Waveform Characteristics of Manifest Latent Nystagmus

Abstract

purpose. To examine the waveform characteristics of 37 subjects with manifest latent nystagmus (MLN) and determine the manner in which visual feedback influences the nature of the waveform.

methods. Binocular recordings of the eye movements of all subjects were undertaken using an infrared tracking system. Subjects viewed the target binocularly and monocularly in primary gaze. The effect of visual feedback on the nature of the MLN waveform was examined by either removing the fixation target or by progressively stabilizing the target in relation to the retina. This progressive stabilization was achieved by feeding back the eye movement signal to move an otherwise stationary target.

results. Four types of MLN were distinguished on the basis of the fixation characteristics seen during binocular and monocular viewing. First, under binocular viewing conditions, subjects could theoretically exhibit stable fixation (type 1 MLN). In addition, three other MLN types were recorded during binocular fixation: conjugate horizontal square-wave jerks (type 2 MLN), conjugate torsional nystagmus (type 3 MLN) and conjugate horizontal jerk MLN waveforms (type 4 MLN). Monocular viewing always gave rise to a conjugate horizontal jerk MLN waveform for each of the four types of MLN. More than 80% of the subjects exhibited either type 3 or type 4 MLN, both of which conform with previous classic descriptions of MLN. Much less common was type 2 MLN. Type 1 MLN (conventionally referred to as a latent nystagmus) appeared to be a rare occurrence. In addition to the two classic linear and decelerating MLN slow phases, four additional slow-phase shapes with either saccadic or pendular elements were recorded and described. Removing visual feedback generally reduced the mean slow-phase velocity and the number of fast phases. For each subject some variability of the slow-phase class was documented from session to session.

conclusions. Four types of MLN have been described. Their differences are based on their binocular oculomotor behavior, and it is proposed that type 1 MLN and type 4 MLN represent the absolute states and types 2 and 3 the intermediate levels of the MLN spectrum. All types of MLN appear to be strongly visually driven and are largely dependent on the attentional state of the subject and the target conditions. Six different classes of slow phase were found among the four MLN types. The introduction of visual feedback had an immediate effect on the subsequent slow phase or fast phase. It is likely that adaptation mechanisms are in play after a period of visual feedback.

The two most common types of benign nystagmus seen in infancy are congenital nystagmus (CN) and manifest latent nystagmus (MLN). ^{1 2 3 4} In both conditions the oscillations are typically conjugate, horizontal, and jerk. Differential diagnosis is made on the basis that the CN slow phases are typically of an increasing exponential velocity form, whereas in MLN the form is decelerating or linear. ^{5 6} In addition to its distinguishing slow phase, the fast phase of MLN always beats toward the viewing eye. MLN is also closely associated with the presence of strabismus and dissociated vertical divergence. ⁶  

A third, but less common, type of infantile nystagmus is latent nystagmus (LN). ^{2 5 6 7} In this disorder, during binocular viewing conditions it is said that the eyes are steady, but during monocular viewing, bilateral conjugate jerk nystagmus becomes manifest. As in MLN, the LN slow phase is either a decreasing or linear velocity, with the fast phase directed toward the viewing eye. Our experience over the past 20 years in examining more than 300 subjects with nystagmus has been that MLN is not uncommon (10%–15%), whereas LN is a rare occurrence. This is in agreement with other reports. ^{4 5 6}  

Over the years, we have carefully examined the eye movements of 37 individuals with MLN and have found that the oscillations do not fall neatly into the prevailing definitions. The purpose of this study was therefore to investigate the nature of MLN and describe the waveform characteristics in detail. To this end, we examined whether there is just one type of MLN and only two possible classes of slow phases. We also considered where LN should be classified within the spectrum of infantile nystagmus. Finally, by varying visual feedback, we examined how visual signals influence the MLN oscillation. In our results, MLN was a complex oscillation, and the nature of MLN was greatly affected by the presence of a target and by the amount of retinal image movement experienced by the subject. 

Materials and Methods

Subjects

Thirty-seven subjects (aged 18–67 years) with MLN took part in this study. All underwent full clinical investigation (Table 1) . The tenets of the Declaration of Helsinki were followed in this research program. Informed consent was obtained from all subjects after the nature and possible consequences of the study had been explained. 

