Ophthalmology – Congenital / Infantile Nystagmus

Basics

Description

Infantile nystagmus is an involuntary, rhythmic oscillation of the eyes beginning in early infancy, usually within the first 6 months of life.

The preferred modern term is:

Infantile nystagmus syndrome (INS)

rather than “congenital nystagmus,” because the nystagmus is often not present at birth and becomes apparent several weeks later.

It may occur:

• As an isolated ocular motor disorder
• Secondary to reduced visual input
• In association with albinism
• With retinal or optic nerve disease
• With strabismus
• As part of a neurologic or genetic syndrome

Epidemiology

Infantile nystagmus is uncommon.

Idiopathic infantile nystagmus has historically been estimated at approximately:

1 in 2,500–3,000 individuals

The overall prevalence of nystagmus, including sensory and strabismus-associated forms, is higher.

Major Categories

Important causes of nystagmus beginning in infancy include:

• Infantile nystagmus syndrome
• Sensory-deficit nystagmus
• Fusion maldevelopment nystagmus syndrome
• Spasmus nutans
• Neurologic nystagmus
• Vestibular nystagmus
• Drug- or toxin-induced eye oscillations

Risk Factors and Associations

Associated conditions include:

• Poor vision from infancy
• Albinism
• Foveal hypoplasia
• Retinal dystrophy
• Congenital stationary night blindness
• Optic nerve hypoplasia
• Congenital cataract
• Corneal opacity
• Childhood glaucoma
• Strabismus
• Developmental delay
• Neurologic abnormalities
• Chromosomal or genetic syndromes
• Family history of nystagmus

Genetics

Infantile nystagmus may occur with several inheritance patterns.

The best-established isolated nystagmus gene is:

FRMD7

which causes an X-linked form of infantile nystagmus.

Other genetic causes may be associated with:

• Albinism
• Retinal dystrophies
• Congenital stationary night blindness
• Foveal hypoplasia
• Developmental syndromes

For example:

GPR143 mutations cause X-linked ocular albinism and may be associated with infantile nystagmus.

Genetic counseling should be considered when there is:

• Positive family history
• Albinism
• Retinal dystrophy
• Syndromic features
• Unexplained infantile nystagmus

Pathophysiology

Stable fixation depends on accurate interaction between:

• Visual sensory input
• Ocular motor calibration
• Fixation control systems
• Vestibular pathways

Infantile nystagmus may develop because of either:

• Primary instability of ocular motor control
• Poor visual input during early visual development

There is no single mechanism explaining all cases.

Sensory-Deficit Nystagmus

Severe reduction of vision early in life can prevent normal calibration of ocular motor control.

Possible causes include:

• Bilateral congenital cataract
• Corneal opacity
• Severe retinal dystrophy
• Albinism
• Foveal hypoplasia
• Optic nerve hypoplasia
• Congenital glaucoma

The worse the early visual deprivation, the greater the risk of nystagmus.

Infantile Nystagmus Syndrome

INS usually becomes noticeable between approximately:

6 weeks and 6 months of age

Typical characteristics include:

• Horizontal oscillation
• Usually conjugate
• May be pendular early and develop jerk waveforms later
• Intensity varies with gaze position
• Often decreases with convergence
• Usually increases with fixation effort or stress
• Often has a null point

Null Point

The null point is the gaze position in which nystagmus intensity is lowest and visual acuity is often best.

A patient may adopt an abnormal head posture to place the eyes in the null position.

Examples include:

• Face turn
• Chin elevation
• Chin depression
• Head tilt

Foveation

Visual acuity in infantile nystagmus depends less on movement amplitude alone and more on periods during which the eyes remain close to the target.

These relatively stable periods are called:

Foveation periods

Longer and more accurate foveation generally corresponds with better vision.

Oscillopsia

Patients with infantile nystagmus usually do not experience oscillopsia, because the developing brain adapts to the eye movements.

