Idiopathic infantile nystagmus: Diagnosis and treatment

Idiopathic Infantile Nystagmus: Diagnosis and Treatment Robert D. Reinecke, MD Current concepts of idiopathic infantile nystagmus are summarized, with special attention to treatment and differential diagnosis of this condition. Advantages of the Anderson procedure over the Kestenbaum procedure are suggested for head turn associated with this condition, and the need for further studies is acknowledged. The importance of the extended slow phase in understanding the waveforms of infantile nystagmus is stressed. Our studies reinforce What I believe to be the natural history of infantile nystagmus, as well as the history of periodic alternating nystagmus. The critical delineation of diagnosing periodic alternating nystagmus is emphasized with respect to the type of operation to avoid overcorrection of head turns in patients with nystagmus. Continued searches for manifest latent nystagmus are important, because that condition is currently the only truly treatable nystagmus. I thankthe American Association for Pediatric Ophthalmology and Strabismus forthe privilege and honor of presenting the 1997 Costenbader Lecture. (J AAPOS 1997;1:67-82)

i

thank David Guyton for his generous introduction. Further thanks go to those mentors and peers who kindled my interest in nystagmus and contributed to the material discussed here. Of special note was David G. Cogan, who suggested during my medical school days that I join him in his fascination with optokinetic nystagmus (OKN)? Kurt Simmons enhanced my interest in nystagmus through his devotion to early screening of children as he completed his doctorate in our laboratory and as we toyed with OI~2q as a screening modality. Many fellows, residents, and medical students have helped assemble the jigsaw puzzle of nystagmus as I see it today. The missing pieces are lessening. To all my coworkers, I extend my deep gratitude. I am grateful to the nominating committee, the Costenbader Society, and the American Association for Pediatric Ophthalmology and Strabismus for allowing me the joy and honor of presenting this lecture in Costenbader's memory. Would Costenbader enjoy my presentation? I am unsure, because nystagmus is conspicuously absent in his writings2-42; it is not even mentioned as a factor in his articles on prognoses

From the Foerderer Eye Movement Center for Children, I~ills Eye Hospital, Departmere of Ophthalmology, Jefferson Medical College of Thomas Jefferson University, Philadelphia. Presented as the 1997 Costenbader Lecture at the annual meeting of the American Association of Pediatric Ophthalmology and Strabismus, Charleston, South Carolina, April 2-6, 199Z Reprint requests: Robert D. Reinecke, MD, Foerderer Eye Movement Center for Children, Wills Eye Hospital, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 1910Z Copyright © 1997 by the American Associationfor Pediatric Ophthalmology and Strabigmus. 1091-8531/9755.00+0 75/1/82120

Journal of AAPOS

for strabismus 6,is and amblyopia? ° As evidenced by his two articles on accommodometers, 14,19 however, he may have been intrigued by gadgets, and several are mentioned in my presentation. This talk honoring Costenbader's life and contributions gives me an opportunity to mimic his format as he gave presentations of current treatments of pediatric ophthalmic subjects. I will attempt to bring together some scattered facts and my opinions into a vignette of infantile nystagmus. As we review the subject matter of Costenbader's publications, the chronology and variety of his interests are impressive. He was a renaissance man. Note the subjects and the impressive coauthors of his publications? -42 TERMINOLOGY

AND DEFINITION

Costenbader favored the term infantile esotropia, as opposed to congenitalesotropia,for esotropia appearing in the first year of life but seldom present at birth. 28The onset of nystagmus has many of the same chronologic features of infantile versus congenital, and my preferred term for nystagmus appearing in the first year of life is therefore infantile nystagmus, as opposed to congenital nystagmus. Infantile nystagmus is seldom present at birth, except in the case of the unusual dualjerk congenital nystagmus. Adding the term idiopathic for nystagmus not associated with any discoverable defect on the sensory side of vision also seems appropriate. Two problems, albinism and esotropia, are noteworthy in their common association with a condition that seems indistinguishable from infantile idiopathic nystagmus. Idiopathic infantile nystagmus (also called motor nystagmus or congenital nystagmus) is best described as a jerk

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Gaze right

gF o v e a t i o n4[

A A: os/-

.

veo,,on

decrement in the vision of the patient with latent nystagmus than in a subject with idiopathic-infantile nystagmus. Conversely, if manifest latent nystagmus can be made latent, a remarkable improvement in the patient's vision is found. 4s Null Point

1

3econd

1 second

FIR. 1. Diagram of horizontal eye movements in idiopathic infantile nystagmus as gaze is shifted from right to left. Note the foveation of each eye, the changing direction of the foveation of each eye, and the reversed direction of the fast and slow phases with the change of gaze direction.

nystagmus with increasing velocity of the slow phase of the waveform. The term nystagmus is derived from a term for head nodding as sleep is approached, with the accompanying slow drift of the head punctuated with the quick head jerk back to attention. Dell'Osso and Daroff 43 deserve credit for calling our attention to the slow-phase characteristics of idiopathic infantile nystagmus. More evidence is accumulating that the slow phase is the problem. The fast phase is a normal saccade and fulfills the criteria for a usual saccade. The amplitude of idiopathic infantile nystagmus decreases as the null point is approached. The slow phase draws the eye toward the null point or points. The further from the null point, the greater the action of the slow phase to draw the eye away from the target, and thus the greater the amplitude of the saccade, or quick phase, needed to move the visual axes back to the target. Another way of stating the same thing is this: as fixation nears the orbital coordinates of the null point in idiopathic infantile nystagmus, foveation time typically increases. Foveation Times Foveation time is the term used for the interval where the

eyes' velocities are less than 5 degrees/sec. 44Movement of the eyes at speeds faster than 4 to 5 degrees/sec interferes with foveal vision. On recordings of eye movements, the tracing is level or almost level during the brief foveation periods of idiopathic infantile nystagmus (Figure 1). Interestingly, the foveation period in idiopathic infantile nystagmus occurs just as the fovea is drawn back to the object of regard with the quick phase. Thus, as the saccade finishes, the fovea is on target and can remain there during the foveation period. Contrast this with the latent nystagmus slow phase, in which the velocity decreases to allow the eye to remain still just before making a fast movement to move the fovea back on target, a most inefficient method of seeing (with the eye quiet when the fovea is off rather than on target; Figure 2). This helps explain the large decrement in vision when latent nystagmus becomes manifest. Anystagmus of the same velocity and amplitude causes a much greater

The null point makes idiopathic infantile nystagmus much like physiologic end-point nystagmus, which many of us exhibit. Physiologic end-point nystagmus could be characterized as idiopathic infantile nystagrnus with a wide null point, 46 extending over most of our gaze with jerk nystagmus appearing as we approach the limits of adduction or abducfon. One might think of idiopathic infantile nystagrnus as a normal physiologic end-point nystagmus, but with a substituted small null point with nystagmus increasing in amplitude as the eyes are drawn to a distant null point by the slow phase. Consistent with end-point nystagrnus, the jerk in idiopathic infantile nystagmus is in the direction of the attempted gaze away from tile null point. In both physiologic end-point nystagmus and idiopathic infantile nystagmus, the eyes seldom overshoot the foveae as the nystagmus jerks the fovea to the target. When the gaze is on the other side of the null point, the nystagrnus reverses direction, jerldng the fovea back to the target of regard but seldom past it. We have documented and studied these fixation characteristics with movies of patients' macular areas with a target's shadow on the fundus photograph of a scanning laser camera. The null point is more aptly called the null zone. The fovea is jerked toward the target, but if the gaze is not in the null zone, the slow phase draws the fovea toward the null zone. When the gaze is in the null zone, the slow phase often drags the eye first in one direction and then in the other, giving rise to dual-jerk nystagmus (Figure 3). Occasionally, we see small pendular eye movements instead of a fine dual jerk at the null point. These may be interpreted either as persistent phase II waveforms from the development of idiopathic infantile nystagmus or as the C 2 waveforms to which Goldstein refers in his description of extended slow phases. 47Perhaps the pendular movements in the null zone are the same; that is, the C 2 waveform and phase II of the developing idiopathic infantile nystagmus are equivalent. The pendular waveforms often seen at the null point are depicted in Figure 4. NATURAL HISTORY OF IDIOPATHIC INFANTILE NYSTAGMUS Most infants with idiopathic infantile nystagmus have little or no visible nystagmus for the first 2 or 3 months of life. Then wide, horizontal, symmetric swings of the eyes are noted easily. In a unique case report, Irene Gottlob, 48 formerly of our laboratory and now in Switzerland, recorded eye movements of a 5-week infant who was thought to be normal but in whom idiopathic infantile nystagmus subsequently developed. During the first 6 weeks of fife, the infant had

