The temporal impulse response function in infantile nystagmus

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment 2, temporal contrast sensitivity functions were determined for a 3-cpd horizontal square-wave grating that underwent counterphase flicker at temporal frequencies between 1 and 40 Hz. Data were obtained for 2 subjects with predominantly pendular IN and 8 normal observers in Experiment 1 and for 3 subjects with IN and 4 normal observers in Experiment 2. Temporal impulse response functions (TIRFs) were estimated as the impulse response of a linear second-order system that provided the best fit to the increment threshold data in Experiment 1 and to the temporal contrast sensitivity functions in Experiment 2. Estimated TIRFs of the subjects with pendular IN have natural temporal frequencies that are significantly faster than those of normal observers (ca. 13 vs. 9 Hz), indicating an accelerated temporal response to visual stimuli. This increase in response speed is too small to account by itself for the virtual absence of perceived motion smear in subjects with IN, and additional neural mechanisms are considered.     

Asymmetrical perception of motion smear in infantile nystagmus

Normal observers perceive less motion smear if a target moves in the opposite direction of a smooth eye movement than if the target moves to produce the same retinal image speed in the same direction as the eye movement. This study investigated whether a similar asymmetrical attenuation of perceived motion smear occurs in observers with infantile nystagmus (IN). Observers (N = 3) viewed a laser spot that moved for 100 or 125 ms to the right or left at a speed between 5 and 60°/s during the slow phase of jerk IN. After each trial, the observer adjusted the length of a bright line to match the extent of the perceived smear. Across observers, the average duration of perceived smear was 39 and 106 ms, respectively, for relative motion of the laser spot in the opposite vs. the same direction as the IN slow phase. In one observer with periodic alternating nystagmus, the direction of spot motion that produced less perceived smear reversed with an alternation in the direction of the IN slow phase. The reduction of perceived motion smear for relative target motion in the opposite direction of IN slow phases is attributed to extra-retinal signals that accompany IN. As during normal eye movements, the reduction of perceived smear for this direction of relative motion should foster the perception of clarity in the stationary visual world.     

Kestenbaum procedure with posterior fixation suture for anomalous head posture in infantile nystagmus

Background  The purpose of this study was to report the effect of combining the Kestenbaum procedure with posterior fixation suture for infantile horizontal nystagmus with anomalous head posture (AHP) in children. Methods  Nine consecutive patients who underwent combined Kestenbaum procedure plus posterior fixation suture to the recessed muscles at the same time were retrospectively studied. All patients were orthotropic before surgery and were followed for at least 6 months. Pre- and postoperative AHP and binocular corrected visual acuity (BCVA), and ocular alignment were assessed. Results  Mean age at surgery was 4.8 ± 1.5 years. The average follow-up was 29.7 months. The average head turn preoperatively was 27.4° and postoperatively 7.2°. The average net change in AHP was 24.8° (P = 0.008). Seven of 9 patients (78%) achieved a residual head turn of 10° or less. The average Log Mar BCVA was 0.33 preoperatively and 0.31 postoperatively (P = 0.68). Only 1 patient needed additional surgery for residual horizontal AHP. No patient developed strabismus. Conclusion  Combined Kestenbaum procedure with posterior fixation suture was an effective and stable procedure in reducing AHP of the range of 20° to 35° in children with infantile nystagmus. Presented in part as a poster at the American Association for Pediatric Ophthalmology and Strabismus 32nd Annual Meeting in Keystone, Colorado, March 15-19, 2006. The authors have no proprietary interest related to this article. The authors have full control of all primary data and we agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review our data upon request.     

婴儿眼球震颤综合征的治疗进展

婴儿眼球震颤综合征(infantile nystagmus syndrome,INS)是一种在生后早期出现的病理性眼球震颤,以双眼非自主性共轭眼球运动为临床特征,会破坏双眼视力及视功能,同时是引起弱视、斜视以及斜颈的原因之一.目前尚无治愈INS的方法,但治疗方法有许多进展,如视光学治疗采用框架眼镜、角膜接触镜、三棱镜、低视力助视器及激光,药物治疗采用碳酸酐酶抑制剂、肉毒素眼外肌注射等,生物反馈治疗采用听觉反馈等,以及新的手术方法.     

