Z. I. Wang

Infantile nystagmus syndrome: Broadening the high-foveation-quality field with contact lenses.

We investigated the effects of contact lenses in broadening and improving the high-foveation-quality field in a subject with infantile nystagmus syndrome (INS). A high-speed, digitized video system was used for the eye-movement recording. The subject was asked to fixate a far target at different horizontal gaze angles with contact lenses inserted. Data from the subject while fixating at far without refractive correction and at near (at a convergence angle of 60 PD), were used for comparison. The eXpanded Nystagmus Acuity Function (NAFX) was used to evaluate the foveation quality at each gaze angle. Contact lenses broadened the high-foveation-quality range of gaze angles in this subject. The broadening was comparable to that achieved during 60 PD of convergence although the NAFX values were lower. Contact lenses allowed the subject to see “more” (he had a wider range of high-foveation-quality gaze angles) and “better” (he had improved foveation at each gaze angle). Instead of being contraindicated by INS, contact lenses emerge as a potentially important therapeutic option. Contact lenses employ afferent feedback via the ophthalmic division of the V cranial nerve to damp INS slow phases over a broadened range of gaze angles. This supports the proprioceptive hypothesis of INS improvement.

Extraocular proprioception and new treatments for infantile nystagmus syndrome

Our goal is to develop the proprioceptive hypothesis for nystagmus damping; and present the resulting therapies for the treatment of infantile nystagmus syndrome (INS) and acquired nystagmus. Contact lenses, cutaneous stimulation, and neck-muscle vibration damped INS. Four-muscle tenotomy and reattachment was hypothesized as a treatment for INS in 1979 and successfully demonstrated to improve foveation in a canine model of INS and seesaw nystagmus in 1998 and in humans with INS (masked-data, NEI Clinical Trial) in 2003. Subsequently, tenotomy successfully damped acquired pendular nystagmus and oscillopsia in two MS patients and downbeat nystagmus in another. Tenotomy, used in isolation or combination with existing nystagmus and strabismus surgeries, damps different types of nystagmus in their plane of action. Recent neuroanatomical and neurophysiological discoveries support the hypothesis that proprioception is the mechanism for INS damping and allow more realistic models of peripheral ocular motor pathways.

Using the NAFX to Measure the Effectiveness over Time of Gene Therapy in Canine LCA

PURPOSE To use ocular motility recordings to determine the changes over time of infantile nystagmus syndrome (INS) in RPE65-deficient canines with Leber Congenital Amaurosis (LCA) and assess the time course of the recalibration of the ocular motor system (OMS). METHODS Nine dogs were treated bilaterally with AAV-RPE65. A second cohort of four dogs was treated with AAV2.RPE65, an optimized vector. Their fixation eye movements were recorded before treatment and at 4-week intervals for 3 months, by using high-speed (500 Hz) digital videography. The dogs were suspended in a sling and encouraged to fixate on distant (57 inches) targets at gaze angles varying between +/-15 degrees horizontally and +/-10 degrees vertically. The records for each eye were examined for qualitative changes in waveform and for quantitative changes in centralisation with the expanded nystagmus acuity function (NAFX) and compared with ERG results for restoration of receptor function. RESULTS First group: Before treatment, five of the dogs had clinically apparent INS with jerk, pendular, or both waveforms and with peak-to-peak amplitudes as great as 15 degrees . One dog had intermittent nystagmus. At the 1- and 2-month examinations, no change in nystagmus waveform or NAFX was observed in any of the initial dogs, while at 10 weeks, one dog treated bilaterally with the standard dosage showed reduced nystagmus in only one eye. The other eye did not respond to treatment, as confirmed by ERG. This result was unexpected since it was previously documented that unilateral treatment leads to bilateral reduction of INS. The other dog treated with the standard dosage showed no reduction of its small-amplitude, high-frequency pendular nystagmus despite positive ERG responses. Second group: Only one dog of the four had clinically detectable INS, similar in characteristics to that seen in the affected dogs of the first group. Unlike any previous dog studied, this one showed a damping of the nystagmus within the first 4 weeks after treatment. CONCLUSIONS In all but one of the cases in which OMS recalibration occurred, as measured by the clinical appearance of nystagmus and by quantitative measurement using the NAFX, the improvement was apparent no sooner than 10 weeks after treatment. Longer term, dose-related studies are needed to determine the minimum necessary degree of restored receptor functionality, the duration after rescue for recalibration of the OMS, and the conditions under which recalibration information can successfully affect the contralateral eye.

