Ординатура / Офтальмология / Английские материалы / Advances in Understanding Mechanisms and Treatment of Infantile Forms of Nystagmus_Leigh, Devereaux_2008

In our recent studies, we have focused on the role of the cerebellar nodulus and uvula in pursuit and the translational vestibulo-ocular reflex (TVOR). Prior studies have implicated the nodulus and uvula in several other functions. First, they control angular velocity storage, which enhances the response to sustained and low-frequency head rotation or rotational optokinetic stimulation.15 Second, they are responsible for orienting the axis of eye velocity to the gravito-inertial axis.16,17 Third, they control the torsional vestibuloocular reflex.18 Some humans and animals with lesions to this part of the cerebellum develop the characteristic eye movement disorder of periodic alternating nystagmus (PAN), which responds well to baclofen.19

METHODS

We studied two rhesus monkeys (M1 and M2) before and after surgical aspiration of the cerebellar nodulus and uvula. Before the experiments described here, M1 had had a trochlear nerve section as part of a different study.20 All experimental procedures were approved by the Animal Care and Use Committee of the Johns Hopkins University. Eye movements were recorded using binocular scleral coils.

Pursuit Experiments

Animals sat in a primate chair with the head fixed. For pursuit experiments, the target consisted of a small red spot, generated by an LCD projector and backprojected onto a tangent screen that was 66 cm from the animal. There were two pursuit paradigms. For step-ramp pursuit, each trial began with fixation of a stationary center target. At a random time, the target stepped up or down by approximately 4° and then began to move at a constant speed of 20 deg/s in the opposite direction. The target continued to move for approximately 1 second after the eye started to move. Sinusoidal pursuit was elicited by a continuously moving target (0.3 Hz, peak velocity ±37.5 deg/s, amplitude ±20°) in either the vertical or horizontal direction. The animal was rewarded for maintaining fixation of the target.

Raw coil signals were converted to rotation vectors and angular velocity vectors, as has been previously described.21 For step-ramp pursuit, we calculated pursuit gain as the ratio of median eye velocity to target velocity during steady-state pursuit (t > 200 milliseconds from the onset of pursuit). For sinusoidal pursuit, the gain was determined by a least-squares linear regression of instantaneous eye velocity to target velocity; this regression was performed separately for each direction of motion.

TVOR Experiments

The horizontal TVOR was tested on a belt-driven linear sled. The monkey sat in the primate chair with head fixed. Each trial began with fixation of a laser target back-projected onto a screen that was placed either 70 cm or 27 cm from the monkey in a room that was otherwise dark. The chair moved abruptly along the interaural direction, accelerating at 400 cm/s2 (≈ 0.4 g) to a plateau speed of 40 cm/s. The total amplitude of the translation was 20 cm. Leftward and rightward trials were alternated. For each trial, the target either remained on during the motion or was extinguished when the chair started to move, with chair motion proceeding in complete darkness.

The vertical TVOR was studied using a manually driven, spring-assisted chair that was constrained to move vertically along metal support rods. The frequency of chair motion was approximately 1.5 Hz. Chair acceleration was measured by a linear accelerometer and integrated to determine chair velocity.

Lesions

Surgical lesions were performed by one of the authors (RT), using general inhalation anesthesia, standard aseptic neurosurgical technique, and postoperative analgesia. A suboccipital craniotomy was performed, the inferior vermis was visualized, and the nodulus and uvula were aspirated. The lesion site was verified by MRI and postmortem histology. M2 had the most complete lesion, with complete removal of the cortex of the Nod/Uv. In M1, some cortex was preserved, but the underlying white matter was disrupted, suggesting that the remaining cortex was functionally disconnected.

RESULTS

Animals tolerated the surgery well. They recovered quickly and had no sustained movement deficits. Neither of the animals had PAN, even in darkness.

Effect of Lesions on Pursuit

The main effect of the lesion was to reduce the gain of downward pursuit, elicited by either sinusoidal or stepramp stimuli. In fact, downward pursuit was largely abolished in M2, the animal with the more complete lesion (Fig. 7.1). This was true for both step-ramp and sinusoidal stimuli. Upward pursuit was less affected.