婴儿眼球震颤综合征的研究进展

婴儿眼球震颤综合征(infantile nystagmus syndrome,INS)是一种先天性病理性眼球震颤,以双眼非自主性的共轭摆动和反向视动性眼球震颤为特征表现。INS患者可合并弱视、斜视及斜颈等,常有不同程度的视功能障碍。该病病因尚不明确,且无法完全治愈,应尽早对INS进行检查和适当干预。基于国内外对INS的研究成果,本文首先总结了INS目前所知的病因及发生机制; 其次,介绍了INS近年提出的检查方法与治疗方案,总结了相关临床实践中存在的问题,并在此基础上,对未来可能的研究方向给出了建议,旨在为临床应用及未来研究方向提供参考。     

Effects of stimulus size and luminance on oscillopsia in congenital nystagmus

Although the absence of oscillopsia is a common feature of congenital nystagmus (CN), it is occasionally noted by patients under poor viewing conditions and has been provoked in laboratory settings with stabilised images. In the present study, the effects of reductions in background stimulus size and luminance on perceptual stability in CN were examined. Sixteen CN subjects were first interviewed using a structured questionnaire about whether they ever experienced oscillopsia and, if so, under what circumstances and with what perceptions. They next fixated an LED centred in projected images of three sizes (21x14 degrees, 10x6 degrees and 7x4 degrees) and four luminance levels (115.5, 24.5, 2.7 and 0.1 cd/m2, with contrasts from 96 down to 20%). Eye movements were recorded with a limbal tracker. They were asked after viewing each image "whether anything happened to the image while they watched it." Occasional oscillopsia was reported by 12/16 of the CN subjects on the questionnaire. In the laboratory, 13/16 subjects experienced oscillopsia in some manner for at least one of the stimuli. 8/13 CN subjects experienced it for the dimmest and smallest slides. 11/13 perceived certain parts (either the LED or background) of the visual stimuli as moving, with the perception of LED movement most pronounced at low background luminance. Foveation did not differ when trials with and without reported oscillopsia were compared (independent samples t-test, p>0.05). Oscillopsia may occur in CN with normal viewing of bright fixation targets against dim backgrounds. Under these conditions, the oscillopsia may be spatially inhomogeneous. Luminance differences between the fixation point and surround may have caused transmission time differences as the image moved across the retina, therefore leading to the perception of motion in one portion of the scene and not the other.     

Topical lambda-cyhalothrin in reducing eye oscillations in a canine model of infantile nystagmus syndrome

Purpose:To determine the ocular and systemic safety of using topical Lambda-Cyhalothrin (LCL) in a canine model of infantile nystagmus syndrome (INS). The rationale for this proposal is based on a case study of a patient whose INS improved after inadvertent ocular exposure to a pyrethroid pesticide containing LCL.Methods:After in-vitro safety testing and IUCAC approval, we studied increasing concentrations of topical LCL drops (0.002% to 0.07%) in canines with a purposely bred defect in the RPE65 gene resulting in both retinal degeneration and INS. We collected data on ocular and systemic effects and performed eye-movement recordings (EMR).Results:At the 0.07% concentration dose of LCL, there was minimal, reversible, conjunctival hyperemia. There was no other ocular or systemic toxicity. At the 0.06% dose, there was a visible decrease in the INS and EMR showed a 153%–240% increase in the nystagmus acuity function and a 30%–70% decrease in amplitude across gaze. There was also a 40%–60% decrease in intraocular pressure while on the drop in both eyes.Conclusion:This animal study suggests this new pharmacological agent has potential for topical treatment of both INS and diseases with raised intraocular pressure. Further, this new treatment approach confirms the importance of extraocular muscle proprioception in ocular motor diseases and their treatment.     

