A novel and inexpensive digital system for eye movement recordings using magnetic scleral search coils.

After their introduction by Robinson (IEEE Trans Biomed Eng 10:137-145, 1963), magnetic scleral search coils quickly became an accepted standard for precise eye movement recordings. While other techniques such as video-oculography or electro-oculography may be more suitable for routine applications, search coils still provide the best low-noise and low-drift characteristics paired with the highest temporal and spatial resolution. The problem with search coils is that many research laboratories still have their large and expensive coil systems installed and are acquiring eye movement data with old, analog technology. Typically, the number of recording channels is limited and modifications to an existing search coil system can be difficult. We propose a system that allows to retro-fit an existing analog search coil system to become a digital recording system. The system includes digital data acquisition boards and a reference coil as the hardware part, receiver software, and a new calibration method. The circuit design has been kept simple and robust, and the proposed software calibration allows the calibration of a single coil within a few seconds.

A novel method of 3D image analysis of high-resolution cone beam CT and multi slice CT for the detection of semicircular canal dehiscence.

HYPOTHESIS: We investigated if current-generation computed tomographic (CT) scanners have the resolution required to objectively detect bone structure defects as small as 0.1 mm. In addition, we propose that our method is able to predict a possible dehiscence in a semicircular canal. BACKGROUND: In semicircular canal dehiscence (SCD), the bone overlying the superior canal (SC) is partially absent, causing vertigo, autophony, hyperacusis or hearing loss. Diagnosis of SCD is typically based on multi-slice computed tomography (MSCT) images combined with the consideration of clinical signs and symptoms. Recent studies have shown that MSCT tends to overestimate the size of dehiscences and may skew the diagnosis towards dehiscence when a thin bone layer remains. Evaluations of CT scans for clinical application are typically observer based. METHODS: We developed a method of objectively evaluating the resolution of CT scanners. We did this for 2 types of computed tomography: MSCT, and cone beam computed tomography (CBCT), which have been reported to have a higher resolution for temporal bone scans. For the evaluation and comparison of image accuracy between different CT scanners and protocols, we built a bone cement phantom containing small, well-defined structural defects (diameter, 0.1-0.4 mm). These small inhomogeneities could reliably be detected by comparing the variances of radiodensities of a region of interest (i.e., a region containing a hole) with a homogenous region. The Fligner-Killeen test was used to predict the presence or absence of a hole (p ≥ 0.05). For our second goal, that is, to see how this technique could be applied to the detection of a possible dehiscence in a SC, a cadaveric head specimen was used to create an anatomic model for a borderline SCD; the SC was drilled to the point of translucency. After semi-automatically fitting the location of the canal, our variance-based approach allowed a clear, significant detection of the thin remaining bone layer. RESULTS: Our approach of statistical noise analysis on bone cement phantoms allowed us to distinguish real irregularities from measured image noise or reconstruction errors. We have shown that with computed tomography, an approach comparing radiodensity variance in regions of interest is capable of detecting inhomogeneities down to 0.1 mm (p ≤ 0.0001). CONCLUSION: Our analysis of data from the cadaveric head specimen demonstrates that this approach can be used to objectively detect thin layers of bone overlying an SC. This should provide the basis for using this approach for a semi-automated, objective detection of SCD.

Introducing a new parameter for the assessment of the tear film lipid layer.

