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 Center
Professor of Ophthalmology, The University of Pittsburgh
The 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 System
Eye Movement Recordings
• Methods
 High 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.
R
Deg
L
10
Foveation Periods Within ±..5° by ±4°/sec Window
5
Deg
0
-5
0
1
2
Time (sec)
3
4
5
Eye Movement Recordings
• Value of data





Diagnosis.
Classification.
Etiology.
Therapy.
Research.
Age Distribution
30%
25%
20%
15%
10%
5%
0%
<2
<5
685 Patients 1998-2005
<10
<15
<20
Age (year)
<30
>31
Afferent System
Efferent System
Conception
Development
Birth
Infancy
Vision
Vergence, Versions
STABLE OCULAR MOTOR SYSTEM
CEMAS
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 6
May 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.
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
 Biofeedback
 Vibratory Stimulation
 Prisms, Telescopes, Contact Lenses
 Botox
 Eye Muscle Surgery
Medical Treatments
 Spectacles
 Contact Lenses
 Low Vision Aids
 Penalization (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
EYE MUSCLE SURGERY AND INS
• Simple tenotomy of all 4 horizontal recti
• Reattachment at the original insertion
• Final 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
HUMAN CLINICAL TRIALS
EYE MUSCLE SURGERY AND INS
•
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”)
Targe
t
Preferred OD Fixing Under Binocular Conditions
Targe
t
HUMAN CLINICAL TRIALS
EYE MUSCLE SURGERY AND INS
•
Improved Waveforms (Pure Jerk and Pendular to
Jerk/Pendular with foveation)
Target
Preferred OD Fixing Under Binocular Conditions
Target
HUMAN CLINICAL TRIALS
EYE MUSCLE SURGERY AND INS
•
Increased Breadth of The Null Zone
R
10
degrees
L
5 sec
R
10
degrees
5 sec
Pre-Operative
L
Post-Operative
HUMAN CLINICAL TRIALS
EYE MUSCLE SURGERY AND INS
•
1-3 Lines of Recognition Acuity Increase
LogMar Acuity
Pre-Post Tenotomy Acuity
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
LogMar OU Pre
LogMar OU Post
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 #
HUMAN CLINICAL TRIALS
EYE MUSCLE SURGERY AND INS
Improved Visual Recognition Time (Speed of Recognition)
Lo gM AR 0.94 (20/176, S ize 7)
10 00
Latency (m sec)
•
8 00
6 00
4 00
-40
-30
-20
-10
0
10
20
V e lo city (d egrees/s ec)
30
40
GAZE DEPENDENT VISUAL ACUITY
30 deg
20 deg
Fig. 1.Gaze angle
EFP
10 deg
0 deg
10 deg
20 deg
30 deg
HUMAN CLINICAL TRIALS
EYE MUSCLE SURGERY AND INS
•
Improved Gaze Dependent Visual Acuity (GDVA)
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
PREOP
POSTOP
-30
-20
-10
0
10
20
30
DEGREES OF GAZE
PRE-POST GDVA PT. 25
LogMAR Acuity
LogMAR Acuity
PRE-POST GDVA PT. 19
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
PREOP
POSTOP
-30
-20
-10
0
10
DEGREES OF GAZE
20
30
Enthesial Area
Annulus Of Zinn
“Myotendon”
CONTROL HUMAN ENTHESIS
Myelin
Nerve Ending
Axon
2u
Capillary
500u
2u
TREATMENT:ANIMAL MODEL
Etiologic
 INS with Gene Defect (RPE65 – Leber’s in Humans)
 Genetic Therapy*
Conclusions
Ask 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”