Tenotomy procedure alleviates the "slow to see" phenomenon in infantile nystagmus syndrome: model prediction and patient data

Our purpose was to perform a systematic study of the post-four-muscle-tenotomy procedure changes in target acquisition time by comparing predictions from the behavioral ocular motor system (OMS) model and data from infantile nystagmus syndrome (INS) patients. We studied five INS patients who underwent only tenotomy at the enthesis and reattachment at the original insertion of each (previously unoperated) horizontal rectus muscle for their INS treatment. We measured their pre- and post-tenotomy target acquisition changes using data from infrared reflection and high-speed digital video. Three key aspects were calculated and analyzed: the saccadic latency (Ls), the time to target acquisition after the target jump (Lt) and the normalized stimulus time within the cycle. Analyses were performed in MATLAB environment (The MathWorks, Natick, MA) using OMLAB software (OMtools, available from http://www.omlab.org). Model simulations were performed in MATLAB Simulink environment. The model simulation suggested an Lt reduction due to an overall foveation-quality improvement. Consistent with that prediction, improvement in Lt, ranging from approximately 200 ms to approximately 500 ms (average approximately 280 ms), was documented in all five patients post-tenotomy. The Lt improvement was not a result of a reduced Ls. INS patients acquired step-target stimuli faster post-tenotomy. This target acquisition improvement may be due to the elevated foveation quality resulting in less inherent variation in the input to the OMS. A refined behavioral OMS model, with "fast" and "slow" motor neuron pathways and a more physiological plant, successfully predicted this improved visual behavior and again demonstrated its utility in guiding ocular motor research.     

Eye movements elevate crowding in idiopathic infantile nystagmus syndrome

Idiopathic infantile nystagmus syndrome is a disorder characterised by involuntary eye movements, which leads to decreased acuity and visual function. One such function is visual crowding – a process whereby objects that are easily recognised in isolation become impaired by nearby flankers. Crowding typically occurs in the peripheral visual field, although elevations in foveal vision have been reported in congenital nystagmus, similar to those found with amblyopia. Here, we examine whether elevated foveal crowding with nystagmus is driven by similar mechanisms to those of amblyopia – long-term neural changes associated with a sensory deficit – or by the momentary displacement of the stimulus through nystagmus eye movements. A Landolt-C orientation identification task was used to measure threshold gap sizes with and without either horizontally or vertically placed Landolt-C flankers. We assume that a sensory deficit should give equivalent crowding in these two dimensions, whereas an origin in eye movements should give stronger crowding with horizontal flankers given the predominantly horizontal eye movements of nystagmus. We observe elevations in nystagmic crowding that are above crowding in typical vision but below that of amblyopia. Consistent with an origin in eye movements, elevations were stronger with horizontal than vertical flankers in nystagmus, but not in typical or amblyopic vision. We further demonstrate the same horizontal elongation in typical vision with stimulus movement that simulates nystagmus. Consequently, we propose that the origin of nystagmic crowding lies in the eye movements, either through image smear of the target and flanker elements or through relocation of the stimulus into the peripheral retina.     

Being "slow to see" is a dynamic visual function consequence of infantile nystagmus syndrome: model predictions and patient data identify stimulus timing as its cause

The objective of this study was to investigate the dynamic properties of infantile nystagmus syndrome (INS) that affect visual function; i.e., which factors influence latency of the initial reflexive saccade (Ls) and latency to target acquisition (Lt). We used our behavioral ocular motor system (OMS) model to simulate saccadic responses (in the presence of INS) to target jumps at different times within a single INS cycle and at random times during multiple cycles. We then studied the responses of 4 INS subjects with different waveforms to test the model's predictions. Infrared reflection was used for 1 INS subject, high-speed digital video for 3. We recorded and analyzed human responses to large and small target-step stimuli. We evaluated the following factors: stimulus time within the cycle (Tc), normalized Tc (Tc%), initial orbital position (Po), saccade amplitude, initial retinal error (e(i)), and final retinal error (e(f)). The ocular motor simulations were performed in MATLAB Simulink environment and the analysis was performed in MATLAB environment using OMLAB software. Both the OMS model and OMtools software are available from http://http:www.omlab.org. Our data analysis showed that for each subject, Ls was a fixed value that is typically higher than the normal saccadic latency. Although saccadic latency appears somewhat lengthened in INS, the amount is insufficient to cause the "slow-to-see" impression. For Lt, Tc% was the most influential factor for each waveform type. The main refixation strategies employed by INS subjects made use of slow and fast phases and catch-up saccades, or combinations of them. These strategies helped the subjects to foveate effectively after target movement, sometimes at the cost of increased target acquisition time. Foveating or braking saccades intrinsic to the nystagmus waveforms seemed to disrupt the OMS' ability to accurately calculate reflexive saccades' amplitude and refoveate. Our OMS model simulations demonstrated this emergent behavior and predicted the lengthy target acquisition times found in the patient data.     

