Understanding and Treatment of Infantile Nystagmus Syndrome

Richard W. Hertle, MD, FAAO, FACS, FAAP

Chief of Pediatric Ophthalmology, Children’s Hospital of Pittsburgh Director of Ocular Motility, The UPMC Eye CenterProfessor of Ophthalmology, The University of PittsburghThe Laboratory of Visual and Ocular Motor Neurophysiology

Examination Techniques: Highlights• Acuity

Binocular and Monocular Gaze-Dependent

• Color, Contrast

• Ocular Motor Strabismus Nystagmus – “nulls” Head Posture

• Accommodation

• Refraction Objective

Visual Acuity Testing

20/400 20/200 20/100 20/50 20/25

Evaluation Techniques: Afferent System

• Vision testing procedures Behavioral Vision Testing (acuity, color, stereo) Visual Evoked Responses (flash, pattern, sweep) Electroretinography (flash, pattern) Contrast, Color and Visual Field Testing

Evaluation: Efferent SystemEye Movement Recordings

• MethodsHigh speed photographic methods.“Contact” electrooculography. Infrared reflectance oculography.Scleral contact lens/magnetic search coils.

Eye Movement Recordings

• Diagnosis/Differentiation of Eye Movement Disorders.

• Utility as an “Outcome Measure” in Clinical Research.

0 1 2 3 4 5-5

0

5

10Foveation Periods Within ±..5° by ±4°/sec Window

Time (sec)

R

L

Deg

Deg

0%

5%

10%

15%

20%

25%

30%

<2 <5 <10 <15 <20 <30 >31

Age (year)

Age Distribution

Eye Movement Recordings• Value of data

Diagnosis. Classification. Etiology. Therapy. Research.

685 Patients 1998-2005

Afferent System Efferent System

Conception

Birth

Infancy

Development

STABLE OCULAR MOTOR SYSTEM

Vision Vergence, Versions

Disease Name INFANTILE NYSTAGMUS SYNDROME (INS) [Old Congenital Nystagmus and “Motor and Sensory” Nystagmus]

Criteria Infantile onset, ocular motor recordings show diagnostic (accelerating) slow phases

Common Associated Findings

Conjugate, horizontal-torsional, increases with fixation attempt, progression from pendular to jerk, family history often positive, constant, conjugate, with or without associated sensory system deficits (e.g., albinism, achromatopsia), associated strabismus or refractive error, decreases with convergence, null and neutral zones present, associated head posture or head shaking, may exhibit a ”latent” component, “reversal” with OKN stimulus or (a)periodicity to the oscillation. Candidates on Chromosome X and 6May decrease with induced convergence, increased fusion, extraocular muscle surgery, contact lenses and sedation.

General Comments Waveforms may change in early infancy, head posture usually evident by 4 years of age. Vision prognosis dependent on integrity of sensory system.

CEMAS

Nystagmus and Vision• “Sensory” System

Refractive Error Amblyopia Abnormal Binocular Vision Ocular Media Damage Retinal Disease Nycloptia/Photophobia Optic Nerve Disease Visual Cortex Disease

• “Motor” System Oscillation Strabismus Abnormal Pursuit (tracking) Abnormal Saccades (fast eye

movements)

“MOTOR” SYSTEM TREATMENT

Medications Visual Training (strabismus, binocular dysfunction)Acupuncture BiofeedbackVibratory StimulationPrisms, Telescopes, Contact LensesBotoxEye Muscle Surgery

Medical Treatments

SpectaclesContact LensesLow Vision AidsPenalization (patching, drops)

Medical Treatments Photophobia Nystagmus

• Sedatives, Hypnotics, Neuroleptics, Anti-seizure drugs

• Acupuncture, Biofeedback, Vibratory Stimulation Strabismus and binocular dysfunction