PURPOSE: The differential diagnosis of dry eye syndrome is still a challenging task. The purpose of this study was to understand the relationship between a novel, objective clinical parameter, the "corrected lipid layer stabilization time," and commonly performed clinical tests for dry eye patients. METHODS: Data were obtained from a prospective clinical study with 59 patients of different subjective severity, as determined with the Ocular Surface Disease Index (OSDI). The dynamics of the tear film lipid layer were made visible through a white light source and were stored digitally. Because the distance between the upper and lower eyelid affects the lipid layer dynamics and varies significantly between subjects, the distance of the eyelids was determined and used to correct the lipid layer stabilization time. The resulting parameter was compared with common clinical procedures. RESULTS: The corrected lipid layer stabilization time has a highly significant correlation with tear film breakup time (Spearman r = -0.485, P < 0.01), Schirmer test without anesthesia (r = -0.431, P < 0.01) and with the Ocular Surface Disease Index (r = 0.498, P < 0.01). It also correlates with the lissamine green staining score (r = 0.379, P < 0.05), but shows no correlation with the osmolarity of the tear film. Without the correction for the eyelid opening, the correlations decrease considerably. CONCLUSIONS: These data suggest that the diagnostic value of the lipid layer stabilization time for the assessment of the severity of dry eye syndrome increases considerably when it is corrected by the distance of the eyelids.

Sustained effects for training of smooth pursuit plasticity.

Maintaining orientation in space is a multisensory process, with the vestibular, visual, auditory and somatosensory systems as inputs. Since the input from each individual system changes, for example due to aging, the central nervous system must continuously adapt to these changes to maintain proper system performance. Changes can also be elicited by targeted modifications of the inputs, or by controlled training of sensory systems. While the effects of adaptation on eye movements elicited by the vestibulo-ocular reflex are well established, modifications of the efficacy of smooth pursuit eye movements are less well understood. We have investigated whether two 6-min training sessions on three subsequent days can induce lasting changes in the open- and closed-loop smooth pursuit performance of healthy, adult subjects. Ten subjects practiced making pursuit eye movements by tracking a target cross which moved quasi-randomly on a computer screen. Smooth pursuit performance was tested with a step-ramp paradigm immediately before and after the training, as well as 5 days after the last training session. Our results show that even such short training sessions can induce significant, lasting improvements in closed-loop smooth pursuit performance if the pursuit system of the subjects is challenged sufficiently during training. Control experiments on ten additional adult subjects who had their pursuit performance tested before and after a 20 min break without visual training confirmed that the pursuit enhancement is due to the visual training and not due to perceptual learning.

Biomechanical analysis of x-pattern exotropia.

PURPOSE: To simulate and check the plausibility of the proposed mechanisms of X-pattern exotropia and to determine the least invasive surgical method that can be used to treat the disorder. DESIGN: Computational supported analysis and retrospective study. METHODS: The oculomotor model SEE++ was used to simulate the effects of the different causes that have been proposed for the X-phenomenon. In addition, a retrospective study was conducted using preoperative and postoperative measurements of 10 patients with X-pattern exotropia. Eye movements and surgery of these patients were simulated and analyzed statistically. RESULTS: Our computer-based simulations showed that only 1 of the 4 proposed theories can account successfully for the observed X-patterns: an overaction of all 4 oblique muscles can induce divergent exotropia in upgaze and downgaze, and an alteration of horizontal muscles can cause the additional divergence in all gaze positions. The simulation of eye muscle surgery confirmed that a sufficient correction of the divergent deviation in all gazes already can be achieved by a recession and resection of 2 horizontal eye muscles. CONCLUSIONS: In case of X-pattern exotropia, recession and resection of 2 horizontal muscles can be used as a first-line therapy, leading to a simplification of the therapy.

Results of electrocochleography in Ménière's disease after successful vertigo control by single intratympanic gentamicin injection.

In the last several years, a promising new approach has been suggested in the therapy of Ménière's disease (MD): the low-dose intratympanic gentamicin therapy. By titrating the desired vestibular inhibition by single injections and infrequent administration, side effects concerning hearing can be held on an acceptably low level, while disease-related symptoms are often successfully eliminated. However, it is still unclear if endolymphatic hydrops actually decreases when the patients become symptom free. In the literature, hydrops is significantly associated with an enhanced ratio of summating potential/action potential (SP/AP). Our aim in this retrospective study was to answer the question if pathologically high SP/AP ratios normalize after successful low-dose intratympanic gentamicin treatment. Twenty-eight patients with MD received one, two or three intratympanic gentamicin injections. These injections inhibited vertigo spells without causing additional hearing loss. SP/AP ratios measured by noninvasive electrocochleography did not improve statistically when patients became symptom free. This indicates that the beneficial effect of gentamicin does not depend on the improvement of SP/AP ratios. Considering the well-established correlation between increased SP/AP and active MD, it thus seems unlikely that gentamicin treatment significantly reduces hydrops.

