Is there an initial slow phase and corrective fast phase (jerk) or equal slow back-to-back slow phases (pendular)? Note the direction of the faster “beat”
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Is the wave the same in each eye (conjugate) or different (disconjugate)?
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How fast is the movement (frequency) and how large (amplitude)?
Spending some time looking at the bridge of the nose while assessing nystagmus can make it easier to discern these characteristics versus watching each eye individually.
The process is then repeated for the 9 cardinal positions of gaze, paying attention to any changes in the waveform and documenting the result ( Fig. 2 ). Typically, INS is horizontal and remains so in all positions but tends to increase in intensity toward the gaze direction of the beat and decreases in the opposite direction [ ]. This gives rise to a null region where the opposing directionality reduces the nystagmus to its lowest intensity (or “jerkiness”) where vision is optimized.