Oscillopsia developing later should raise concern for:

• New acquired nystagmus
• Change in the pre-existing nystagmus
• Neurologic disease

History

Important questions include:

• Age when nystagmus was first noticed
• Progression or change
• Family history
• Abnormal head posture
• Photophobia
• Night blindness
• Better vision in dim or bright conditions
• Developmental delay
• Neurologic symptoms
• Previous brain injury
• Medications or toxin exposure

Photophobia

Photophobia may suggest:

• Albinism
• Achromatopsia
• Cone dystrophy
• Foveal hypoplasia
• Other cone dysfunction disorders

Night Vision Symptoms

Poor night vision may suggest:

• Congenital stationary night blindness
• Rod-cone dystrophy

Better vision in dim illumination with severe photophobia may occur in:

• Achromatopsia
• Cone dysfunction

Physical Examination

A full examination should assess:

• Best-corrected visual acuity
• Cycloplegic refraction
• Pupils
• Ocular alignment
• Motility
• Anterior segment
• Optic nerve
• Retina
• Fovea

Also assess:

• Head position
• Developmental status
• Neurologic examination when indicated

Characterizing the Nystagmus

Document:

• Direction
• Amplitude
• Frequency
• Pendular versus jerk waveform
• Conjugacy
• Symmetry
• Effect of gaze
• Effect of convergence
• Effect of monocular occlusion
• Null position
• Associated head posture

Direction

Classic INS is usually:

Horizontal

even in vertical gaze.

Predominantly vertical or torsional infantile nystagmus is less typical and should raise concern for neurologic or structural disease.

Effect of Convergence

Many patients with INS have reduced nystagmus intensity during:

Convergence

This can improve near visual acuity.

Strabismus

Strabismus is common in children with nystagmus.

Possible associations include:

• Infantile esotropia
• Sensory strabismus
• Albinism
• Poor visual acuity

Fusion Maldevelopment Nystagmus Syndrome

Previously called:

• Latent nystagmus
• Manifest latent nystagmus

It is strongly associated with:

• Infantile strabismus
• Disrupted binocular development

Characteristics include:

• Jerk nystagmus
• Increased intensity when one eye is covered
• Fast phase toward the viewing eye
• Direction reverses when fixation switches between eyes

Spasmus Nutans

Spasmus nutans usually begins during the:

First year of life

The classic triad is:

• Nystagmus
• Head nodding
• Abnormal head posture

The nystagmus is often:

• Fine
• High frequency
• Low amplitude
• Asymmetric
• Sometimes apparently monocular

Natural History of Spasmus Nutans

Typical spasmus nutans is usually benign and often improves spontaneously during early childhood.

However, atypical cases require evaluation for structural disease.

When Spasmus Nutans Is Concerning

Consider MRI when there is:

• Truly monocular nystagmus
• Marked asymmetry
• Optic nerve abnormality
• Visual loss
• Developmental delay
• Neurologic signs
• Persistent or progressive course
• Atypical age of onset

Rare parasellar, optic pathway, or chiasmal lesions may mimic spasmus nutans.

Albinism

Nystagmus is common in:

• Oculocutaneous albinism
• Ocular albinism

Associated ocular findings include:

• Iris transillumination
• Foveal hypoplasia
• Reduced pigmentation
• Optic pathway misrouting
• Strabismus
• Photophobia

Visual Evoked Potentials in Albinism

Multichannel VEP testing may demonstrate:

Excessive crossing of optic nerve fibers at the chiasm

and can support the diagnosis of albinism in selected uncertain cases.

It is not required in every typical case.

Congenital Stationary Night Blindness

CSNB is an important cause of infantile nystagmus when the fundus appears relatively normal.

Patients may have:

• Night blindness
• Myopia
• Strabismus
• Infantile nystagmus

Diagnosis is often established with:

Electroretinography

Diagnostic Testing

Cycloplegic Refraction

This is essential because correcting refractive error may significantly improve visual function.

Common refractive abnormalities include:

• Astigmatism
• Myopia
• Hyperopia

Optical Coherence Tomography

OCT is extremely useful for detecting:

• Foveal hypoplasia
• Macular dystrophy
• Retinal structural abnormalities
• Optic nerve pathology

Handheld OCT may be useful in young children.