Measuring torsional eye movements by tracking stable iris features.

We propose a new method to measure torsional eye movements from videos taken of the eye. In this method, we track iris features that have been identified as Maximally Stable Volumes. These features, which are stable over time, are dark regions with bright borders that are steep in intensity. The advantage of Maximally Stable Volumes is that they are robust to nonuniform illumination and to large changes in eye and camera position. The method performs well even when the iris is partially occluded by reflections or eyelids, and is faster than cross-correlation. In addition, it is possible to use the method on videos of macaque eyes taken in the infrared, where the iris appears almost featureless.

Applying knowledge--challenges in bringing scientific advances to dizzy patients.

Simple diagnostic or therapeutic procedures can produce tremendous benefits for dizzy patients. To see how new ideas in the laboratory evolve into benefits for patients, an attempt to analyze how the corresponding information is distributed was made. To quantify that flow of information, a number of new scientific publications, citation numbers, and a number of new books on relevant subjects were looked at. For vertigo, this approach was facilitated by the fact that the diagnostic procedures for benign paroxysmal positioning vertigo (BPPV) and for canal paresis can be traced back to seminal publications. Results indicate that the current way of disseminating new information used here is working well, and that new ideas on diagnosis and treatment are readily available to practitioners. However, the application of new methods is limited by the availability of the required technology. It is conjectured that the technological requirements have become more complex over time, leading to a slower uptake of new technology.

Computer-assisted dosage calculation for strabismus therapy in myopic patients.

PURPOSE: The published dosage recommendations for the surgical correction of horizontal strabismus in non-myopic patients show large, unexplained differences. For patients with high myopia, the situation becomes even more complex because the increase in the size of the bulb also affects the geometry of the oculomotor muscles. In this study, we wanted to investigate whether computer simulations of the oculomotor plant can be used to find accurate surgical parameters. METHODS: In a retrospective study, we investigated pre- and postoperative strabismus patterns in 13 patients affected by convergent (seven patients) or divergent (six patients) strabismus and high myopia. Postoperative checks were made 1 day, 1 week, 3 months and 1-6 years after the operation. For each patient, we simulated the presurgical strabismus pattern with SEE++ (see 'Further Information' for manufacturer details), a biomechanical simulation program of the oculomotor plant. The individual results of the simulations were then compared to the measured postoperative strabismus patterns. RESULTS: We found a trend of under-correction in the postoperative situation, resulting in four patients having a large remaining strabismus angle of more than 5 degrees. The computer simulations were able to reproduce this under-correction, and suggested an increase in dosage. CONCLUSION: We conclude that realistic biomechanical simulations of the oculomotor plant can predict the postoperative result for myopic patients accurately. The results of the computer simulation correlate well with the postoperative outcome of the patient.

The orientation of Listing's Plane in microgravity.

The orientation of Listing's Plane (LP) was examined under one-g and zero-g conditions during parabolic flight. Ten healthy subjects participated in the experiment. In zero-g the orientation of LP was consistently altered. LP elevation was tilted backwards by approx. 10 degrees (p=0.003). The azimuth angles of the left and right eyes also diverged in zero-g, with a statistically significant change (p=0.04) in the vergence angle between 6.1 degrees and 11.8 degrees . A discernible dissociation in torsional eye position was also observed, which proved to be statistically significant (p=0.03). The thickness of LP was found to be of the order of 1 degrees , and was not significantly altered by the transitions between one-g and zero-g. Additional control experiments involving repeated measurements of LP under normal laboratory conditions demonstrated that the parameters of LP remain stable in the individual. The parabolic flight results demonstrate that in contrast to re-orientation in the one-g gravitational field, the elimination of gravity represents a qualitative change for the vestibular and oculomotor systems. It appears that given the lack of voluntary control of ocular torsion, the tonic otolith afferences are instrumental in the stabilisation of torsional eye position and consequently of Listing's Plane. The observed torsional divergence also provides support for the so-called otolith asymmetry hypothesis.