A Review of the Tenotomy Nystagmus Surgery: Origin, Mechanism, and General Efficacy

Tenotomy nystagmus surgery neither “weakens” nor “strengthens” the extraocular muscles; it is not strabismus surgery. Tenotomy effectively decreases the gain of the ocular motor plant to small, non-saccadic signals and was hypothesized to be efficacious for other types of nystagmus in addition to infantile nystagmus; it has subsequently been shown to damp various types of acquired nystagmus (pendular and jerk, horizontal and vertical) and reduce their associated oscillopsia. The eXpanded Nystagmus Acuity Function now allows visual acuity improvements to be estimated prior to surgery—something never before possible. More research into proprioceptive tension control should provide non-surgical methods to achieve the therapeutic improvements of tenotomy.

Eye-movement-based assessment of visual function in patients with infantile nystagmus syndrome.

Purpose. Infantile Nystagmus Syndrome (INS) is an ocular motor system dysfunction characterized by the rhythmic to-and-fro oscillations of the eyes. Traditionally, the assessment of INS visual function solely focused on null- or primary-position visual acuity. Our purpose is to use the past four decades of INS research to introduce a more complete assessment of visual function in patients with INS. Methods. All eye-movement data were obtained using high-speed digital video, infrared reflection, or scleral search coil systems. Results. We have introduced four important aspects of a more complete INS visual function assessment: the eXpanded Nystagmus Acuity Function and visual acuity measurements in primary position; broadness of the eXpanded Nystagmus Acuity Function peak and high-acuity field; target acquisition time; and gaze-maintenance capability. Conclusions. Visual function in patients with INS is multifactorial and the simple assessment of primary position visual acuity is both inadequate and may not be the most important characteristic in overall visual function. A more complete visual function assessment should also include primary and lateral gaze eye-movement and visual acuity examinations, target acquisition time and gaze holding.

A reinterpretation of the purpose of the translational vestibulo-ocular reflex in human subjects.

In a prior study we reported that the human translational vestibulo-ocular reflex (tVOR) in response to vertical (bob) 2 Hz oscillations generated eye rotations of only 60% of those required to keep the eyes pointed at a stationary visual target, whether located at near (approximately 17 cm) or far (2 m). Best responses occurred in ambient illumination and we concluded that relative image motion between the target and background was an important determinant of tVOR behaviour. To investigate further how visual conditions influenced tVOR, we measured responses as subjects binocularly viewed the bridge of their own nose in a mirror at approximately 8.5 cm, a visual condition that required similar convergence to viewing the near target, but cancellation of tVOR. Median tVOR cancellation gain [(near-viewing response-mirror viewing response)/near-viewing response] was 0.81 (range 0.55-0.97), which was substantially greater than the gain of smooth visual tracking of a large visual display moving at 2 Hz (median gain 0.27, range 0.09-0.42). Thus, visual inputs other than smooth tracking must contribute to tVOR cancellation. We then compared tVOR response to 2 Hz bob as subjects fixed upon a visual target at 17 cm and viewed a large textured background at 1.5 m that was either stationary or moving at 2.1 Hz. Vertical eye rotations waxed and waned as a function of the difference between platform and background oscillations. These findings support our hypothesis that tVOR evolved not to stabilize the image of the target on the fovea, but rather to minimize retinal image motion between objects lying in different planes, in order to optimize motion parallax information. A geometrically based optimization function is proposed to account for tVOR responses at different target distances.

Wavelet Analysis in Infantile Nystagmus Syndrome: Limitations and Abilities

PURPOSE To investigate the proper usage of wavelet analysis in infantile nystagmus syndrome (INS) and determine its limitations and abilities. METHODS Data were analyzed from accurate eye-movement recordings of INS patients. Wavelet analysis was performed to examine the foveation characteristics, morphologic characteristics and time variation in different INS waveforms. Also compared were the wavelet analysis and the expanded nystagmus acuity function (NAFX) analysis on sections of pre- and post-tenotomy data. RESULTS Wavelet spectra showed some sensitivity to different features of INS waveforms and reflected their variations across time. However, wavelet analysis was not effective in detecting foveation periods, especially in a complicated INS waveform. NAFX, on the other hand, was a much more direct way of evaluating waveform changes after nystagmus treatments. CONCLUSIONS Wavelet analysis is a tool that performs, with difficulty, some things that can be done faster and better by directly operating on the nystagmus waveform itself. It appears, however, to be insensitive to the subtle but visually important improvements brought about by INS therapies. Wavelet analysis may have a role in developing automated waveform classifiers where its time-dependent characterization of the waveform can be used. The limitations of wavelet analysis outweighed its abilities in INS waveform-characteristic examination.