应用改进的眼震图检查先天性眼球震颤

目的评价改进后的眼震图对先天性眼球震颤波形的分析,为其手术治疗提供较为精确的量化标准.方法改进电生理仪的视网膜电图(EOG)程序,分别记录68例患者33cm原在位、右5°、10°、15°、20°,左5°、10°、15°、20°,3m原在位及闭眼的波形,并对其中28例手术患者术前和术后的眼震图进行比较.结果68例患者中,跳动型48例,其中水平跳动46例,垂直跳动2例;水平钟摆型20例.跳动型中,有代偿头位的40例,钟摆型无明显代偿头位.28例手术患者中,水平跳动型26例,水平钟摆型2例.26例跳动型患者均有中间位和代偿头位.术后20例代偿头位消失,6例代偿头位在左5°～10°.按震频、振幅、震强的分组中,处于中等震频、振幅、震强范围内的多见.结论改进的眼震图可以对眼震的振幅、震频、震强、中间位进行量化的检测,从而指导其治疗.     

Infantile nystagmus: current concepts in diagnosis and management

This review examines current approaches to the diagnosis and management of congenital forms of nystagmus. Emphasis is placed on diagnostic features that are amenable to clinical identification but those issues that can be addressed only with more detailed investigations, such as eye movement recording, are indicated. Non‐surgical management, including prism spectacles, contact lenses and vision therapy, is discussed, as are surgical approaches. Because many aspects of congenital forms of nystagmus, particularly as experienced by patients with the condition in their normal lives, are poorly addressed in both the clinical and research literature, these limitations are also highlighted.     

Long-term results of four horizontal rectus muscle recession in nystagmus treatment

Purpose: To report the long-term results of four horizontal rectus muscle recessions that were performed for infantile nystagmus syndrome treatment.

Methods: In this case series, patients with infantile nystagmus syndrome who had four horizontal muscle recessions previously were recruited and ophthalmological examination and electronystagmography recordings were performed. Objectively, amplitude and frequency of nystagmus were measured from the recordings and the intensity was calculated. Visual acuity, stereopsis, and alignment were evaluated and compared with the preoperative and postoperative values.

Results: The records of the 12 patients who had four horizontal rectus muscle recession surgery were evaluated and six patients (5 male, 1 female) who had regular follow-ups were included in this study. Mean follow-up was 14.17?±?0.41 years (minimum 14 years, maximum 15 years) and mean age of patients at the last visit was 22 years (20-28 years). On subjective evaluation, two-thirds (4/6) of the patients were satisfied with the surgical results and had the impression that after surgery, nystagmus decreased in intensity and head posture improved. On objective evaluation, visual acuity was found to be the same, however, stereopsis improved (preoperatively and postoperatively median stereopsis was 600?sec arc vs 200?sec arc final). The decrease in nystagmus amplitude and frequency was still maintained.

Conclusions: Nystagmus surgery on four horizontal rectus muscles has positive effects on binocular function and nystagmus parameters in the long-term follow-up. As we could not treat the primary pathology, the visual acuity was about the same but the decrease in nystagmus amplitude and frequency was still maintained with better stereopsis, and patient satisfaction.     