Vestibular contribution to the planning of reach trajectories.

Reaching for an object while simultaneously rotating induces Coriolis and centrifugal inertial forces on the arm that require compensatory actions to maintain accuracy. We investigated whether the nervous system uses vestibular signals of head rotation to predict inertial forces. Human subjects reached in darkness to a remembered target 33 cm distant. Subjects were stationary, but experienced a strong vestibular rotation signal. We achieved this by rotating subjects at 360 degrees /s in yaw for 2 min and then stopping, and subjects reached during the 'post-rotary' period when the deceleration is interpreted by the vestibular system as a rotation in the opposite direction. Arm trajectories were straight in control trials without a rotary stimulus. With vestibular stimulation, trajectory curvature increased an average of 3 cm in the direction of the vestibular stimulation (e.g., to the right for a rightward yaw stimulus). Vestibular-induced curvature returned rapidly to normal, with an average time constant of 6 s. Movements also became longer as the vestibular stimulus diminished, and returned towards normal length with an average time constant of 5.6 s. In a second experiment we compared reaching with preferred and non-preferred hands, and found that they were similarly affected by vestibular stimulation. The reach curvatures were in the expected direction if the nervous system anticipated and attempted to counteract the presence of Coriolis forces based on the vestibular signals. Similarly, the shorter reaches may have occurred because the nervous system was attempting to compensate for an expected centrifugal force. Since vestibular stimulation also alters the perceived location of targets, vestibular signals probably influence all stages of the sensorimotor pathway transforming the desired goal of a reach into specific motor-unit innervation.

A comparison of two different techniques for oculomotor torque reduction.

PURPOSE: To compare the results of two different surgical techniques: 'Cüppers technique', in which the torque of oculomotor rectus muscles is reduced by suturing the muscle to the globe in the posterior half of the globe; and 'Y-split recessions', in which the muscle torque is reduced by Y-splitting the rectus muscles, and reattaching the two halves at an angle to each other. METHODS: We carried out a retrospective analysis of the outcome of surgery on 100 patients with infantile esotropia. RESULTS: Both techniques show a sufficient reduction of strabismus angle variability, and minimal and maximal strabismus angle. CONCLUSIONS: Both techniques achieve satisfactory results. In addition, the Y-split technique allows for accurate control of the muscle torque and requires no access to the posterior half of the eye, which can facilitate the surgical approach. For a reduction in muscle torque, the Y-split recession is a good alternative to the established Cüppers technique.

Model-based improvements in the treatment of patients with strabismus and axial high myopia.

PURPOSE: Eye motility disorders with axial high myopia and an enlarged globe are often characterized by a hypotropia of the affected eye, usually referred to as heavy-eye syndrome. Based on an intuitive interpretation of magnetic resonance (MR) images, the cause of the hypotropia has typically been assigned to the rectus muscles. In this study, the hypothesis that the oblique muscles play an important role in the underlying biomechanical disorder of this type of strabismus was investigated. METHODS: The hypothesis was tested by (1) a retrospective analysis of surgical results in one patient with unilateral axial high myopia; and (2) MR images of orbital tissues in two further patients with unilateral axial high myopia. RESULTS: MR images demonstrated a pattern of extraocular muscle path displacements similar to those described previously, but also a uniform decrease in the cross-sectional area of the inferior oblique muscles. Computer modeling required decreased inferior oblique contractility in addition to displaced extraocular muscle paths to recreate the observed motility pattern accurately. CONCLUSIONS: Patients with axial high myopia regularly show a reduction in the diameter of the inferior oblique. The resultant reduction in muscle-strength is important for the correct explanation of this complex eye movement disorder.