Electroretinography

ERG should be considered when:

• Vision is reduced without clear structural explanation
• Retinal dystrophy is suspected
• CSNB is suspected
• Cone dysfunction is suspected

Visual Evoked Potentials

VEP may be useful for:

• Suspected albinism
• Visual pathway dysfunction
• Selected infants who cannot provide behavioral visual responses

Eye Movement Recording

Video-oculography or formal eye movement recording can characterize:

• Waveform
• Foveation
• Null point
• Frequency
• Amplitude

It is most useful in complex diagnostic or surgical planning cases.

Neuroimaging

MRI is not routinely necessary for a neurologically normal child with typical horizontal infantile nystagmus and an identifiable ocular or genetic cause.

MRI should be considered for:

• Vertical nystagmus
• Torsional nystagmus
• Markedly asymmetric nystagmus
• New or changing nystagmus
• Optic nerve hypoplasia
• Neurologic abnormalities
• Developmental regression
• Seizures
• Abnormal head circumference
• See-saw nystagmus
• Opsoclonus
• Suspected intracranial lesion

Opsoclonus

Opsoclonus is not true nystagmus.

It consists of:

• Chaotic
• Multidirectional
• Back-to-back saccades

In a child, opsoclonus should raise concern for:

• Neuroblastoma
• Postinfectious or autoimmune encephalopathy

This requires urgent systemic and neurologic evaluation.

Differential Diagnosis

Important differential diagnoses include:

• Infantile nystagmus syndrome
• Sensory-deficit nystagmus
• Fusion maldevelopment nystagmus syndrome
• Spasmus nutans
• Albinism
• CSNB
• Retinal dystrophy
• Optic nerve hypoplasia
• Congenital cataract
• Congenital glaucoma
• Gaze-evoked nystagmus
• Vestibular nystagmus
• Brainstem or cerebellar disease
• Intracranial tumor
• Drug- or toxin-induced eye oscillation
• Opsoclonus

Treatment Principles

Treatment goals are to:

• Maximize visual acuity
• Correct refractive error
• Treat amblyopia
• Improve ocular alignment
• Reduce abnormal head posture
• Improve foveation
• Treat the underlying ocular disorder

The objective is generally not to eliminate all visible nystagmus.

Refractive Correction

Accurate refractive correction is one of the most important interventions.

Options include:

• Spectacles
• Contact lenses

Contact lenses may sometimes provide better vision because:

• They move with the eye
• They reduce optical aberrations during eye movement
• Some patients experience modest reduction of nystagmus intensity

Amblyopia Treatment

Amblyopia should be treated when present.

Treatment may include:

• Optical correction
• Patching
• Atropine penalization when appropriate

Treatment decisions should account for associated strabismus and visual potential.

Treatment of Underlying Disease

Correct treatable visual deprivation as early as possible.

Examples include:

• Congenital cataract surgery
• Glaucoma treatment
• Corneal rehabilitation
• Appropriate retinal treatment

Early intervention is especially important during the sensitive period of visual development.

Photophobia Management

Patients with albinism or cone dysfunction may benefit from:

• Tinted lenses
• Photochromic lenses
• Sunglasses

These improve comfort but do not directly cure nystagmus.

Prism Treatment

Prisms may be useful in selected patients.

To shift the eyes toward the null point

Prisms can reduce the abnormal head posture.

To stimulate convergence

Base-out prisms may reduce nystagmus in patients whose nystagmus dampens with convergence.

Patients must have sufficient fusional ability for this approach.

Medical Treatment

Medication is not routinely required for infantile nystagmus.

Drugs studied in selected older patients include:

• Gabapentin
• Memantine

Some studies suggest reduction in nystagmus intensity or improvement in visual function, but responses are variable.

Medication is generally reserved for selected symptomatic patients under specialist care.

Older therapies such as baclofen or 5-hydroxytryptophan have limited evidence.

Surgery

Surgery may be considered when there is:

• Significant abnormal head posture
• Stable eccentric null point
• Associated strabismus
• Functionally important nystagmus

Kestenbaum-Anderson Procedure

The Anderson-Kestenbaum procedure shifts the eyes so that the null point lies closer to primary gaze.

The major goal is:

Reduction of abnormal head posture

rather than complete elimination of nystagmus.