Figure 7.2 depicts average pursuit gains, before and after the lesions, for two monkeys. On average, the gain of downward pursuit decreased by 72% for

Figure 7.1 Vertical step-ramp pursuit before (top) and after (bottom) Nod/Uv lesions in M2. Downward pursuit was essentially abolished after the lesion (bottom left); only saccades are seen. Upward pursuit was less affected (bottom right), although the initial acceleration was reduced, resulting in larger catch-up saccades (arrow). Signs reflect the right-hand rule (downward is positive).

step-ramp and 59% for sinusoidal pursuit. There was a modest decrease in the gain of upward step-ramp pursuit (21%) and little effect on upward sinusoidal pursuit (4% increase). Horizontal step-ramp pursuit gains decreased by 20% (data not shown).

Effect of Lesions on the Interaural TVOR

We studied responses to brief steps of translation. The main effect of the lesions was to reduce the steady-state response to constant-velocity motion; there was little effect on the response during initial chair acceleration. To illustrate this, Figure 7.3 shows the response to interaural translation in M1. Note that the very early response (shaded area) was similar before and after the lesion, but that the eye velocity during the later portion of the response was much lower after the lesion. A similar effect was seen in M2.

The Nod/Uv lesions did not eliminate the normal scaling of eye velocity by target distance. When the distance to the fixation target was 27 cm (Fig. 7.3B) rather than 70 cm (Fig. 7.3A), the eye velocity was greater, particularly in the early (acceleration) portion of the response. This was true also for M2.

Effect of Lesions on the Vertical TVOR

We also determined the effect of the lesions on the response to sinusoidal vertical translation (bob). For technical reasons, the data for the vertical TVOR are more limited. Most notably, we did not have a display- and-reward setup that would allow for precise control of eye position and vergence angle. Instead, we simply recorded spontaneous responses in the light and in darkness. The most reliable responses were obtained in the light. The viewing distance was the same for recordings before and after the cerebellar lesions (122 cm). As shown in Figures 7.4 and 7.5, after the Nod/Uv lesions the response to vertical translation was reduced.

Unlike vertical pursuit, the magnitude of the effect was similar for upward and downward translation. There was no relative sparing of upward slow phases.

DISCUSSION

Our study provides important new information regarding the function of the Nod/Uv in the control of eye movements and maintaining gaze stability during selfand object-motion. Specifically, we have shown that lesions to the Nod/Uv impair downward pursuit, and, to a lesser degree, horizontal pursuit, while largely sparing upward pursuit. We also found a reduced response to vertical translation and an impaired ability to maintain horizontal eye velocity during constantvelocity translation along the interaural axis.

Pursuit

In our monkeys, lesions of the Nod/Uv caused a pattern of pursuit deficits that closely resemble common findings in patients with cerebellar ataxia, in whom downward pursuit is much more profoundly impaired than upward pursuit.22,23 Our finding supports an important role for the Nod/Uv in this pattern of vertical pursuit. In fact, in one monkey downward pursuit was abolished. However, the degree to which asymmetrical vertical pursuit is specific to lesions of the Nod/Uv is uncertain. For example, a prior study found that flocculectomy reduced, but did not abolish, vertical eye velocity during smooth tracking.24 Other factors, such as the visual environment, may also be important for vertical pursuit asymmetries. For example, Takeichi et al.25 reported asymmetric vertical pursuit in normal monkeys, but only in young monkeys, and only when

Figure 7.5 Vertical translational vestibulo-ocular reflex (TVOR) response sensitivities before and after Nod/Uv lesions. As in Figure 7.2, the symbols show the individual values for each monkey, and the bars show the means. In both animals, the sensitivities for upward and downward translation were reduced after the lesions.

pursuit was performed against a textured background. Under those conditions, upward rather than downward pursuit was impaired. We did not test pursuit against a textured background.

Finally, our findings differ from those of a prior study in which reversible chemical lesions of the cerebellar uvula led to an increase in the open-loop acceleration of horizontal pursuit26; the effect on vertical pursuit was not reported. Here we did not find an increased acceleration for either horizontal or vertical pursuit in our monkeys. This difference in our results may relate to the extent of the lesions. In our monkeys, both the nodulus and the uvula were involved.

TVOR

No prior studies have investigated the effects of discrete cerebellar lesions on the TVOR. It is known, however, that the cerebellum must play a central role in control of the TVOR, because humans with diffuse cerebellar disease often have dramatically reduced responses to interaural translation.27-29 On the other hand, the specific functions of individual cerebellar substructures are not known. Our results indicate that the Nod/Uv is most concerned with the maintenance of eye velocity during sustained linear motion; there was little effect of the lesions on initial eye acceleration. This suggests that the Nod/Uv may be part of an integrator of head acceleration signals provided by otolith inputs. Such a function would be analogous to the role of the nodulus in controlling velocity storage for the RVOR.