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H a n i f e s t Latent N y s t a g m u s

N

ull --

-~U L

L k

D

Left Left

R

L

4

L

)

LA.AAJ Gaze l e f t Ideopathic Infantile Nystagmus FIB. 2. Note the contrasting waveform of infantile nystagmus (lower tracings) compared with latent and manifest latent nystagmus (upper tracings). In the latter, the foveation plateau is off the fovea and thus serves no useful function for the patient. Conversely, the foveation or plateauing of the slow phase in idiopathic infantile nystagrnus occurs at the termination of the fast phase, which brings the fovea on target and thus facilitates vision. Heavy arrow indicates the slow phase direction.

square-wave jerks as saccadic responses were developing and used them for pursuit. No nystagmus was seen. Triangular or phase I infantile nystagmus then developed, eventually resulting in typical idiopathic infantile nystagmus. The wide, horizontal, swinging eye movements called phase I are easily noted and are often misinterpreted as blindness at 2 to 4 months of age. The term triangMar eye movements is used to describe these because of their wide amplitude and low frequency--typically 0.75 to 1 Hz with an amplitude of about 45 to 60 degrees. Recordings of these large eye movements appear like pyramids or partial triangles, hence the term. With the triangular eye movements of phase I, the child exhibits almost no control of horizontal pursuit eye movements and no purposeful horizontal saccades. If one attracts the child from below or above, however, the child's normal vertical pursuit and saccadic eye movements can be demonswated. Intact vertical eye movements are often demonstrated most easily with vertical O K N stimuli. Also noteworthy is the infant's unexplained smile that frequently accompanies these vertical O K N stimuli and responses. The vertical O K N responses are of importance, because

the parents and the referring pediatrician are often concerned that the child may be blind on noting the lack of horizontal voluntary fixations. Demonstration of the O K N response to the parents reassures them that vision is present. The progression ofwaveforms is shown in Figure 5 but is more dramatically appreciated in television tapes. Recently, I used the technique of Monte Stavis, a former fellow with me, who asks parents to aim a home video camera just over the top of the family television set to document the status of nystagmus of the child viewing the television (Stavis M, personal communication, 1996). We have been able to record the evolving waveforms in consecutive eye movement recordings and television tapes on multiple children. My first clue of this progression from the wide, swinging, triangular movements to finer nystagmus was provided by a grandmother in the presence of her daughter and granddaughter. The family had dominant idiopathic infantile nystagmus.49 They had brought the baby for examination at 4 weeks of age to seek my opinion on whether the child had