Large Rectus Recessions

Large recessions of horizontal rectus muscles have been used to reduce nystagmus amplitude in selected patients.

Results are variable.

Artificial Divergence Surgery

In patients whose nystagmus dampens significantly with convergence, surgery can create a controlled exophoric tendency so that fusional convergence is used to reduce the nystagmus.

This is reserved for carefully selected patients.

Tenotomy and Reattachment

Extraocular muscle tenotomy and reattachment has been investigated as a method of improving:

• Foveation
• Nystagmus intensity
• Visual function

It remains a specialized procedure and is not universally used.

Strabismus Surgery

Associated strabismus may be treated surgically when indicated.

Alignment can also reduce a fusion maldevelopment component in some patients.

Low-Vision Rehabilitation

Patients with significant visual impairment may benefit from:

• Magnification devices
• Electronic aids
• Preferential classroom seating
• Large-print materials
• Low-vision consultation
• Educational accommodations

Genetic Counseling

Consider genetic referral for:

• Family history of nystagmus
• Suspected FRMD7-associated disease
• Albinism
• Retinal dystrophy
• Syndromic disease

Neurology Referral

Neurologic evaluation is appropriate when there are:

• Developmental abnormalities
• Seizures
• Abnormal tone
• Regression
• Vertical or torsional nystagmus
• Opsoclonus
• Other neurologic signs

Follow-Up

Children require periodic ophthalmic evaluation to monitor:

• Visual acuity
• Refractive error
• Amblyopia
• Strabismus
• Head posture
• Underlying ocular disease
• Educational visual needs

School and Development

School performance should be monitored.

Children may have difficulty with:

• Small print
• Distance viewing
• Copying from a board
• Rapid reading
• Visual tasks under time pressure

Appropriate accommodations can significantly improve function.

Prognosis

Visual prognosis depends primarily on the underlying cause.

Isolated infantile nystagmus

Vision may be relatively good.

Sensory-deficit nystagmus

Visual prognosis depends on the underlying retinal, optic nerve, or anterior segment disorder.

Nystagmus often:

• Becomes less noticeable with age
• Persists lifelong
• Rarely disappears completely

Abnormal Head Posture

A compensatory head posture may become more apparent with age as visual demands increase.

Surgery can be helpful when the posture is:

• Large
• Persistent
• Functionally or cosmetically significant

Complications

Potential consequences include:

• Reduced visual acuity
• Amblyopia
• Strabismus
• Abnormal head posture
• Neck discomfort
• Reduced school performance
• Psychosocial impact

Oscillopsia Warning

Classic infantile nystagmus generally does not produce oscillopsia.

New oscillopsia in a patient with longstanding infantile nystagmus should prompt evaluation for:

• Acquired neurologic disease
• New vestibular dysfunction
• Change in the pre-existing ocular motor disorder

Ophthalmology Pearls

• Preferred term: infantile nystagmus syndrome rather than congenital nystagmus.
• INS usually appears during the first 6 months of life, not necessarily at birth.
• Classic INS is usually horizontal, conjugate, and reduced with convergence.
• A null point may produce a compensatory face turn, chin position, or head tilt.
• Patients with infantile nystagmus generally do not experience oscillopsia.
• Always search for a sensory cause such as albinism, foveal hypoplasia, retinal dystrophy, CSNB, optic nerve hypoplasia, cataract, or glaucoma.
• FRMD7 is an important cause of X-linked isolated infantile nystagmus.
• Fusion maldevelopment nystagmus worsens with monocular occlusion and beats toward the fixating eye.
• Spasmus nutans classically causes fine asymmetric nystagmus + head nodding + abnormal head posture and usually improves spontaneously.
• Atypical spasmus nutans, vertical nystagmus, marked asymmetry, neurologic signs, or opsoclonus should prompt neuroimaging/systemic evaluation.
• ERG is especially useful when retinal disease or congenital stationary night blindness is suspected.
• Management starts with optimal refraction, amblyopia therapy, and treatment of the underlying ocular disorder.
• Anderson-Kestenbaum surgery is primarily used to move an eccentric null point toward primary gaze and reduce an abnormal head posture.