Eye Movement Recording

Binocular horizontal and vertical eye movements were monitored using a head-mounted infrared limbal tracker (IRIS 6500; Skalar Medical, Delft, The Netherlands). The analog output was filtered through a 100-Hz low-pass filter, digitized to 12-bit resolution, and then sampled at between 1- and 5-msec intervals. The system was linear to ±20° and had a resolution of 0.03°. Eye movements were calibrated by presenting a pursuit stimulus that moved horizontally over a range of ±10° in a sinusoidal manner at 0.24 Hz for three cycles or 0.32 Hz for four cycles. Subjects were instructed to follow this as accurately as possible and by subsequently plotting eye position against target position, the eye position data were calibrated. A chin rest with supplementary cheek supports was used to stabilize the head position. Head movements were well controlled in relation to earth (<0.1° in amplitude). Fundus video recordings were also performed on a selected number of subjects to assess the torsional components of any oscillation. 

Experiment 1: The Nystagmus Characteristics under Binocular and Monocular Viewing Conditions

Both eyes were recorded when 37 subjects fixated a composite bull’s eye and cross target (5.5°) which was back projected onto a screen that subtended 105° × 41° when viewed from 114 cm. ⁸ The stationary target was presented in the primary position. After fixation was recorded with both eyes open, each eye was fully occluded in turn. Subjects were instructed to look at the center of the target. The nature of the slow phase was judged on the basis of eye velocity and eye acceleration profiles. 

Experiment 2: The Effect of Visual Feedback on MLN

The characteristics of MLN were examined in 11 subjects under three test conditions: target present, target absent, and target under servocontrol. When the target was absent, the subject was requested to direct the gaze at its remembered position. The amount of retinal image motion experienced by each subject was controlled by varying the amounts of eye position feedback to a mirror galvanometer and thus target position. Feedback gain (fbg) is defined as target velocity/eye velocity. When the target position was decoupled from the subject’s nystagmus the fbg was equal to 0. Feedback gains greater than 0 but less than +1.0 decreased the retinal image movement. The retinal image was stabilized when the fbg was equal to +1.0. Subjects were instructed to keep the target clear and on the screen throughout each viewing period. All investigations with the target under servocontrol were performed under monocular viewing conditions only. Further details of the experimental arrangement can be found in our recent publication. ⁸  

Results

MLN Waveforms

Our waveform analysis indicated that MLN is not a single entity but is best divided into four distinct categories (Fig. 1) . These categories were distinguished on the basis of the fixation characteristics seen during binocular and monocular viewing. Type 1 MLN represents the absolute case in which the eyes are stable during binocular viewing, but when either eye is covered, the eyes oscillate in a manner consistent with MLN. In the past, this MLN type has been referred to as LN ^{2 3 4 5 6 7.} Of the 37 subjects in our study, none exhibited type 1 MLN. 

In type 2 MLN, horizontal conjugate square-wave jerks are seen during binocular viewing (Fig. 2) , whereas type 3 MLN exhibits torsional nystagmus during binocular viewing (Fig. 3) . As in type 1 MLN, subjects with type 2 MLN and type 3 MLN always displayed conjugate horizontal jerk MLN oscillations during monocular viewing. A subject with type 4 MLN showed decelerating or linear slow-phase jerk MLN waveforms during both binocular and monocular viewing (Fig. 4) . That is, unlike MLN types 1, 2 and 3, the type 4 waveform shape was unaffected by monocular occlusion. 

Occasionally some subjects displayed compound oscillations. For example, the eye movements of a subject could exhibit elements of both type 2 and type 4 MLN during binocular viewing (Fig. 5) . We called this a type 2–type 4 MLN hybrid. 

The distribution of the four different MLN types found in our randomly chosen subject pool are shown in Figure 6 . Type 3 MLN (32.4%) and type 4 MLN (48.7%) were found to be the most common. No type 1 MLN was found in our study population. Two subjects exhibited type 2 MLN in combination with either type 3 or type 4 MLN. Apart from subjects belonging to the MLN hybrid group, subjects exhibited a single constant MLN type throughout all recording sessions. 