Our study is also the first to determine the role of the cerebellum in the vertical TVOR. We found that Nod/Uv lesions reduced both upward and downward slow phases during vertical translation in the light. Further study, under more precisely controlled viewing conditions, will be necessary to refine these results. From our data, it is difficult to compare the effects of the lesions on horizontal and vertical translation, as the head-motion stimuli were very different.

CONCLUSION

Our new findings—that the cerebellar nodulus and uvula have important functions in the generation of pursuit and of the TVOR—further emphasize the central role the cerebellum plays in the control of eye movements of all types. Our results also support several other general principles about the control of eye movements by the cerebellum: (a) reflexes subserving the needs of the fovea, such as pursuit and the TVOR, are particularly dependent on an intact cerebellum;

(b) the ancient vestibulocerebellum, which includes the nodulus and uvula, has assumed new functions that meet the needs of the more recent ocular motor systems that rely on the fovea and on visual inputs from the cerebral cortex; and (c) there is remarkable overlap of function in the cerebellar cortex, with different areas participating in the control of the same types of eye movements, and single areas participating in the control of multiple eye movement types. This redundancy and compartmentalization of function allows for compensation in the face of lesions in the cerebellum (or the areas that project to specific parts of it) as well as for interactions between the different eye movement subtypes.

ACKNOWLEDGMENTS This research was supported by National Institutes of Health grant EY001849 (DSZ), the Albert Pennick Fund, and the Arnold-Chiari Foundation. Dr. Walker was a Pollin scholar. Adrian G. Lasker and Dale C. Roberts provided technical assistance. The authors graciously acknowledge the support of Dr. Lloyd Minor, in whose laboratory experiments related to interaural translation were performed.

References

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ABSTRACT

Pathological nystagmus degrades vision because it introduces excessive image motion on the retina. Past studies have demonstrated that vision can be improved using electronic devices that move visual targets in lockstep with the oscillating line of sight. Such optomechanical visual-stabilization devices have multiple applications. They could be used to improve vision in patients whose nystagmus is resistant to other therapies. They could also be used to predict the degree of benefit a patient may expect to receive from a contemplated medical or surgical nystagmus-reducing therapy. A predictive tool is particularly important when the contemplated therapy involves significant expenses, risks, or discomforts. Visual stabilization devices can also be applied as research tools to explore the relationships between retinal image velocity, nystagmus waveforms, and oscillopsia. Selective image stabilization systems consist of an eye movement tracking device, a filtering system that extracts the pathological movement from the overall eye movement signal, and an optics or display mechanism (the “stabilizer plant”) that allows the seen world or displayed images to be oscillated synchronously with the extracted nystagmus signals. To date, optomechanical visual stabilization devices have been too complex to use outside the laboratory. In this chapter, we review our progress toward developing a self-contained optomechanical visual stabilization device suitable for use in the clinical setting. Although we focus on

the treatment of acquired pendular nystagmus, we also describe the application of this instrumentation to a patient with infantile nystagmus, illustrating how a computer-controlled stabilizer can serve as a research tool.

Pathological nystagmus degrades vision by introducing excessive motion of images across the retina. Nystagmus may also cause the unpleasant impression that objects are in motion (oscillopsia), particularly in the acquired forms of the disorder. Optical or optomechanical devices that artificially stabilize images on the moving retina can ameliorate the deleterious effects of acquired nystagmus on vision.1,2 The perceptual effects of stabilization devices have also been explored in patients with infantile nystagmus (IN).3,4 In most of these studies, the image stabilization was accomplished by projecting visual targets onto a tangent screen via mirror galvanometers and feeding the patients’ eye position signals to the galvanometers. Such arrangements are delicate, and their use is restricted to the experimental laboratory setting. In this chapter we review our efforts to develop an image stabilization system that nullifies the visual effects of nystagmus without interfering with normal eye movements, and that is both self-contained and sufficiently robust to be usable in clinical settings.