Surgery for the treatment of vertical head posturing associated with infantile nystagmus syndrome: results in 24 patients

Background: The study of the clinical and electrophysiological effects of eye muscle surgery on patients with infantile nystagmus has broadened our knowledge of the disease and its interventions. Design: Prospective, comparative, interventional case series. Participants: Twenty‐four patients with a vertical head posture because of electrophysiologically diagnosed infantile nystagmus syndrome. The ages ranged from 2.5 to 38 years and follow up averaged 14.0 months. Methods: Thirteen patients with a chin‐down posture had a bilateral superior rectus recession, inferior oblique myectomy and a horizontal rectus recession or tenotomy. Those 11 with a chin‐up posture had a bilateral superior oblique tenectomy, inferior rectus recession and a horizontal rectus recession or tenotomy. Main Outcome Measures: Outcome measures included: demography, eye/systemic conditions and preoperative and postoperative; binocular, best optically corrected, null zone acuity, head posture, null zone foveation time and nystagmus waveform changes. Results: Associated conditions were strabismus in 66%, ametropia in 96%, amblyopia in 46% and optic nerve, foveal dysplasia or albinism in 54%. Null zone acuity increased at least 0.1 logMAR in 20 patients (P < 0.05 group mean change). Patients had significant (P < 0.05) improvements in degrees of head posture, average foveation time in milliseconds and infantile nystagmus syndrome waveform improvements. Conclusions: This study illustrates a successful surgical approach to treatment and provides expectations of ocular motor and visual results after vertical head posture surgery because of an eccentric gaze null in patients with infantile nystagmus syndrome.     

Postnatal development of optokinetic after nystagmus in human infants

During the first few months of life after birth human infants when tested monocularly move their unoccluded eye nasalward in darkness after viewing a large textured visual field moving either nasalward or temporalward. The eye movements in darkness are optokinetic after nystagmus (OKAN) which is an aftereffect of a reflex horizontal following eye movement, optokinetic nystagmus (OKN). Not until 4-5 months of age did temporalward field motion evoke OKAN with temporalward slow phase. The nasalward slow phase of OKAN that responded earlier to temporalward field motion appears to underlie the delayed development of reflex following eye movements in the temporalward direction.     

眼球震颤的诊断与治疗研究进展

眼球震颤是常见的眼球运动障碍疾病,临床诊治困难。随着近年眼球运动记录方法的进步和药物、手术及基因治疗的研究进展,为临床该病的诊断和治疗提供了更多的选择,也为眼球震颤患者带来新的希望。本文就该病诊断与治疗的最新研究进展进行了综述。     

Foveation dynamics in congenital nystagmus III: Vestibulo-ocular reflex

It has been shown that, during fixation of a stationary target with a fixed head, an individual with congenital nystagmus (CN) can repeatedly (beat-to-beat) foveate (within 13 minarc) and maintain low retinal slip velocities (less than 4°/sec). With the head in motion, vestibuloocular reflex (VOR) data showed eye velocities during these foveation periods that approximation head veloicty. Despite some claims that the VOR of CN subjects was deficient or absent, individuals with CN hardly ever complain of oscillopsia or exhibit any of the symptoms that would accompany such deficits in the VOR, whether during simple walking and running or while skiing down a mogul field. We developed and describe several different and unrelated methods to accurately assess the function of the VOR in an individual with typical idiopathic CN. We investigated the dynamics of CN foveation periods during head rotation to test the hypothesis that eye velocities would match head velocities during these periods. At about 1 Hz, horizontal VOR instantaneous (beat-to-beat) gains were 0.96 in the light and 0.94 in the dark while imagining a stationary target. Vertical VOR gains were 1.00 and 0.99 for these two conditions at the same frequency; the CN was horizontal. Also, during the VOR there is a CN neutral-zone shift comparable to that found during smooth pursuit. Our methods demonstrated that gaze velocity was held constant during foveation periods and we conclude that the VOR in this subject is functioning normally in the presence of the CN oscillation. Based on our findings in this and previous studies, we hypothesize that CN may be due to a peripheral instability.General Terms BS Braking saccade - CN Congenital nystagmus - CS Catch-up saccade - DNZ Dynamic neutral zone - FS Foveating saccade - NFP Non-foveating peak - SNZ Static neutral zone - SD Standard deviation - VOR Vestibulo-ocular reflex CN Waveforms JLef Jerk left with extended foveation - Pfr(l)s Pendular with right (left) foveating saccades - PPr(l)fs Pseudopendular with right (left) foveating saccades - R(L)PC Right (left) pseudocycloid Calculated (Statistical) Terms Gav Average gain - Gfp Gain calculated during the foveation period - RERfp Mean retinal error position during foveation period     