The MLN Slow Phase

Six classes of MLN slow phases were distinguished (Fig. 7) . Apart from the classic linear slow phase (class IIA) and decreasing-velocity slow phase (class IA), we identified two with saccadic elements (classes IB and IIB) and two with pendular components (classes IIIA and B). A class I MLN slow phase has either a conventional decreasing-velocity slow phase or a decreasing-velocity slow phase with a preceding saccade. Class II MLN slow phases have either a linear slow phase or a linear slow phase with a preceding saccade, and a class III MLN slow phase exhibits strong pendular components. The intensity of the pendular component determines whether the class III MLN slow phase is a class IIIA or a class IIIB MLN slow phase. 

The relative incidences of the six slow phases strongly depended on the viewing conditions and the MLN type of the subject. Histograms illustrating the percentage of incidences of oscillations seen when three subjects with different MLN types viewed a target in the primary position are shown in Figure 8 . The distributions seen during binocular viewing clearly defined the MLN type. As expected, the distributions changed dramatically during monocular viewing with none of the MLN types displaying a unique distribution. The distributions of the classes of slow phases (classes I–III) seen during monocular viewing occasionally varied from session to session. 

The Effect of Visual Feedback on the MLN Slow Phase

Figure 9 illustrates the eye movement traces when three subjects with types 2, 3, and 4 MLN monocularly viewed a target, in the primary position. The effects of either removing the target or stabilizing the retinal image are shown respectively in columns two and three. For all three MLN types, removal of the target reduced the intensity of the MLN and decreased the mean slow-phase velocity. The application of a fbg of+ 1.0 also modified the nystagmus. 

In an effort to explore the effect of visual feedback more systematically, three feedback gain (fbg) conditions were investigated. These were 0.0, 0.5, and 1.0 fbg and were equivalent to normal retinal image motion (fbg = 0), a 50% reduction in retinal image motion (fbg = 0.5), and a stabilized retinal image state (fbg = 1.0). Figure 10 illustrates how these three test conditions affected the class of MLN slow phases for three subjects with types 2, 3, and 4 MLN. For subjects with type 2 MLN, the +0.5 and +1.0 fbgs greatly modified the subjects’ oscillations which reverted to those seen normally during binocular viewing (i.e., square-wave jerks). In contrast, the +0.50 and +1.0 fbg conditions did not appear to change the incidence of the dominant MLN slow-phase class for subjects with type 3 and type 4 MLN. 

The response to the introduction of a change in visual feedback appeared to be specific to each subject, and Figure 11 illustrates each of the six variations that we found. In Figure 11A the subject who had type 3 MLN never exhibited any apparent change in the right-beating MLN. In comparison, the monocular left-beating nystagmus seen before the onset of feedback in a subject with type 2 MLN, changed to square-wave jerk oscillations when feedback was introduced (Fig. 11B) . This response, whereby the monocular oscillations either partially or completely reverted to the binocular state was typical of all subjects with type 2 MLN. The same response was also elicited when the target was removed during binocular viewing. Of note, when the feedback was introduced, there was often a delay of up to 3 seconds before the onset of the square-wave jerks. Thereafter, for the subject in Figure 11B the left eye slowly drifted nasally 4° or so. In the third feedback-related affect (Fig. 11C) , the introduction of feedback to a subject with type 3 MLN brought about a large increase in the amplitude of the right-beating MLN. Once again, there was a measurable latency—2 seconds in this case—before the onset of the large-amplitude oscillations. Figure 11D illustrates how the introduction of a +1.0 fbg to a subject with type 4 MLN brought about a shift in the eye position of approximately 8°. This shift was mediated by leftward saccades. By comparison, a subject with type 3 MLN (Fig. 11E) who also showed a gaze shift, achieved the new eye position by a series of slow eye movements. Finally, a subject with type 4 MLN (Fig. 11F) exhibited a change in the nystagmus intensity which is superimposed on a large-amplitude, low-frequency slow eye movement. 

The saccade-mediated gaze shift seen in Figure 11D for the subject with type 4 MLN was investigated further by examining how the level of the fbg influenced the change in the eye position. Figures 12A 12B 12C 12D illustrate that the shift was directly related to the level of the fbg, so that the +1.0 fbg condition brought about a 6° shift in the eye position. 