Angular vestibulo-ocular reflex gains correlate with vertigo control after intratympanic gentamicin treatment for Meniere's disease.

OBJECTIVES: The objective of our study was to determine whether angular vestibulo-ocular reflex (aVOR) gains correlated with vertigo control after intratympanic gentamicin treatment for Meniere's disease. METHODS: We conducted a prospective study of 18 subjects with unilateral Meniere's disease treated with intratympanic gentamicin injection and followed all subjects for 1 year. We measured the gain of the aVOR elicited by rapid rotary head thrusts in each of the canal planes for each subject before and after treatment with intratympanic gentamicin by using magnetic search coils to record eye movements. RESULTS: During the follow-up period, 11 subjects ("single-treatment group"; 61%) had control of their vertigo with a single gentamicin injection. The remaining 7 subjects ("multiple-treatment group"; 39%) experienced recurrent vertigo that required a second injection of gentamicin at a mean of 6 months after the first treatment. The 11 subjects in the single-treatment group had significantly greater reduction of labyrinthine function after the first treatment, as measured by change in ipsilateral horizontal canal gain, than did the 7 subjects with vertigo recurrence. Changes in caloric asymmetry did not correlate with vertigo control. CONCLUSIONS: Our results suggest that successful treatment of Meniere's disease is closely related to attenuation of semicircular canal function as measured by horizontal canal aVOR gains.

Human 3-D aVOR with and without otolith stimulation.

We describe in detail the frequency response of the human three-dimensional angular vestibulo-ocular response (3-D aVOR) over a frequency range of 0.05-1 Hz. Gain and phase of the human aVOR were determined for passive head rotations in the dark, with the rotation axis either aligned with or perpendicular to the direction of gravity (earth-vertical or earth-horizontal). In the latter case, the oscillations dynamically stimulated both the otolith organs and the semi-circular canals. We conducted experiments in pitch and yaw, and compared the results with previously-published roll data. Regardless of the axis of rotation and the orientation of the subject, the gain in aVOR increased with frequency to about 0.3 Hz, and was approximately constant from 0.3 to 1 Hz. The aVOR gain during pitch and yaw rotations was larger than during roll rotations. Otolith and canal cues combined differently depending upon the axis of rotation: for torsional and pitch rotations, aVOR gain was higher with otolith input; for yaw rotations the aVOR was not affected by otolith stimulation. There was a phase lead in all three dimensions for frequencies below 0.3 Hz when only the canals were stimulated. For roll and pitch rotations this phase lead vanished with dynamic otolith stimulation. In contrast, the horizontal phase showed no improvement with additional otolith input during yaw rotations. The lack of a significant otolith contribution to the yaw aVOR was observed when subjects were supine, prone or lying on their sides. Our results confirm studies with less-natural stimuli (off-vertical axis rotation) that the otoliths contribute a head-rotation signal to the aVOR. However, the magnitude of the contribution depends on the axis of rotation, with the gain in otolith-canal cross-coupling being smallest for yaw axis rotations. This could be because, in humans, typical yaw head movements will stimulate the otoliths to a much lesser extent then typical pitch and roll head movements.

Enhanced smooth pursuit eye movements in patients with bilateral vestibular deficits.

Patients with bilateral vestibular deficits experience unsteady gait and oscillopsia that can reduce the quality of life, though many patients adapt remarkably well and lead mostly normal lives. One source of adaptation could be the ability of sensory-motor systems to compensate for the vestibular loss by adaptive enhancement of their performance. We studied smooth-pursuit eye movements in five patients and six healthy control subjects using a step-ramp paradigm. Eye movements were measured with scleral search coils. Patients showed open- and closed-loop pursuit gains that were about 9% higher than controls. We suggest that the challenge of living with a deficient vestibular system caused an enhancement in the pursuit system, which contributes to the patient's overall compensation.

Improving calibration of 3-D video oculography systems.