• Orthoptics

• Spectacles

• Penalization

“Nystagmus” Surgery• Effect a Positive Change on the Oscillation

Improve Waveform Increase Foveation Broaden Null Position Improve Periodicity

• Treat Anomalous Head Positions

ANIMAL MODEL OF INS

• Achiasmatic Belgian Sheepdogs

• Ocular Motor Behavior

• Ocular Motor Analysis

• Infrared Oculography Recording

• Preoperative and Postoperative Visual Behavior Eye Movement Recordings

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

• Simple tenotomy of all 4 horizontal rectiSimple tenotomy of all 4 horizontal recti• Reattachment at the original insertionReattachment at the original insertion• Final Effect related to underlying visual system diseaseFinal Effect related to underlying visual system disease

Hertle RW, Dell’Osso LF, FitzGibbon, EJ, Yang D, Mellow SD. Horizontal Rectus Muscle Tenotomy In Children with Infantile Nystagmus Syndrome: A Pilot Study. Journal of AAPOS 2004:8;539-548

Hertle RW, Dell’Osso LF, FitzGibbon, EJ, Thompson DJS, Yang D, Mellow S. Horizontal Rectus Tenotomy In Patients with Congenital Nystagmus: Results In Ten Adults Ophthalmology 2003:11;2097-2115

• Increased Foveation (amount of time during a beat of INS during which the eye is moving at <4 deg/sec and within a few degrees of the target – when the eye/brain “sees”)

Target

Target

Preferred OD Fixing Under Binocular Conditions

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

• Improved Waveforms (Pure Jerk and Pendular to Jerk/Pendular with foveation)

Target

Target

Preferred OD Fixing Under Binocular Conditions

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

Post-Operative

5 sec

R

10 degrees

L

R

L

10 degrees

5 sec

Pre-Operative

• Increased Breadth of The Null Zone

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

• 1-3 Lines of Recognition Acuity Increase

Pre-Post Tenotomy Acuity

0

0.10.2

0.30.4

0.5

0.60.7

0.80.9

1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Patient #

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gM

ar

Ac

uit

y

LogMar OU Pre

LogMar OU Post

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

• Improved Visual Recognition Time (Speed of Recognition)

400

600

800

1000

-40 -30 -20 -10 0 10 20 30 40

LogMAR 0.94 (20/176, Size 7)

Lat

en

cy

(ms

ec)

Velocity (degrees/sec)

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

GAZE DEPENDENT VISUAL ACUITYGAZE DEPENDENT VISUAL ACUITY

30 deg 20 deg 10 deg 0 deg 30 deg20 deg10 deg

Fig. 1.Gaze angle

E F P

• Improved Gaze Dependent Visual Acuity (GDVA)PRE-POST GDVA PT. 19

00.10.20.30.40.50.60.70.80.9

1

-30 -20 -10 0 10 20 30

DEGREES OF GAZE

Lo

gM

AR

Acu

ity

PREOP

POSTOP

PRE-POST GDVA PT. 25

00.10.20.30.40.50.60.70.80.9

1

-30 -20 -10 0 10 20 30

DEGREES OF GAZE

Lo

gM

AR

Acu

ity

PREOP

POSTOP

HUMAN CLINICAL TRIALS HUMAN CLINICAL TRIALS EYE MUSCLE SURGERY AND INSEYE MUSCLE SURGERY AND INS

“Myotendon”Annulus Of Zinn

Enthesial Area

CONTROL HUMAN ENTHESIS

Axon

Myelin

2u

2u

500u

Nerve Ending

Capillary

TREATMENT:ANIMAL MODEL

Etiologic INS with Gene Defect (RPE65 – Leber’s in Humans)Genetic Therapy*

ConclusionsAsk For:

• Accurate Evaluation Afferent System Efferent System

• Accurate Diagnosis Sensory System Deficits Nystagmus Type Strabismus Head Posturing

• Medical Treatment Options• Surgical Treatment Options• Treatment versus “CURE”