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Gaze r i g h t

Age

~~~Foveation

Foveation

I

II

3-6 mos

6-24 mos

Nul]I zone

Gaze 0 ~

~ ~ * t" Feveation

-I-

~ Gaze l e f t

Right

Foveation

I ~ d. 'dPLeft

"drLeft 1 second

4" 1` Foveation 1 second

I second

1 second

FIG. 3. Diagram of horizontal eye movements as gaze is shifted from right to center (the null zone) and to the left. At the null zone, note the small fine jerks to the left and right and the extended foveation.

Gaze

III 24-36 mos

right

Foveation

Null zone

Foveation

Null zone

~veationt

-

-

Gaze l e f t

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) 1 second

) 1 s~©ond

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FIG. 4. Diagram of horizontal eye movements as gaze is shifted from right to center (the null zone) and to the left. At the null zone, note the extended slow phases of the C2variety, which are pendular.

nystagmus. I was about to say, "I don't see any nystagmus," when the grandmother admonished me, "Take your time and try to be certain in your diagnosis. I have been through this with many of my children and grandchildren. The doctor often has thought them to be blind, only for them to see fine as they aged. Other doctors have told us that one of our children had no nystagmus, only later to see obvious nystagmus." I took her seriously, but it was to be almost a decade before we had accumulated sufficient longitudinal studies to chronicle the changes discussed here that were reported from our laboratory by Reinecke, Guo, and Goldstein. s° Occasionally, the patient with phase I nystagmus will be taken to a neurologist, who interprets phase I as indicative of a seizure disorder--even to the point of ordering 24-hour television monitoring in the hospital. (There is epileptic nystagmus, but that entity shows asymmetric jerks and evidences no slow phases.) The large triangular eye movements we describe as phase I of idiopathic infantile nystagxnus should not be confused with the oculogyric crises exhibited by patients with Arnold-Chiari malformation as they suffer in-

)

FIG. 5. The three phases of idiopathic infantile nystagmus evolution are diagramed with the usual appearance times of the waveforms dominant for that age. Note the small flat area appearing close to the point of reversal or apex of phase I.

termittent pressure on the midbrain and vermis of the cerebellum and have the wild intermittent chaotic asymmetric eye movements often classed as epileptic nystagmus. Eye movement recordings will show the difference between epileptic and phase I of idiopathic infantile nystagmus. The large horizontal triangular waveforms just described can be considered as phase I in the development of idiopathic infantile nystagmus. At about 6 to 8 months of age, phase II develops. Phase II is characterized by symmetric, lowamplitude, pendular nystagmus of 3 degrees or so at about 6 Hz. As the child acquires phase II nystagmus, parents may interpret this as a significant improvement of the child's eye movements and often hope for complete resolution of the problem. The triangular waveforms give way to more and more pendular waveforms, but careful analysis of idiopathic infantile nystagmus recordings of adults shows an occasional persistent triangular waveform and many pendular phase II waveforms. An occasional patient will have the pendular phase ]I remain constant throughout his or her life and never proceed to phase 111.Phase 111,which develops at about 18 to 24 months of age, consists of jerk and slowwaveforms and the development of a null point. The slow component of the phase III waveform shows the typical increasing velocity. Occasionally, a recording can catch all three phases sequentially (Figure 6) in one session, demonstrating the triangular, pendular, and jerk forms that we designate as phases I, II, and HI. With the genesis of a null zone, a preferred head turn may appear if the null zone is not straight ahead. Considerable variation is seen with respect to the onset of phase lB. Illustrative of this point is the nystagmus phase progression of identical twins. A proven nuclear identical twin set I observed had similar landmark developments, but the onset of phase III in one twin was 4 months ahead of that in the other. A compensatory head nodding develops in some subjects. The onset of the head nodding mayvary from age 2 to 24 years. No explanations are offered for the widely variable onset of head nodding,which is not to be confused with the head nodding of spasmus nutans, an asymmetric nystagmus.

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Horizontal Target

'1-o.o3

o

-0.03

O

Phase I

0.00

Phase II

©

Phase

-o.o5

Ill

3.35

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Time in milliseconds '

t ~ 1200

I ~ 2400

I ' 3600

i ' 4800

I ' 6000

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1 ' 8400

I i 9600

I ' I 108092000

FIG. 6. Horizontal eye movement recording of a 5-year-old demonstrates the three phases occurring sequentially at a time when the majority of the waveforms are jerk with increasing velocity of the slow phase. LE, Left eye; RE, right eye.

E X T E N D E D SLOW PHASES The natural history of the three phases of infantile nystagmus has been described. Now let us examine how the three phases can be teased apart with respect to phase III waveforms. For that, we turn to new information developed by Hershel Goldstein, my colleague in our laboratory. Changes in nystagmus waveforms and intensity of nystagmus are dependent on the position of gaze with respect to subjects' orbital coordinates. However, the waveform in any one position with respect to constant orbital coordinates, identical vergence, visual acuity demands, and level of vigilance (or distraction) is remarkably constant, like the fingerprint ofvergence. Idiopathic infantile nystagmus is generally constant within the parameters just described, except for sleeping, but varies with attention, often worsening as the subject strives to see better. Daydreaming might therefore be expected to make nystagmus less. One father and daughter, both of whom have idiopathic infantile nystagmus, remarked that their nystagmus stopped when they were distracted and performing mental arithmetic. When they did serial subtractions of sevens during eye movement recordings, we documented halting of their nystagmus. Several years elapsed before we understood what was happening. Goldstein and Gottlob sl and Goldstein alone 47found that such patients, and in fact most if not all patients with idiopathic infantile nystagmus, can be mentally distracted, and the fast phase can be delayed so that extended slow phases can be seen. These extended slow phases with two or more components seem to be constant for any one patient.

When the patient with idiopathic infantile nystagmus has the target abolished, the quick phase of the nystagrnus remains. Because no target is present, however, the quick phase loses its precision and the waveforms become less nearly identical. If we add to the darkness a distracting mental task, we can eliminate the quick component and reveal the extended slow phase. Eye movement recordings shown in Figure 7 depict these three states. In the visual state, the usual jerk nystagmus with increasing velocities of the slow phases is seen. When darkness ensues and no visual target is visible, the quick phases become somewhat random. With the third stage of mental distraction, the extended slow phase is seen. When visual attention is lost, the eyes start a movement in the direction of the slow phase. If the eyes are in a position distant from the null zone, this phase may then be prolonged to the right or left and eventually, in 200 msec or so, start to plateau. Goldstein called that phase C1.47 We believe that it may represent evolutionary phase I (described previously) that is linked to the right and to the left during phase I. Either during the slow phase, after it, or independent of it, pendular movements of the eye are evidenced. They mimic the pendular nystagmus seen in phase II of the infantile development of the nystagmus and were called C2 by Goldstein. 47 The patient may interrupt these extended slow phases at any time with the fast phase as visual attention returns. Repeated studies with attempts at distraction are necessary to bring out both of the components of the extended slow phase (Figxtres 8 through 10). Goldstein 47 points out that these similarities of waveforms and their analyses are much easier to visualize in velocity

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~

USUAL NYSTAGMUS VISION ENGAGED

.

1 SEC

NO VISUAL TARGET EXTENDED SLOW PHASE VISION NEUTRAL VISION DISENGAGED

FIG. 7. Horizontal eye movement recording of a patient while in the testing paradigm. First recording documents the typical jerk nystagmus; next, the visual targets are eliminated and the precision of the jerk is lessened. Finally, the vision is disengagedby requiring mental judgment and choices unrelated to vision, with the appearance of the extended slow phase.

i,

Cl

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os

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Right 5 deg Left I

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! second