There are several applications for an electromechanical retinal image stabilization device (eRISD). First, the device could potentially be used to treat nystagmus. While many drugs have been reported to be helpful in small series of patients, in practice many patients experience no benefit or incomplete benefit,

or develop intolerable side effects such as sedation or ataxia.5-7 For instance, in a controlled study of the drug gabapentin in acquired pendular nystagmus (APN), 10 out of 15 patients experienced some improvement in acuity or nystagmus velocities, but only 8 of those elected to continue taking the drug.5 Thus one use of a small and user-friendly eRISD would be as a visual aid for patients with intractable nystagmus. Second, an eRISD could be used to assess a patient’s potential to benefit from nystagmus treatment. This application is particularly important in patients whose nystagmus is accompanied by abnormalities of the afferent visual system, as is commonly the case in patients who develop nystagmus due to multiple sclerosis or who have a symptomatic (i.e., nonidiopathic) form of IN. These afferent visual lesions may limit the degree to which vision can be improved by attenuating the nystagmus, and they may create an unfavorable risk-benefit ratio for some nystagmus treatments. Recent reports state that patients with acquired nystagmus can benefit from extraocular muscle surgery.8,9 The existence of an invasive therapy for nystagmus—with the attendant discomforts, costs, and risks—has increased the importance of having a way to predict whether a treatment will produce functionally meaningful benefits. Finally, an eRISD can be used as a tool to study nystagmus, for

instance, to investigate the impact of altering retinal image motion on the nystagmus waveform.

Figure 8.1 shows the basic schematic of an eRISD. It consists of some form of noninvasive eye tracker (e.g., one based on electro-oculography, video-oculog- raphy, or infrared reflectance technologies); a motionprocessing circuit that conditions, scales, or extracts the pathological feature(s) of the eye motion to be nullified; and image-shifting optics (the “stabilization plant”). An optical stabilization plant might be replaced by a computer screen attached to a computer that has been programmed to oscillate its video display. In this review, as in our work, we concentrate on the motion processor and stabilization plant, since eye trackers are already widely available. It should be recognized, however, that current commercial offerings do not possess the ideal characteristics for this application. For the purposes of use in a clinical eRISD, the ideal eye tracker would possess the following three features:

(1)electronics that are entirely contained in a small box (i.e., would not require a personal computer);

(2)self-starting and self-adjusting capacity upon activation, and (3) battery-power capability. A sampling rate of 60 Hz would be sufficient to nullify most forms of IN or APN, since the dominant frequencies of these movements are usually well below 10 Hz.10,11 However, the

propagation delay of slower oculography systems can be problematic. For instance, one commercially available 60 Hz video-oculography system introduces, on average, 33 milliseconds between the occurrence of an eye movement and the appearance of the signal at the system’s analog output. In a patient with a 4 Hz pendular nystagmus, this 33-millisecond delay would introduce a 48º lag between the eye movement and the corrective motion of the eRISD, substantially reducing the stabilization effect. In the case of a purely pendular nystagmus, a phase-shifting circuit/algorithm can be used to correct the phase relationship,12 but for forms of nystagmus with less predictable waveforms, a tracker with a propagation delay well below 10 milliseconds would be necessary. Since no commercial oculography system possesses all the ideal characteristics enumerated here, there is room for development of the tracker component of the eRISD, as well.

THE STABILIZATION PLANT

Table 8.1 summarizes the advantages and disadvantages of a variety of stabilization plants. A computer that is programmed to oscillate its video display is a particularly simple and attractive solution, as it would obviate the need for expensive and delicate optomechanical components. Its disadvantage is that it could only be used to view computer screens. However, for a neurological patient whose activities are constrained by other neurological deficits, the ability to see a computer screen may be enormously important. The significance of the limitation has waned in recent years, as the uses of personal computers to enhance daily life have exploded. The concept of the oscillating computer screen could be extended somewhat by placing a miniature computer screen in a head-mounted arrangement along with a forward-directed video camera (a “virtual reality display”). With this arrangement, the patient’s view of the outside world could be

stabilized. The latter arrangement shares the advantages of the oscillating computer screen and adds the virtues of portability and the ability to stabilize vision during activities other than computer use. Two disadvantages of this arrangement are the patient’s indirect view of the world through a television camera and the necessity of inconvenient camera adjustments in order to obtain clear images of finely detailed objects (e.g., a printed page).