Removal of the visual feedback brought about a gaze shift in the direction opposite to that seen when the feedback was introduced. This eye position change was achieved by either an extended slow phase (Figs. 13A 13B ) or a saccade (Fig. 13C) . 

Discussion

The MLN Waveform

The purpose of this study was to perform both a qualitative and quantitative examination of the waveform characteristics of MLN. We believe that the four MLN types described in this study represent a continuum from the stable binocular state of a subject with type 1 MLN to the sustained MLN oscillations seen during binocular viewing for a subject with type 4 MLN. These four categories have been based on the binocular and monocular fixation characteristics of 37 subjects with MLN when they viewed a stationary target presented in the primary position. 

In common with past reports, we concur that type 1 MLN (or LN) is an uncommon occurrence. ² It is likely that in the past, small-intensity type 2 or type 3 MLN oscillations were classified as a type 1 MLN because of the absence of high-resolution eye movement recordings. The conventional waveform descriptions of MLN are typical of type 3 and type 4 MLN. ^{4 5 6} In both cases a nystagmus is present during both binocular and monocular viewing. It is the change of the nystagmus from a torsional to a horizontal decelerating or linear slow-phase jerk oscillation seen in type 3 MLN that differentiates it from type 4 MLN. In the latter case, the nystagmus remains principally in the horizontal plane, and the slow phase remains decelerating or linear during both binocular and monocular viewing. Using fundus video oculography, we found that in type 3 MLN, the torsional nystagmus seen when both eyes were open was no longer detectable during monocular fixation when the nystagmus motion was in the horizontal plane. 

The presence of square-wave jerks during binocular viewing defines type 2 MLN and differentiates it from the other three types. It is tempting to propose that type 2 MLN represents a stage between types 1, 3, and 4 MLN and may reflect the differences in the underlying mechanisms responsible for each of the four categories of MLN. In a previous study we stated that the incidence of physiological square-wave jerks in the normal population is approximately 30%. ⁹ These saccadic oscillations were more commonly seen when otherwise oculomotor normal subjects viewed the target in mesopic conditions or when they were tired. To date, there have been two reports of square-wave jerks preceding the postnatal appearance of congenital nystagmus. ^{10 11}  

Occasionally, our subjects intentionally or unintentionally changed from their binocular state to looking out of either eye. For subjects with type 2 or type 3 MLN, this immediately changed the binocular oscillations (i.e., square-wave jerks or torsional nystagmus) into an oscillation with an MLN waveform and, depending on the fixing eye, a change in the direction of the fast phase was noted. As can be seen in Table 1 , none of the 37 subjects who took part in this study was truly binocular, because all exhibited squints of one sort or another and more than 30% had symmetrical or asymmetrical dissociated vertical divergence. 

The MLN Slow Phase

None of the six classes of MLN slow phases described in this study had an increasing velocity. The variety of slow phases that we have found in MLN support the findings of earlier reports. ^{3 6 12} The microsaccades seen in the class IB and class IIB slow phases have been previously shown to be saccadic in nature. ⁹ In agreement with other studies we encountered, on the rare occasion, odd nystagmus beats with a runaway slow phase. ^{3 4 5 6} The histograms seen in Figure 8 clearly illustrate that each subject did not exhibit a single unique MLN slow phase class, but rather displayed a variety of classes, with one being dominant. Great variations in the distribution of the classes of MLN slow phase were apparent within our subject group. The great variability of MLN slow phases is not surprising and is akin to that seen in subjects with congenital nystagmus, when they can exhibit up to four different congenital nystagmus waveforms. ^{2 13 14} In both, the case of congenital and manifest latent nystagmus, the slow phase appears to be strongly influenced by the presence of the target (Figs. 9 10) and to a lesser degree whenever feedback is applied to the target (Fig. 11) . In a recent study we have shown that during periods of visual disengagement, such as +1.0 fbg, there can be a decline in the slow-phase eye velocity. ¹² In addition, and in common with previous studies, ^{6 12 13 14 15 16} we propose that attentional and/or voluntary mechanisms can drive MLN or CN. 