I second

FIG. 8. The C~extended slow phase is diagramed. As the attention of the subject is changed to mental calculations (inattention), the subject's eyes drift with the extended slow phase. The jerk, or quick phase, will be immediately resumed on visual attention.

CI

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I

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FIG.9. Diagram of subject with idiopathic infantile nystagmus who has been given the task of subtracting serial sevens. Note the slew, large waveform of C1, contrasted with the lower amplitude, higher frequency C~. In this example, visual attention would cause resumption of the idiopathic infantile nystagmus with the jerking to the right.

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OD

iiiiiiiiiiiii!Inatt

'

iiiiiiiiiJiljlilililiiii

os

I

Right 5 deo Left i

1 second

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FIG. 10. Occasionally, an extended pendular slow phase (C2) becomes evident when attention is changed from visual to mental. This is diagramed as we have found it and is remarkably similar to the pendular or evolutionary phase II of idiopathic infantile nystagmus.

recordings than in position recordings. Such an analysis is demonstrated in the actual recordings and analyses shown in Figure 11. The interruption of an extended slow phase (CI) with a jerk resets the start of the slow phase. Most patients continually interrupt their extended slow phase at the same place with each cycle for each set of orbital coordinates when other parameters are constant. More work is required, but it appears that the timing of the interruption of the slow phases and the combination of the two waveforms, C 1 and C2, determine the phase III waveform. This may explain the progression from phases I through III in the childhood evolution. A patient seems to have the same combination of extended slow waves in all directions of gaze, but the interruptions of the basic extended slow waves that are a combination of C, and C 2determine the exact waveform for each set of orbital gaze coordinates. The combination of the two waveforms with variable onset gives a large array of waveforms, ample to explain the waveforms in any one subject. These findings make the vigilance factor dominant as we try to assess various treatments for nystagrnus. We have yet to perform the same studies with torsional and vertical idiopathic infantile nystagmus. Latent and manifest latent nystagmus can be shown to exhibit the same C 1 and C 2 waveforms in the extended slow phase. Mentally distracting the patient after occluding an eye brings out the extended slow phase with minimal vergence change. Covering the right eye allows the nystagmus to become manifest: mental distraction then allows C 1 to drag the eyes symmetrically to the right without the quick phase of recovery. The curves suggest a background pendular waveform of C a contributing to the curve. When the left eye is covered and the patient is distracted, the extended slow phase moves the eyes in an opposite direction, toward the nose with respect to the open eye. This curve seems to be almost a pure C1. HEAD POSITION

MEASUREMENTS

Preferred head position measurements associated with null points are technically easy to document precise b, and

LE V I E W I N G V !

---

"

LE

RE VIEWING -2.3D E G V

LE

0

RE

FIG. 11. Latent nystagmus recording showing the extended slow phase which can be broughtout with either eye fixingand the subject mentally distracted. Channel labeled V is vergence. Channels labeled RE and LE show horizontal eye positions of right and left eyes. Covering the left eye brings out an almost pure C1; occluding the right eye with distraction brings out C1 and the pendular component of C2 as well.

repeatedly if eye and head movement recordings are done, but are awkward and imprecise in the examining room. An instrument we developed recently seems to overcome these difficulties (Figure 12). A small laser pointer is attached to a head mount. (An indirect ophthalmoscope will work if you

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\

/

Oo

tRight 1 5 deg ~lbLeft

Target 0 °.

\ FIG. 12. Diagram of head-mounted laser pointer in use while the patient is reading down the chart to the smallest visible print. A small paper adhesive dot is pasted on the wall to allow calculation of the degree of head turn.

attach the laser pointer to it.) The straight-ahead position of the laser pointer is set by alignment of the pointer beam to the tip of the subject's nose. The pointer is mounted in a manner such that it can be moved about the coronal axis. The anatomic vertical habitual straight head position is measured with a gravity-based deviometer placed on the nose tip and glabella. The horizontal alignment of the pointer is done by moving the pointer level and setting it with the same gravity-based deviometer. The patient is asked to read the acuity chart to his or her best acuity line while wearing the head-mounted laser. The laser pointer is aimed ahead or behind the patient. The beam is seen on the forward or back wall of the examining room, and its position is marked on the wall with a small peel-offdot. The dot's position in relation to the straight-ahead position is easily measured, and the angle of the head turn is calculated with the tangent function. (This gadget will be reported on in detail by Basil Pakeman, a current fellow with us.) We have found the system reproducible and easy to use. Patients are fascinated by it. If the preferred head position is straight ahead, the red laser beam will be precisely ahead or behind the patient. We often aim it behind the subject because of some subjects' fascination with the laser beam if it is on the front ,wall. DUAL-JERK NYSTAGMUS: A CONGENITAL NYSTAGMUS I have seen only one form of idiopathic infantile nystagmus documented at birth. This form, dual-jerk nystagmus, seems to remain constant for the subject's life. Occasionally, a patient's idiopathic infantile nystagmus will evolve into dualjerk nystagmus, but more commonly the dual-jerk nystagmus is of small amplitude at birth and is easily overlooked throughout the first 2 years and beyond. Good vision can be predicted. The amplitude is usually less than 3 degrees and the frequencyis about 0.5 Hz. The waveform is seen as small jerks alternating right and left, with good foveation periods as depicted in Figure 13. An apparent dual jerk is seen in otherwise typical idiopathic infantile nystagmus with a foveation period

1 second

O°

FIG. 13. Dual-jerk nystagmus. The small amplitude slow waves pull the eye slightly off target alternatelyta the right and left, with the ensuing small jerks rapidly bringingthe eyes' foveae to align on the target.

halfway down the slow phase, as depicted in Figure 14. This gives the appearanceof a dual jerk, because there is a halt in the slow phase. In actuality, however, this is not dual jerk but back-to-back interrupted slow phases, with the foveation followed by the remainder of the slow phase and then the jerk. As with some other features of nystagmus, clinical observation misses a good bit of the detail of such eyes' movements.

IDIOPATHIC TORSIONAL INFANTILE NYSTAGMUS Idiopathic infantile nystagmus may be other than horizontal. The second most common form of idiopathic infantile nystagmus after horizontal is torsional. The ease of detection of torsional nystagmus is dependent on where the pivot is for the torsion arm. For example, if the center of rotation of the torsion is in the center of each pupil and on visual axes having a zero angle •, no horizontal or vertical movements of the eye will be seen despite steadily beating torsional nystagmus. However, such nystagmus can be seen ophthalmoscopically when viewing the disc, because the disc is eccentric from the torsion axis of the fovea and will be seen to move. Indeed, if the usual horizontal and vertical eye movement recordings are done on the pupilcentered torsional nystagmus, no nystagmus will be seen on the tracing. If the iris is carefully viewed with a slit lamp, however, the torsional nystagmus is apparent. Because this variety of nystagmus is seldom detected grossly, only special circumstances bring it to our attention. The most common time for it to be seen is after an operation for another eye condition, when the ophthalmologist views the torting iris with a slit lamp. Often this first observance of the torsional nystagmus starts an unproductive search for a cause. Torsional eye movement recordings done with a special torsional eye coil can document the nystagmus. In such recordings, the waveforms of the slow and jerk phases are similar to those of horizontal idiopathic infantile nystagmus, with increasing velocities of the slow component. Little can be said about the early development of this form of idiopathic infantile nystagmus, because we usually see it late and have had no opportunity to see it in the young child. I suspect that there may be some varieties

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75

G a z e right Foveation

/-"~...~ /-~.~ / ~

OD

Gaze left

.rRig,t

15 de9 '~Left I second

Foveati on 1 second