A beam-steering mirror can be thought of as the next level of complexity. Beam-steering mirrors capable of deflecting the image in two dimensions can be purchased as commercial items. They can be constructed to generate large amplitudes of deflection, creating the ability to stabilize large-amplitude nystagmus waveforms. The beam-steering mirror would be mounted with a second mirror so as to produce a forward-viewing, periscope-like device. The chief disadvantage of this form of stabilization plant is that a steering device capable of moderate deflection amplitudes (≈ ±5°) and shrouded so as to prevent contact with the delicate first-surface mirrors would likely be quite bulky. The final entry in Table 8.1, “beamsteering lens,” has advantages over mirror arrangements in that it would afford the patient a straight-line (i.e., nonperiscopic) view of the visual world, and the optical housing would likely be more compact. The chief disadvantage of this approach is the greater mechanical complexity of the apparatus. Our own work has concentrated on this type of apparatus.

THE MOTION PROCESSOR

The motion processor could be as simple as a circuit that scales the amplitude of the eye movement signal to render it appropriate as a driving signal for the stabilization plant. A major disadvantage of such a “direct drive” approach is that it would nullify normal reflexive and voluntary eye movements to the same extent

Time (s)

acceleration and disable image stabilization until the saccade had terminated. VOR might be preserved by monitoring head velocity and subtracting it from the eye-velocity signal being fed to the stabilization plant. An alternative to this “rejection filter” strategy is an “acceptance filter” motion processor that identifies the nystagmus waveform and passes only that signal to the stabilization plant. Acceptance filters are a particularly good choice when the nystagmus waveform is highly deterministic (as is the case in APN), as they avoid the difficulty inherent in the rejection filter’s having to recognize each type of desired eye movement. Since our work has focused on developing a visual aid for APN, we have focused on the acceptance filter strategy.

Figure 8.2 Fixation instability engendered when a normal subject views through an electronic retinal image stabilization device (eRISD) set to completely nullify eye movements. A voluntary rightward saccade initiates repeated horizontal eye movements.

that it nullified the nystagmus. For this reason, the passive optical image stabilization device consisting of a negative-power contact lens and a positive-power spectacle (which replicates a direct-drive eRISD) caused oscillopsia in patients during head movements, due to its nullifying effect on the vestibulo-ocular reflex (VOR).13 A less familiar consequence of direct drive is that it produces an open-loop condition during smooth pursuit and voluntary saccades. Figure 8.2 illustrates this point, showing the horizontal eye position in a normal subject using an image stabilization device adjusted for a nullification gain of 1.0 (device nullified 100% of any eye movement). At the beginning of the record, the subject attempted a small rightward saccade to fixate a target approximately 1° to the right of the initial fixation point. The device displaced the target further to the right, initiating a staircase of rightward saccades as the subject made a futile attempt to “catch” the target. An attempt to pursue a moving target would have generated an exponentially increasing smooth pursuit velocity, driving the image stabilizer to its deflection limit.

An important advantage of an eRISD over a passive optical stabilizing device2,13,14 is that the device can be designed to nullify the nystagmus without interfering with normal eye movements. There are two basic strategies by which selective nullification can be achieved. In the first strategy, the motion processor is designed to recognize normal eye movements and block them from reaching the stabilization plant. For instance, the processor could recognize saccades by their high

FIRST-GENERATION DEVICE

Our first eRISD was designed as a table-mounted, analog electronic device.12 Horizontal and vertical eye movements were sensed using a battery-pow- ered infrared reflectance system. The stabilization plant consisted of a Risley prism driven by a stepper motor. Acceptance filter motion processing was accomplished using a phase-locked loop (PLL) circuit. The output of the PLL’s voltage-controlled oscillator was a fixed-amplitude sine wave, the phase and frequency of which would match the sinusoidal pendular nystagmus. This output was fed to the Risley prism motor control circuit after passing through additional circuitry that allowed the experimenter to adjust the amplitude of the motion of the stabilization plant, as well as to optimize the phase relationship between the nystagmus and the stabilization plant. The circuit also incorporated aspects of a rejection-type filter, in that the effects of large saccades on the PLL were ameliorated by a sample-and-hold circuit that, when triggered by a high eye acceleration, maintained the presaccadic velocity signal until the saccade terminated. Although the device was capable of nullifying both vertical and horizontal oscillations simultaneously, in practice we restricted our stabilization to the axis with the larger oscillation amplitude.