The eye position shifts triggered by either the introduction of or the removal of visual feedback is idiosyncratic. Apart from subjects with type 2 MLN, there appears to be no specific response for any one of the other MLN types. However, the responses may provide insights into saccadic programming. ¹⁷ Consider, for example, Figure 11D where the switching off of visual feedback occurs before the quick phase of the MLN. At this time the saccadic amplitude and velocity have already been programmed, yet the saccadic amplitude is modified midflight by the change in visual feedback. This is compatible with the nonballistic behavior of some saccades, and a sampled data model of saccadic generation predicts that it is possible to increase the magnitude of a saccade during the first 70 msec of saccadic programming. ^{4 18 19 20}  

It is noteworthy that the eye position shifts seen after the removal of feedback were generally greater than those seen in response to the original introduction of visual feedback (Fig. 13) . This may well reflect adaptation mechanisms, so that during feedback there was a modification of slow eye movement control which became inappropriate once the feedback was switched off. That is, the slow phases that make up an MLN are not simply the result of a passive drift between fast phases but are part of a continuous active control system. 

 Supported by scholarships from the College of Optometrists and UMIST (CJS).

 Submitted for publication November 16, 1999; revised February 15, May 22, and July 24, 2000; accepted July 25, 2000.

 Commercial relationships policy: N.

 

Table 1.

 

Clinical Details of the Subjects with MLN

Subject	Age/Sex	Binocular Status	Visual Acuity (LogMAR)					MLN Type
						Binocular	RE		LE
1	32M	LesoT	+0.30	+0.30	+0.50	2
2	30F	RexoT	+0.30	+0.60	+0.21	4
3	36M	RexoT	+0.50	+0.60	+1.00	4
4	22F	LesoT	−0.10	+0.60	+0.60	3
5	32M	ResoT	+0.60	+0.80	+0.80	4
6	35M	LesoT	0.00	+1.00	+1.00	4
7	27M	LesoT, L hyper T, DVD	−0.10	0.00	+0.50	3
8	18F	LesoT	+0.20	+0.30	+0.40	3
9	12F	LesoT	+0.10	+0.10	+0.20	4
10	22F	ResoT, R hypo T	0.0	+0.30	−0.10	2
11	18M	ResoT, R hypo T	+0.30	+0.70	+0.30	3
12	9F	ResoT, DVD	+0.30	+0.60	+0.30	4
13	7F	ResoT	+0.50	+0.50	+0.50	4
14	15M	ResoT	+0.80	+0.90	+0.80	3
15	53M	LexoT, DVD	−0.10	0.00	−0.10	2
16	11M	ResoT	+0.20	+0.30	+0.20	4
17	8F	ResoT	−0.10	LP	−0.10	4
18	17F	ResoT, DVD	0.00	+0.80	+0.80	2
19	12M	ResoT, R hyper T	−0.10	LP	−0.10	4
20	20M	ResoT	0.00	LP	0.00	4
21	60F	ResoT	+0.20	+0.60	+0.30	4
22	12M	LexoT, L hypo T, DVD	+0.20	+0.50	+1.00	3
23	19M	LesoT	0.00	0.00	PL	3
24	24F	RexoT, DVD	+0.30	+0.60	+0.30	4
25	11M	RexoT, DVD	0.00	+0.60	+0.30	3
26	36F	LexoT, L hypo T	−0.10	−0.10	+0.40	4
27	31M	LesoT	+0.40	+0.40	+0.50	4
28	17F	LexoT, DVD	+0.20	+0.20	+0.40	3
29	17M	RexoT	+0.60	+0.60	+0.60	4
30	19F	RexoT, R hypo T, DVD	−0.10	+0.16	−0.10	2/4
31	21F	RexoT, R hyper T, DVD	+0.30	+0.80	+0.54	3
32	48F	LexoT	+0.30	+0.30	+0.30	2
33	53F	RexoT, DVD	+0.30	+1.00	+1.00	2/3
34	30M	RexoT	+0.40	+1.00	+1.00	3
35	12M	LexoT	0.00	+0.20	+0.20	3
36	15F	RexoT	+0.50	+0.70	+0.50	4
37	29F	AesoT, DVD	0.00	0.00	+0.10	4

 Ages are in years. AesoT, alternating esotropia; DVD, dissociated vertical divergence; ResoT, right esotropia; RexoT, right exotropia; LesoT, left esotropia; LexoT, left exotropia; R hyper T, right hypertropia; R hypo T, right hypotropia; L hyper T, left hypertropia; L hypo T, left hypotropia; LogMAR, log minimum angle of resolution; RE, right eye; LE, left eye; PL, perception of light.