FIG. 14. Pseudo-dual-jerk nystagmus is diagramed. Note the foveation about halfway down the slow phase. In this case, the jerk portion .overshoots the fovea, in contrast to the usual jerk, which snaps the fovea to the object of regard.

of this form with phases I and II, but we have yet to document even one. TORSIONAL WINDSHIELD NYSTAGMUS

WASHER

While Hayashi was in our lab, we documented latent nystagmus (as it becomes manifest) blocking torsional nystagmus, implying a hierarchic order to nystagmus types (Hayashi T, Reinecke RD, unpublished data, 1995). More commonly, when a patient has more than one type of nystagmus the patient will spontaneously switch from one to another. Periodic alternating nystagmus is notorious for embedding itself in idiopathic infantile nystagmus associated with albinism. Torsional idiopathic infantile nystagmus and horizontal idiopathic infantile nystagmus may be combined with some unusual waveforms. It is easy to confuse different forms of nystagmus if all the alternative forms of idiopathic infantile nystagmus are not considered. One of the easiest forms of idiopathic infantile nystagmus to detect grossly is the torsional type where the pivot of the torsion is other than the visual axis, thus giving a combination of horizontal and torsional nystagmus. If the pivot of the torsional idiopathic infantile nystagmus is not in the center of the pupil but rather, for example, on the left cheek of the subject, the nystagmus is obvious. By recording the x and y parameters of such nystagmus and reconstructing a two-dimensional graph, we can demonstrate the torsional path. Bedell and White s2aptly named this windshield wiper nystagmus because the arc of the eye movements can be described best by noting where the pivot of the windshield wiper is located. The pivot may be on the forehead, cheek, or temple (Figure 15). Because the pivot of the nystagmus maybe such that the lever arm of the torsion of one eye differs from the other, some moderate asymmetries in the horizontal and vertical parameters are often seen. However, if the pivot of the windshield wiper is estimated, then the asymmetry can be easily noted. Caution is urged regarding the depth ofworkup for such patients. I have not seen pathology cause torsional nystagmus in those without oscillopsia, vertigo, or cerebellar symptoms. If you suspect seesaw nystagmus or other directional or phase asymmetry

FIG. 15. Idiopathic infantile torsional nystagmus. A, Pure torsional with no vertical or horizontal eye movements. B, Pivot on the left cheek and the resultant almost oblique movements of the eyes, which are actually moving in an arc. C, Pivot of the windshield wiper on the left temple and the resultant arc of movements of the two eyes, with the disparity of eye movements caused by the different radii of the

wipers. of nystagmus, however, then look carefully for such nystagmus to be spasmus nutans in a child (with the usual caution about chiasmal gliomas) or midbrain pathology in an adult. A curious documentation of the type of nystagmus that the patient exhibits can be invoked by the use of the windshield wiper concept of the extended lever or pendulum. For example, if the point of the windshield wiper pivot is exactly between the eyes on the glabella, then the nystagmus would be seesaw. If one has lever arms pivoted at infinity straight ahead, then pure horizontal or vertical nystagmus would be generated, depending on the plane of the pendulum. If the pivot arm is at infinity to the right or left, then retraction or vertical nystagmus would be generated, again depending on the plane of rotation. VERTICAL IDIOPATHIC NYSTAGMUS

INFANTILE

Although this is uncommon, idiopathic infantile nystagmus is occasionallyvertical. Chaudhry and coworkers 53recently described such a ,case, noting that theirs was the first such report. Perhaps it was, but it was certainly not the first observed case; vertical idiopathic infantile nystagmus is not that rare and is not uncommonly autosomal dominant. The

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vertical variety goes through the same I, II, and III phases as does the horizontal, with chin-up or chin-down head positions developing, depending on the vertical null zone of the patient. SPATIAL ORIENTATION Spatial orientation of patients with nystagmus has in the past been intuitively thought of by researchers as abnormal. The ability of a patient with idiopathic infantile nystagmus to perform complex visual tasks, sometimes even better than most, may astound us. Lou Dell'Osso, a productive nystagmus researcher who himself has idiopathic infantile nystagmus, pointed out in a publication with coworkers s4 that one of the more complex visual tasks is skeet shooting or bird hunting, which he does With trophy results. One subject I have followed up for years is a national pistol shot expert; another teaches evasive driving to law officers. With these accounts, it is not surprising that carefully devised experiments, done by Hershel Goldstein in our laboratory and reported by Goldstein, Gottlob, and Fendick, 5s demonstrated that the subject is aware of the spatial location of objects over the entire visual field throughout the nystagmus waveforms. This is contrary to the sensory picture I once taught, which maintained that subjects with idiopathic infantile nystagmus had a stroboscopic vision with perception of detail only during foveation or during reversal of eye movements when velocities of the eyes were zero. In retrospect, it was silly teaching on my part. Those of us with normal visual patterns have constant eye movements, yet we see everywhere, all the time, excepting some reduced thresholds during saccadic suppression. The duration of the saccades in idiopathic infantile nystagmus is brief, and any saccadic suppression does not seem to interfere with the continued perception of space in all directions. The patient with idiopathic infantile nystagmus spends the great majority of the time in the slow phases, only slightly slower than the speed of normal vergences. SURGICAL TREATMENT Because the C 1 resembles to a modest extent the vergence speeds, we can suggest that such surgical procedures as the Kestenbaum or Anderson operations may have as their primary result an alteration of the slow phase. The fast phase should be considered only a saccadic response. If that is the case, the resections and recessions should have a somewhat similar effect on head turns of nystagmus as when they are done asymmetrically for patients with strabismus. We are in the midst of a clinical study to see whether the resections (the Kestenbaum procedure) are needed when one does only the recessions (the Anderson procedure). Recently, one of our clinical investigators on this issue noted the marked quietness of the eyes with the Anderson procedure and the great results with only the recessions. I suspect that now we will be hard pressed to get him to do the Kestenbaum procedures. Eyes are much quieter after recessions than after

Journal ofAAPOS Volume 1 Number 2June 1997 resections. There is something about operating on the belly of the muscle that provokes more swelling and discomfort, as most surgeons will agree. We hope to have some information on the actual comparative results of our operations in the future. Because not all clinicians have the oppommity to have eye movement recordings done before nystagmus operations, and because the possibility of periodic alternating nystagmus lurks, it would seem appropriate to do the Anderson procedure with only the recessions and warn the parents or patient that a second operation may be necessary. If periodic alternating nystagmus (PAN) is present, then the Anderson or Kestenbaum procedure will result in a large head turn in the opposite direction. Should that occur, an additional Anderson procedure (recessions on yoke muscles) on the other two horizontal muscles would be in order and should center the head position, s6 FUSIONAL VERGENCE AND NYSTAGMUS Vergenee demands have effects on the amplitude and frequency of nystagmns. This relationship was noted in Germany by Adelstein and Ciippers s7and brought to our attention in America byvon Noorden ssandvon Noorden and Wong 59with articles on the nystagmus blockage syndrome. Some patients dampen their nystagmns to the degree just necessary to attain the desired level ofaotityinvolved with the task at hand. This can result in a form of horizontal dissociated divergence with a variable horizontal strabismus. However, when eye movements were recorded in a paradigm such that subjects with idiopathic infantile nystagmus viewed Landolt rings in random sizes and orientation, only a small proportion of those patients with what we clinically had labeled nystagmus blockage syndrome dampened their nystagmus proportional to the size of the target. These studies were started by Hayashi, then in our laboratory, and continued by Gradstein, now in our laboratory. 6°More commonly, the subjects either blocked or did not block their nystagmus, and only rarely would subjects act like those with accommodative esotropia, who usually accommodate only well enough to discern the target at hand. Perhaps some with accommodative esotropia also either accommodate fully to the expected level or not at all. No study has been done to determine this. Years ago, I tried minus lenses in nystagmus patients because of my misguided notion that accommodative convergence would block the nystagmus. Dickinson ~ eventually proved that only voluntary or fusional convergence blocks nystagmus. Accommodative convergence has no effect on the amphtude, frequency, or foveation time of the patient. Given that, we need to follow the suggestion of Spielman 62in setting our goal to have all patients with nystagmus be exophoric. As the patient fuses the exophoria, the nystagmns is blocked. Minus lenses should therefore never be used, because they would make the subject more esophoric. Rather, plus should be crowded to make the patient as exophoric as possible and thus use fusional convergence, with the ensuing blockage of nystagmus. Similarly, the goal of any Kestenbaum or