Time-varying, slow-phase component interaction in congenital nystagmus

We investigated the nystagmus of a 12-year-old boy with suspected X-linked congenital nystagmus (CN) and exophoria to determine the underlying mechanisms and component signals in the 'dual-velocity' and other slow phases of his Asymmetric (a)Periodic Alternating Nystagmus (APAN). Fast Fourier transforms (FFT) were performed on the waveforms and residual data after subtracting a sawtooth waveform whose amplitude and frequency matched those of the jerk nystagmus. The FFT analyses identified two frequency components (jerk--4 Hz and pendular--4 and 8 Hz, variable) that varied differently in intensity and frequency/phase over the time-course of the APAN. We synthesized each of the patient's slow phases using summation of sawtooth and sinusoidal waveforms. The resulting waveforms included jerk (with different slow-phase appearances), dual jerk, and pendular. We demonstrated that the pendular nystagmus seen during the neutral phase of APAN and the appearance of either decelerating (mimicking latent nystagmus), dual-velocity, or dual-jerk slow phases can be explained and produced by the summation of linear and pendular components of variable amplitudes and frequencies/phases. Thus, one mechanism may be responsible for all the variation seen in this patient's slow phases, rather than the less parsimonious hypothesis of a switched-tonic-imbalance mechanism that we had originally suggested to simulate the dual-velocity waveform.     

Foveation dynamics in congenital nystagmus II: Smooth pursuit

It has been shown that, during 5 seconds of fixation, an individual with congenital nystagmus (CN) can repeatedly (beat-to-beat) foveate (SD = 12.87 minarc) and maintain low retinal slip velocities (SD = 118.36 minarc/sec). Smooth pursuit data from several CN subjects showed that eye velocities during these foveation intervals approximated target velocity. Despite some claims that CN is caused by absent or reversed smooth pursuit, those with CN hardly ever experience oscillopsia or exhibit any accompanying symptoms of such deficits in pursuit; they are able to master sports requiring tracking of rapidly moving small objects (e.g. racquetball or handball). We developed and describe several new methods to accurately assess the function of smooth pursuit in an individual with typical idiopathic CN. We investigated the dynamics of CN foveation periods during smooth pursuit to test the hypothesis that eye velocities would match target velocities during these periods. Unity or near-unity instantaneous (beat-to-beat) pursuit gains of both experimenter-moved and subject-moved targets at peak velocities ranging from only a few deg/sec up to 210°/sec were measured. The dynamic neutral zone was found to shift oppositely to target direction by amounts proportional to the increase in target speed. Our methods proved that eye velocity is made to match target velocity during the foveation intervals and support the conclusion that smooth pursuit in individuals with CN is functioning normally in the presence of the CN oscillation. In addition, we hypothesize that the same fixation mechanism that prevents oscillopsia during fixation of stationary targets, also does so during pursuit.General Terms CN Congenital nystagmus - CS Catch-up saccade - DNZ Dynamic neutral zone - SNZ Static neutral zone - SD Standard deviation CN Waveforms Jef Jerk with extended foveation - JR(L) Jerk right (left) - JR(L)ef Jerk right (left) with extended foveation - Pfs Pendular with foveating saccades - Pfl(r)s Pendular with left (right) foveating saccades - PPrfs Pseudopendular with right foveating saccades - R(L)PC Right (left) pseudocycloid Calculated (Statistical) Terms Gav Average gain - Gfp Gain calculated during the foveation period - RERfp Mean retinal error position during foveation period