Figure 1.

 

The four types of MLN. During binocular viewing (top row) the eyes exhibit one of four states (left to right, respectively): stability (type 1 MLN), square-wave jerks (type 2 MLN), torsional nystagmus (type 3 MLN), or horizontal MLN (type 4 MLN). All four types show typical MLN during monocular viewing (bottom row) with the fast phase beating toward the viewing eye.

Figure 2.

 

A subject (S15) with type 2 MLN showing square-wave jerk oscillations during binocular viewing. Right-beating MLN or left-beating MLN were seen whenever either the right eye (RE) or the left eye (LE) viewed the target. Note that very occasionally during binocular viewing low-amplitude (<1°) left-beating MLN was seen. Positive and negative values represent rightward and leftward directions, respectively.

Figure 3.

 

A subject (S31) with type 3 MLN showing torsional nystagmus during binocular viewing. This oscillation then became either right-beating MLN or left-beating MLN whenever the right eye (RE) or left eye (LE) was viewing. The traces seen during left monocular viewing are genuine and do not show saturation. Values at left explained in Figure 2 .

Figure 4.

 

A subject (S21) with a type 4 MLN showing decreasing-velocity slow-phase nystagmus during both binocular and monocular viewing with the fast phase always beating toward the viewing eye. Values at left explained in Figure 2 .

Figure 5.

 

A subject (S30) displaying a type 2–4 MLN hybrid. Regular bursts of both square-wave jerks (SWJ) and decreasing-velocity slow phases (MLN) were present during binocular viewing. During monocular viewing, the MLN was either right-beating when the right eye (RE) was viewing or left-beating when the left eye (LE) was viewing. Values at left explained in Figure 2 .

Figure 6.

 

Distribution of the MLN types found in the subject group (n = 37).

Figure 7.

 

Six classes of MLN slow phases were identified: class I (A) decreasing velocity, slow phase; class I (B) saccade with a decreasing velocity slow phase; class II (A) linear slow phase; class II (B) saccade with a linear slow phase; Both class III (A) and class III (B) have strong pendular components to the slow phases.

Figure 8.

 

Incidences of different waveform classes seen in three subjects (S15 with type 2 MLN, left; S31 with type 3 MLN; middle; S20 with type 4 MLN, right). The MLN types are classified in Figure 1 , and the waveform variations are illustrated in Figure 7 . Note that no subject had one unique slow-phase class and that the distribution of the classes are independent of the MLN type each subject exhibited. SWJ, square-wave jerks; T, torsional nystagmus; 1A, 1B, 2A, 2B, 3A, 3B, six slow phase classes; CN, congenital nystagmus (increasing velocity slow phase).

Figure 9.

 

The effect of the presence of a target (left), the absence of a target (middle), and image stabilization (right; fbg +1.0) on MLN for subjects with types 2, 3, and 4 MLN during monocular viewing for the subjects described in Figure 8 . Removal of visual feedback decreased the slow-phase velocity and reduced the number of fast phases.

Figure 10.

 

The effect of visual feedback on the distribution of the different slow-phase classes in the three subjects described in Figure 8 . Feedback experiments were all performed during monocular viewing only.

Figure 11.

 

The six possible responses to the introduction of feedback (fbg) in subjects with MLN. (A) No change, (B) the oscillation reverts to square-wave jerks, (C) large-amplitude oscillations are exhibited, (D) a gaze shift is produced by saccades, (E) a gaze shift is produced by slow eye movements, and (F) intensity changes and slow eye position drifts.

Figure 12.

 

The effect of 4 different levels of feedback gain (fbg) on the change in eye position after the introduction of visual feedback in a subject with type 4 MLN.

Figure 13.

 

The effect of the removal of visual feedback on eye position (same patient as in Figure 12 ). Eye position changes were achieved through either an extended slow phase (A) and (B) or a saccade (C).

The authors thank Jon Whittle for his comments and Anne Bjerre for her assistance.