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Anderson surgical procedure should be exophoria. Alina Zubcov, a former fellow with us, studied the surgical effectiveness in cases of idiopathic infantile nystagmus in Germany and here. We found that the surgical results with respect to increased visual acuity and increased foveation times were determined largely by the amount of exophoria produced (and fused) after the operation, rather than the type of surgical procedure.63 VISUAL ACUITIES OF PATIENTS WITH NYSTAGMUS Prediction of visual acuities of young patients with idiopathic infantile nystagmus is difficult, but some clinical observations may help. The natural history of developing visual acuity in subjects with idiopathic infantile nystagmus is typicallyone of an increasing level of vision until a plateau is reached at about 8 years. Do not be discouraged with a vision of 20/200 at 6 years; the vision frequently will rise to 20/50 or 20/40 by 8 years. Often a slight reduction of acuity occurs at about 20 years, followed by a slight increase of vision of about one line .everyone or two decades. In the measurement of visual acuity, we are interested in documenting patients' best vision at their preferred null point. Often, it is helpful to suggest that the subject move his or her head to the best position. Otherwise, the patient may keep the head in the straight, more cosmetically acceptable, position. Careful retinoscopy is essential. With the appropriate lenses, the visual acuity level can be maximized by projecting a whole visual chart of whatever type you use and asking the subject to continue to read the top line while viewing the entire chart as you bring smaller and smaller letters into view. Isolated letters or lines of letters are typically not seen as well. With the use of the top line of the full projected visual acuity chart, reproducible acuity measurements can be accomplished. We have noted that in the infant and young child, the presence of brisk OKN responses orthogonal to the nystagmus direction is a good prognostic sign. In other words, if the patient has horizontal nystagmus, a briskvertical OKN response is a good sign; conversely if the patient has vertical nystagmus, brisk horizontal OKN is a good sign that the subject may attain about 20/50 to 20/40 acuity. We have had considerable experience with sweep visual evoked potentials as a means of estimating visual acuity of infants. In general, the results have held up to the extent that the best level of acuity estimated by sweep visual evoked potentials is maintained at that level (and often better) as the child becomes verbal. 64'65 After Kestenbaum or Anderson procedures, nystagmus is often dramaticallyimprovedfor days to weeks. Improvement of vision after the operation is unpredictable. Sometimes it is a dramatic and maintained improvement; other times it improves only to regress to where it was before the operation. The chances of increased visual acuity as a result of operation are poor in patients older than 8 years; and when increased acuity does occur, regression to the original level typically takes place during the next few years.

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TREATMENT Biofeedback for Nystagmus The question of biofeedback training for the patient with nystagmus is often raised. We used an infrared eye movement detector system mounted on spectacle lenses with an aural feedback through small ear-speaker. The patient could learn to control the cosmetic jerking of the eyes, but, interestingly, no improvement of vision was seen. Also surprising was an increase in foveation time without a documented increase in visual acuity. 66, 67 Refraction

Refractive disorders, especially astigmatism, are more common in patients with nystagmus than in the general population. While Ohmi was in our laboratory, we68 examined patients with nystagmus and compared their astigmatism: first in amount and axis to the direction of the nystagmus and second with age-matched control subjects. We found no relationship between the direction of the axis of the nystagmus and the astigmatic axis, but did find twice as much astigmatism in those with nystagmus as in control subjects. Pragmatically precise retinoseopy is easy in patients with nystagmus. We thought that perhaps the constant jerking of the eye with the nystagmus might cause astigmatism, but no such correlation was found. The story with respect to the amblyopia brought about with the selective blur of certain meridians more than others has been hard to sort out, because the patients with nystagmus often have astigmatism and astigmatic amblyopia is well known. The important point is to carefully evaluate all patients with nystagmus retinoscopically. If the astigmatic error is greater than 1.50 D, logic suggests full prescription. The astigmatic correction is particularly important to the patient who has oblique astigmatism but vertical or horizontal nystagmus. If the nystagmus is parallel or orthogonal to the astigmatic axis, less blurring of the print will be seen than with the astigmatism off the axis of the nystagmus by 45 degrees. Because the astigmatism of young children may change fairly rapidly, retinoscopy should be performed frequently during the preteen years. Patients with astigmatism and nystagmus react to correction of their astigmatism in the same manner as do other patients with astigmatism; namely, they seldom appreciate the spectacles in the short term, but the visual acuity usually improves if they faithfullywear them. This point should be explained to the parents and patient to ensure compliance. When using sweep visual evoked potentials to assay the visual acuity of preverbal childrenwith idiopathic infantile nystagmus, the bars of the sweep should parallel the axis of the nystagmus.64 Failure to ensure this will result in underestimation of the child's vision. Correction of astigmatism, especially in high amounts, can be an important issue if the null point is eccentric, became astigmatic spectacle correction muses distortion in the peripheral cylindric lens areas. In such cases, it may be appropriate to suggest toric contact lenses or

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0

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1 second

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FIG. 16. Idiopathic infantile latent nystagmus. Note the decreasing velocity of the slow phase. The direction of the nystagmus changes despite fixation remaining at 0 degrees with only the o c c l u s i o n changing. The amplitude of the nystagmus differs depending on which eye is fixating. Note the flatness of the waveform when the visual axes are maximally away from the target.

to centralize the null point with an appropriate surgical procedure. Contact Lenses

Contact lenses are usually considered for most patients with nystagmus at some point if a significant refractive error is present. As is common with contact lenses, some love them and others put them aside. No definitive improvement in visual acuity with contact lenses rather than spectacles has been proved. Often the patient will have less nystagmus after first wearing contact lense; however, within a few months this improvement ceases and the nystagmus is back to where it was. In general, contact lens fittings in patients with nystagmus follow the same rules and suffer the same problems as fittings in the general population. OTHER NYSTAGMUS TYPES, CONFOUNDING OR CONCOMITANT Periodic Alternating Nystagmus Other forms ofnystagmus may confound the diagnosis and treatment of idiopathic infantile nystagmus. Any and all types of nystagmus may coexist. Perhaps the most serious form of nystagmus to miss is PAN. PAN seems to have its onset in much the same manner and time course as idiopathic infantile nystagmus, namely having wide triangular waveforms followed by small pendular movements and finally ending up with jerk nystagmus, but with a wandering null point as distinct from the fixed null point seen in most subjects with idiopathic infantile nystagmus. Clues to the presence of PAN are (1) conflicting notes in the records of the null point position; (2) the parent saying the patient has a head turn to one side when you observe an opposite head turn; and (3) response by the patient on being asked where he or she likes to