Eye movement recordings with video-based techniques have become very popular, as long as they are restricted to the horizontal and vertical movements of the eye. Reliable measurement of the torsional component of eye movements, which is especially important in the diagnosis and investigation of pathologies, has remained a coveted goal. One of the main reasons is unresolved technical difficulties in the analysis of video-based images of the eye. Based on simulations, we present solutions to two of the primary problems: a robust and reliable calibration of horizontal and vertical eye movement recordings, and the extraction of suitable iris patterns for the determination of the torsional eye position component.

Ocular rotation axes during dynamic Bielschowsky head-tilt testing in unilateral trochlear nerve palsy.

PURPOSE: To explain the positive Bielschowsky head-tilt (BHT) sign in unilateral trochlear nerve palsy (uTNP) by the kinematics of three-dimensional eye rotations. METHODS: Twelve patients with uTNP monocularly fixed on targets on a Hess screen were oscillated (+/- 35 degrees, 0.3 Hz) about the roll axis on a motorized turntable (dynamic BHT). Three-dimensional eye movements were recorded with dual search coils. Normal data were collected from 11 healthy subjects. RESULTS: The rotation axis of the viewing paretic or unaffected eye was nearly parallel to the line of sight. The rotation axis of the covered fellow eye, however, was tilted inward relative to the other axis. This convergence of axes increased with gaze toward the unaffected side. Over entire cycles of head roll, the rotation axis of either eye remained relatively stable in both the viewing and covered conditions. CONCLUSIONS: In patients with uTNP, circular gaze trajectories of the covered paretic or unaffected eye during dynamic BHT are a direct consequence of the nasal deviation of the rotation axis from the line of sight. This, in turn, is a geometrical result of decreased force by the superior oblique muscle (SO) of the covered paretic eye or, according to Hering's law, increased force parallel to the paretic SO in the covered unaffected eye. The horizontal incomitance of rotation axes along horizontal eye positions can be explained by the same mechanism.

Incomitance of ocular rotation axes in trochlear nerve palsy.

Strabismus due to palsy of a single muscle in one eye is always incomitant, which is a consequence of Hering's law of equal innervation. We asked whether this law had similar consequences on the orientation of ocular rotation axes. Patients with unilateral trochlear nerve palsy were oscillated about the nasooccipital (= roll) axis (+/-35 degrees, 0.3 Hz), and monocularly fixed on targets on a head-fixed Hess screen. Both the covered and uncovered eyes were measured with dual search coils. The rotation axis of the covered eye (paretic or healthy) tilted more nasally from the line of sight when gaze was directed toward the side of the healthy eye. The rotation axis of the viewing eye (paretic or healthy), however, remained roughly aligned with the line of sight. We conclude that incomitance due to eye muscle palsy extends to ocular rotation axes during vestibular stimulation.

Dependence of adaptation of the human vertical angular vestibulo-ocular reflex on gravity.

We determined the spatial dependence of adaptive gain changes of the vertical angular vestibulo-ocular reflex (aVOR) on gravity in five human subjects. The gain was decreased for 1 h by sinusoidal oscillation in pitch about a spatial vertical axis in a subject-stationary surround with the head oriented left-side down. Gains were tested by sinusoidal oscillation about a spatial vertical axis while subjects were tilted in 15 degrees increments from left- to right-side down positions through the upright. Changes in gain of the vertical component of the induced eye movements were expressed as a percentage of the preadapted values for the final analysis. Vertical aVOR gain changes were maximal in the position in which the gain had been adapted and declined progressively as subjects were moved from this position. Gain changes were plotted as a function of head orientation and fit with a sine function. The bias level of the fitted sines, i.e., the gravity-independent gain change, was -29+/-10% (SD). The gains varied around this bias as a function of head position by +/-18+/-6%, which were the gravity-dependent gain changes. The gravity-dependent gain changes induced by only 1 h of adaptation persisted, gradually declining over several days. We conclude that there is a component of the vertical aVOR gain change in humans that is dependent on the head orientation in which the gain was adapted, and that this dependence can persist for substantial periods.