We tested the effects of this eRISD on monocular acuity in 5 patients with APN due to multiple sclerosis. In each patient we selected one eye and axis of correction (vertical or horizontal), seeking to study the eye in which acuity was least affected by optic nerve damage (due to previous episodes of optic neuritis) and in which the oscillations were most pronounced, most sinusoidal, and closest to pure vertical or horizontal. We assessed acuity using Landolt C optotypes, either presented on cards or displayed as a timed slideshow on a laptop computer. For each optotype size, we scored the number of correct responses, constructed a curve

of fraction correct versus optotype size, and fit the curve with a sigmoid. We defined acuity as the optotype size at which the fitted curve fell midway between perfect and chance performance. Four of five patients experienced an improvement in acuity of at least 0.05 LogMAR. The average increase in LogMAR acuity of the 5 patients was 0.17. This initial work supported the feasibility of an eRISD that could nullify nystagmus selectively and could potentially operate outside the setting of the experimental ocular motor physiology laboratory.

The first-generation device had a number of important deficiencies. Chief among these deficiencies was the fact that the PLL filter was unable to adjust automatically for moment-to-moment fluctuations in nystagmus amplitude. The PLL also required several cycles of nystagmus to achieve lock, reducing the percentage of time that the device was actually improving retinal-image stability. The fidelity of the stabilization plant was also fairly poor (owing in part to mechanical backlash in the prism gearing), resulting in prominent ripples in the retinal-image motion that were appreciated by users as a high-frequency jitter of the optotypes.

SECOND-GENERATION DEVICE

Our second eRISD was designed as a head-mounted device with computerized motion processing.15,16 Horizontal and vertical eye movements were sensed using a video-oculography system. The stabilization plant consisted of a three-lens assembly in which the center, biconcave lens was oscillated perpendicularly to the optical axis by electromagnets. This type of image-stabilizing optics is used by Canon Inc. (Tokyo, Japan) for their line of image-stabilizing lenses, and we actually obtained the biconcave lens, lens support, electromagnets, and targets for optical feedback sensors by disassembling one of these commercial lenses. We incorporated these elements, together with our own fixed lenses, optical feedback components, and the ultra-miniature television camera of the videooculography system, into an adjustable head mount. Digital motion-control software was created in RealTime Simulink (MathWorks, Natick, MA) running on a desktop computer. The heart of the motion-process- ing software was an adaptive interference cancellation filter.17 This filter generated sine waves, the amplitude and phase of which matched that of the horizontal and vertical components of the nystagmus waveform. This algorithm is the equivalent of an analog notch filter, with the center frequency and selectivity determined, respectively, by the frequency of a pair of internal sine wave generators and a constant, , which governs the rate at which the filter adapts. A separate program

block, containing a Fourier transform, was used to match the frequency for the internal sine wave generators to that of the nystagmus.

Because the ability of an eRISD to improve acuity in patients was already well established, and because our larger goals (which included evaluation of other strategies to improve vision, not discussed here) required multiple lengthy recording sessions, we chose to test this new eRISD using normal subjects in whom the visual effects of nystagmus were simulated by oscillating the visual display. Using normal subjects at this stage also circumvented one of the confounds of working with actual patients with multiple sclerosis: acuity may be significantly limited by causes other than nystagmus. In our first set of experiments (conducted before the new stabilization plant had been constructed), we also simulated the effects of an image stabilization plant with perfect fidelity, by driving the display oscillation by the difference between the nystagmus waveform (either a recorded patient waveform or the output of a function generator) and the output of the motion processor.15 In a later set of experiments (conducted after the new stabilization plant became available), the display was driven directly by the function generator, and the motion-processing optics were fed the sum of the function generator’s signal and the subject’s own eye movement signals,16 as depicted in Figure 8.1. In this way we were able to test the response of the filter to a realistic eye movement signal containing both normal eye movements and a pendular component. Acuity was determined in a fashion similar to our tests of the first-generation system.12 Eight-position Landolt C optotypes embedded in distraction optotypes were displayed on a computer screen in timed fashion, the percentage of correct responses was recorded, sigmoid curves were fit to the plots of percentage correct versus optotype size, and acuity was defined as the midpoint between perfect and chance performance. In our experiment with the actual (not simulated) stabilization plant,16 acuity was determined with the optotypes and stabilizer stationary (baseline condition), with the optotypes in motion and the device disabled (untreated condition), and with the optotypes in motion and the eRISD operating (treated condition). No subject was able to identify any of the largest optotypes in the untreated condition, while in the treated condition acuity was restored, on average, to approximately one line of the baseline value on a Bailey-Lovie LogMAR acuity chart.

The second-generation system represented an important step forward, as it demonstrated the feasibility of a head-mounted stabilization plant and selective nullification of the nystagmus using computer-based motion processing. Fidelity, size, and power consumption were tremendously improved over the original