turn the head for best vision, "Sometimes to the right, sometimes straight ahead, and sometimes to the left." With any of these clues, patiently and continuously observe the patient as the null point changes, usually at a cycle of about 90 seconds but occasionally at a cycle as slow as 6 minutes. The cycle need not be symmetric; that is, the patient may keep the head to the right with gaze left at the null point for 15 seconds, and as the null point reaches the right, the patient moves the head left to be on the null point for 30 seconds. Whatever the times of right, straight ahead, or left null point positions, the same cycle timing remains fairly constant. If the subject has some element of nystagmus blockage, then the observation and characterization of the changing null point can be confusing, even on eye movement recordings. The danger of missing the infantile form of PAN is that if an Anderson or a Kestenbaum procedure is done to change what is erroneously thought to be an eccentric idiopathic infantile nystagmus null point, the null point is driven to the opposite direction from your recessions. That is, the null point after the operation is such that the subject has the null point stay to one side and demonstrates a severe, constant head turn. Surprisingly, the null point stays in one eccentric position and does not wander after a Kestenbaum procedure. Further operation to recess the resected muscles usually alleviates the problem. After such secondary large recessions, the surgeon has ejected retroequatorial recessions of all four horizontal muscles. If an Anderson procedure was done for a missed PAN, the spared horizontal muscles should be recessed. In either instance, you are converting to four muscle retroequatorial recessions, which seems the best of procedures for PAN at present. Gradstein, of our laboratory, reported on our experience with PAN at the most recent Academy meeting, s8Note that the PAN discussed here is infantile in onset. The PAN that results from central nervous

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79

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system midbrain insult is often responsive to baclofen. Whether the four-musde recession is suitable for PAN caused by a neurologic insult has not been resolved at this time.

Spasmus Nutans Asymmetry of the two eyes' movements with respect to either phase, direction, or amplitude is indicative of spasmus nutans. The onset of spasmus nutans varies from 1 to 7 years of age. Head nodding was found by Gottlob and coworkers69 in our laboratory to be a compensatory mechanism that uses the vestibular system to drive the eyes in the same direction, thus temporarily alleviating the asymmetry of the eyes' movements. The head nodding may be vertical, horizontal, or oblique. Some of our colleagues have discounted the frequency of chiasmal gliomas as causal to spasmus nutans. W e find a glioma in about one of every seven patients referred to us with spasmus nutans, so I strongly favor magnetic resonance imaging for all patients with spasmus nutans. 7°, 71 Pediatric oncologists are not in agreement on the exact treatment for such patients, but the aggressive treatments given at Children's Hospital in Philadelphia have impressed me.

Manifest Latent Nystagmus Manifest latent nystagmus is easily missed or misdiagnosed unless we search for the telltale characteristics. Its importance lies in the fact that it is the one truly treatable variety of nystagmus. Thewaveformis that ofdecreasingvelocityofthe slow phase of the nystagmus, with the direction constant until it reverses as the occlusion of each eye is changed. The fast phase is toward the fixing eye. Latent nystagmus remains latent only as long as the eyes are fusing or the patient believes his or her eyes to be fusing. An occasional patient will have an uncanny ability to turn latent into manifest by turning the fusion on and off. Latent nystagmus is symmetric; both eyes simultaneously have the same amplitude, frequency, and phase. However, the

nystagrnic responses brought about with occlusion of each eye may be different in amplitude and frequency and are always different in direction. For example, when the right eye is covered the latent nystagmus will become manifest as long as the right eye is covered, and it will beat toward the left, fixing eye. The right eye will be beating to the left identically with the left eye. When the cover is switched to the left eye and the right eye is uncovered, the nystagmus will start its beat toward the right. The amplitudes during the covering of the right and left eyes may be quite dissimilar (Figure 16). Simonsz 72 pointed out that the dilemma of patches for amblyopic patients with latent nystagmus is solvable. Fommately, he discovered that although patching the good eye causes the nystagmus to have greater intensity than does patching the poorer eye, that will reverse itself if the good eye is patched for 48 hours or more continuously. Thus, the parents may volunteer the observation that the nystagmus was reduced greatly after patching of 48 hours. Latent nystagmus may cause problems in measuring a strabismus or phoria because the fast or slow phase may mimic the fixation shift caused by the shifting occlusion. This problem can be solved easily with the use of a +4.00 lens, not only as an occluder for the measurement of the visual acuity but also as an alternating occluder for the cover and alternate cover test for detection ofphoria or tropia. Switch the +4.00 back and forth as a cover to measure any phoria or tropia. One can use prisms in addition to the +4.00 occluder to measure any phoria or tropia. This is schematically demonstrated in Figures 17 and 18. If a patient with manifest latent nystagmus has an alternating esotropia, the direction of the nystagmus will depend on which eye the patient is fixing with (Figure 19). It is well to regard manifest latent nystagmus has having two null zones, because the slow phase changes with fixation and is medial with respect to the fixing eye. The null zone is so medial that it cannot be demonstrated with a reversal of

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Journal ofAAPOS Volume i Number 2June 1997

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0

0

oooo

I

0o

0 °

'Right 5o • Left

OS

1 :second

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6AE 0 °

O°

I

FIG. 18. The diagram shows esotropia with fixation being alternated with a +4.00 lens used as an occluder. The plus lens often allows the nystagmus to remain latent despite the esotropia. The commonly seen abnormal retinal correspondence may explain why the nystagmus remains latent with the plus lenses. Prisms can be used to quantitate the esotropia or exotropia during such alternate occlusion with a convex lens.

I second

I second

FIG, 19. The diagram represents a spontaneous alternating esotropia with manifest latent nystagrnus.

Note the change of direction as the patient changes from right to left esotropia.

nystagmus. Because the preferred null zone of manifest latent nystagmus is medial and those with alternating esotropia often prefer crossed fixation, such patients will cross-fixate and exhibit the fast-phase jerking the eyes laterally to the medially fixing eye. This configuration of position and fixation can mimic idiopathic infantile nystagmus, and a search for manifest latent nystagmus should be made. Any time manifest latent nystagmus is identified, it is well worth pursuing the possibility of alignment of such eyes to attempt to turn the nystagmus to a state of latency with strabismus surgical correction. I have been pleased with such attempts done with adjustable sutures and topical anesthesia supplemented with light dissociated anesthesia. Sterile +4.00 lenses in the operating room are used as

indicated previously during the adjustment of the recessed muscles. Albinism is well known to often have associated nystagmus. I would like to emphasize two points. First, no matter the skin or iris color, always check the iris for defects of transillumination in patients with nystagmus. Second, remember that you will find an occasional albino without nystagmus, and of course you will find many patients with idiopathic infantile nystagmus but without albinism. GENETICS Idiopathic infantile nystagmus may be inherited as either a recessive dominant or an X-linked trait. The gene seems to be 6p12, but more work is in progress. 73

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CONCLUSIONS You may surmise from my enthusiasm that I suspect that the more we learn about nystagmus, the closer we will come to discovering the details of normal eye movement development. The extended slow phases are an exciting new finding and appear to explain the adult waveforms as being composed of evolutionary phase I and II waveforms. Better and more eye movement recordings will help us dismiss the folklore from nystagmus and document results of the treatments we offer to our patients with this condition. Thankyou for the opportunity of ruminating on my fascination with idiopathic infantile nystagmus. References 1. Reinecke RD, Cogan DG. Standardization of objectivevisual acuity measurements: optokinetic nystagmus vs Snellen acuity. Arch Ophthalmol 1958;69:418-21. 2. Costenbader FD. Child and the ophthalmologist. Med Ann D C 1934;3:127-30. 3. Costenbader FD. Ocular findings in newborn--preliminarystudy. Va Med Monthly 1940;67:217-22. 4. Costenbader FD. Ocular emergencies in general medical practice. Med Ann D C 1941;10:472-6. 5. Costenbader FD. Foreign body in the lacrimalsac. AmJ Ophthalmol

1945;28:754-6. 6. Costenbader FD. Causes of failure in the treatment of squint. Am J Ophthalmol 1945;28:1123-32. 7. Holmes DB, Costenbader FD. Bilateral retinoblastoma: case report. Clin Proc Child Hosp 1946;2:192-5. 8. Costenbader FD. Common ocular affectionsof childhood. Med Ann D C 1947;16:366-71. 9. Costenbader FD. Ocular affections of newborn. W V Med J 1948;44:36-40. 10. Costenbader FD, Bair D, McPhail A. Vision in strabismus: a preliminary report. Arch Ophthalmol 1948;40:438-53. 11. Costenbader FD. Treatment of crossed eyes. Sight Saving Rev 1949;19:84-8. 12. Costenbader FD. Management of concomitant strabismus. South MedJ 1949;42:617-23. 13. Parks MM, Costenbader FD. Craniofacial dysostosis (Crouzon's disease). Am J Ophthalmol 1950;33:77-82. 14. Costenbader FD. Accommodometer. Trans Am Acad Oph~almol 1950;54:362-4. 15. C°stenbader FD" Factors in the cure °f squint" In: AllenJH' editor" Strabismus ophthalmic symposium (I). St Louis, Mosby; 1950. p. 367-76. 16. Costenbader FD. What to do about strabismus. Ohio Med J 1953;49:892-5. 17. Costenbader FD, Bair DR. Strabismus surgery--monocular or binocular? Arch Ophthalmol 1954;52:655-63. 18. Costenbader FD. Fit-over frame. Trans Am Acad Ophthalmol Otol 1957;61:224. 19. Costenbader FD. The improved accommodometer. Trans Am Acad Ophthalmol Otol 1957;61:225-6. 20. C°stenbader FD" Acc°mm°dative es°tr°pia: principles °f treatment" Trans Am Acad Ophthalmol Otol 1957;61:390-4. 21. Costenbader FD, Albert DG. Conservatism in the management of congenital cataract. Arch Ophthalmol 1957;58:426-30. 22. Costenbader ED, Albert DG. Spontaneous regression of pseudoparalysis of the inferior oblique. Arch Ophthalmol 1958;59:607-8. 23. Costenbader FD, Albert DG. The management of strabismus. Pediatr Clin North Am 1958;Feb:153-68. 24. Costenbader FD. Myasthenia gravis in childhood. Med Ann D C 1958;27:227-30.

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25. Costenbader FD. Office evaluation of vision in children. Pediatrics 1959;23:985-9. 26. Apt L, Costenbader FD, Parks MM, Albert DG. Catgut allergy in eye muscle surgery I. Correlation of eye reaction and skin test using plain catgut. Arch Ophthalmol 1960;63:30-5. 27. Costenbader FD. The management of convergent strabismus. In: Allen JH, editor. Strabismus ophthalmic symposium (I). St Louis: Mosby; 1950. p. 334-48. 28. Costenbader FD. Infantile esotropia. Trans Am Ophthalmol Soc 1961;59:39%429. 29. Costenbader FD, Kwitko ML. Congenital glaucoma. Clin Proc Child Hosp 1961;17:100-9. 30. Apt L, Costenbader FD, Parks MM, Albert DG. Catgut allergy in eye muscle surgery II. Correlation and comparison of eye reaction and skin test after the use of plain and chromicized catgut. Arch Ophthalmol 1961;65:474-80. 31. KwitkoML, Costenbader FD. Urea therapy in congenital glaucoma due to secondary hyphema. Can Med AssocJ 1962;86:447-9. 32. Kwitko ML, Costenbader FD. Glaucoma due to secondary hyphema: a report of two cases treated with intravenous urea. Am J Ophthalmol 1962;53:590-2. 33. Costenbader FD, Mousel DK. Cyclic esotropia. Arch Ophthalmol 1964;71:180-1. 34. Costenbader FD, Mousel DK. Functional amblyopia in early adolescence. Clin Proc Child Hosp 1964;20:49-58. 35. Costenbader FD, Kertesz E. Relaxing procedures of the inferior oblique: a comparative study. Am J Ophthalmol 1964;57:276-80. 36. Costenbader ED. Symposium:The 'A' and 'V' patterns in strabismus: summary and conclusions. Trans Am Acad Ophthalmol Otol 1964;68:385-6. 37. Costenbader FD. Symposium:The 'A' and 'V' patterns in strabismus: introduction. Trans Am Acad Ophthalmol Otol 1964;68:354-5. 38. Burian HM, Cooper EL, Costenbader FD. The 'A' and 'V' patterns in strabismus: treatment. Trans Am Acad Ophthalmol Otol 1964;68:375-84. 39. Costenbader FD. Motor fusion in strabismus. Diagnosis and clinical significanceof the fusionalvergences.Am Orthopt J 1965;15:14-20. 40. Costenbader FD. Early management of strabismus. Am J Ophthalmol 1965;59:950-1. 41. Albert DG, Costenbader FD. Surgery of the vertical recti. South MedJ 1965;58:383-7. 42. Hiatt RL, Costenbader FD, Albert DG. Clinical evaluation of congenital myopia. Arch Ophthalmol 1965;74:31-5. 43. Dell'Osso LF, Daroff RB. Congenital nystagmus waveforms and foveation strategy. Doc Ophthalmol 1975;39:155-82. 44. Leigh RJ, Rushton DN, Thurston SE, Hertle RW, Yanigios SS. Effects of retinal image stabilization in acquired nystagmus due to neurologic disease. Neurology 1988;38:122-7. 45. Zubcov AA, Reinecke RD, Gottlob I, Manley DR, Calhoun JH. Treatment of manifest latent nystagmus. Am J Ophthalmol 1990;110:160-7. 46. Abel LA, Parker L, DaroffPL, Dell'Osso LF. End-point nystagmus. Invest Ophthalmol Vis Sci 1978;17:539-44. 47. GoldsteinHP. Extended slow phase analysisoffoveation, waveform and null zone in infantile nystagmus [abstract]. Invest Ophthalmol Vis Sci 1995;36:835. 48. Gottlob I. Infantile nystagmus development documented by eye movement recordings. Invest Ophthalmol Vis Sci 1997;38:767-73. 49. Reinecke RE). Development of congenital and infantile nystagrnus. In: Tusa RJ, Newman SA, editors. Neuro-ophthalmological disorders: diagnostic work-up and management. New York: Marcel Dekker; 1995. p. 175-85. 50. Reinecke RD, Guo S, Goldstein HP. Waveform evolution in infantile nystagmus: an electro-oculo-graphic study of 35 cases. Binoc Vis 1988;3:191-202. 51. Goldstein HP, Gottlob I. Infantile nystagmusslow-phasewaveforms [abstract]. Invest Ophthalmol Vis Sci 1992;33:2298.

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52. Bedell HE, White JM. The torsional component of idiopathic congenital nystagmus [abstract]. Invest Ophthalmol Vis Sci 1995;36:838. 53. Chandhry NA, Gonzales C, Lee MS. EOG documentation of an unique case of congenital vertical nystagmus [abstract]. Invest Ophthalmol Vis Sci 1996;37:1281. 54. Dell'Osso LF, Williams RW, Jacobs JB, Erchul DM. Achiasmatic mutant Belgian sheepdogs: an animal model for congenital nystagmus [abstract]. Invest Ophthalmol Vis Sci 1996;37:1032. 55. Goldstein HP, Gottlob I, Fendick MG. Visual remapping in infantile nystagmus. Vis Res 1992;32:1115-24. 56. Gradstein L, Reinecke RE), Wizov SS. Idiopathic periodic alternating nystagmus: diagnosis and management [abstract]. Ophthalmology 1996;103:122. 57. Adelstein F, COppers C. Zum problem der echten und scheinbaren abducensl~hmung (das sogenannte "Blockierungssyndrom"). In: Enke F, editor. Stuttgart, Germany: Augenmuskellghmungen; 1966. p. 271-8. 58. yon Noorden GK. The nystagmus compensation (blockage) syndrome. Am J Ophthalmol 1976;82:283-90. 59. von Noorden GK, Wong SY. Surgical results in nystagmus blockage syndrome. Ophthalmology 1986;93:1028-31. 60. Gradstein L, Goldstein H2, Hayashi T, Wizov SS, Reinecke RD. Changes of nystagmus characteristics following acuity demands in idiopathic infantile nystagmus [abstract]. Invest Ophthalmol Vis Sci 1996;37:1030. 61. Dickinson CM. The elucidation and use of the effect of near fixation in congenital nystagmus. Ophthalmic Physiol Opt 1986;6:303-11. 62. Spielman A. Surgery to dampen nystagmus. In: Spiritus M, editor. Transactions of the 22nd meeting of the European Strabismological Association. Cambridge, United Kingdom: Aeolus Press; 1996. p. 286-93.

Journal ofAAPOS Volume 1 Number 2June 1997 63. Zubcov AA, Stark N, Weber A, Wizov SS, Reinecke RD. Improvement of visual acuity after surgery for nystagmus. Ophthalmology 1993;100:1488-97. 64. Guo S, Fendick MG, Reinecke RD. Infantile nystagmus: grating acuity measured using swept spatial frequency VEPs and psychophysics [abstract]. Invest Ophthalmol Vis Sci 1988;29:346. 65. Gottlob I, Fendick MG, Guo S, Zubcov AA, Odom JV, Reinecke RD. Visual acuity measurements by swept spatial frequency visualevoked-cortical potentials (VECPs): clinical application in children with various visual disorders. J Pediatr Ophthalmol Strabismus 1990;27:40-7. 66. Mezawa M, Ishikawa S, Ukai K. Changes in waveform of congenital nystagmus associated with biofeedback treatment. Br J Ophthalmol 1990;74:472-6. 67. Ciuffreda KJ, Goldrich SG, Neary C. Use of eye movement auditory biofeedback in the control of nystagmus. Am J Optom Physiol Opt 1982;59:396-409. 68. Ohmi G, Reinecke RD. Astigmatism of nystagmus subjects [abstract]. Invest Ophthalmol Vis Sci 1993;34:1125. 69. Gottlob I, Zubcov AA, Wizov SS, Reinecke RD. Head nodding is compensatory in spasmus nutans. Ophthalmology 1992;99:1024-31. 70. Gottlob I, ZubeovA, Catalano R, Reinecke RD, Koller HP, Calhoun JH, et al. Signs distinguishing spasmus nutans with and without CNS lesions from infantile nystagmus. Ophthalmology 1990;97:1166-75. 71. Gottlob I, Wizov SS, Reineeke RD. Spasmus nutans: a long-term follow-up. Invest Ophthalmol Vis Sei 1995;36:2768-71. 72. Simonsz HJ. The effect of prolonged monocular occlusion on latent nystagmus in the treatment of amblyopia. Doe Ophthalmol 1989;72:375-84. 73. Kerrison JB, Arnould VJ, Barmada NLM, Koenekoop RK, Schmeekpeper BJ, Maumenee IH. A gene for autosomal dominant congenital nystagmus localizes to 6p12. Genomics 1996;33:523-6.