Visual functioning in adults with Idiopathic Infantile Nystagmus Syndrome (IINS).

PURPOSE: IINS is associated with mild/moderate visual impairment, strabismus and compensatory head postures (CHP), which can negatively impact quality of life. Standard visual acuity assessments tend to underestimate the effect of IINS on visual functioning. Published evidence on the effect of INS on quality of life is slowly emerging. Our study examines visual functioning of adults with IINS using the National Eye Institute Visual Function Questionairre-25 (VFQ-25). METHODS: 38 participants were recruited to participate in the study. All participants underwent detailed clinical examination, as well as appropriate investigations and were asked to complete the self administered VFQ-25. RESULTS: 35/38 participants completed the questionnaire. The mean age of the population was 35.1 years (range 17-64). Mean overall VFQ-25 score at baseline was 65 (SD 13, range 34-91). Participants specifically demonstrated lowest scores for the impact of IINS on mental health, role limitations and dependency. 26/35 of participants were not driving, either due to sub-normal vision, lack of confidence or difficulties with contrast sensitivity. CONCLUSIONS: IINS can have a greater than expected impact on an individual's quality of life, without necessarily causing markedly reduced visual acuity. Our study showed lowest scores in the domains of mental health and wellbeing. Patients also reported reduced visual functioning in driving, which can impact adversely on employability and independence. Visual functioning questionnaires such as the VFQ-25 may provide more functional information on the impact of nystagmus on an individual's quality of life than objective measures such as high contrast Snellen and/or LogMAR visual acuity.

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 125ms to the right or left at a speed between 5 and 60 degrees /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 106ms, 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.

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.

Task-induced stress and motivation decrease foveation-period durations in infantile nystagmus syndrome.

PURPOSE: To investigate the effect of visual demand, task-related physiological stress, and motivation on the nystagmus waveform of 19 subjects with infantile nystagmus syndrome (INS). METHODS: Subjects viewed a Landolt C of varying orientation and size, and indicated its orientation via arrow keys on a keyboard. Mental arithmetic was performed in conjunction with the visual task. Subjects then underwent a reward-penalty paradigm. Eye movements and heart rates were recorded during all experiments. RESULTS: Task-related physiological stress and motivation were reflected in an increase in heart rate and led to an increase in the amplitude, frequency, and intensity of the nystagmus waveform and a decrease in foveation-period durations. Changes in heart rate did not correlate with changes in waveform parameters for all experiments. CONCLUSIONS: The results show, for the first time, the negative impact of task-induced stress and/or motivation on the characteristics of INS. This finding has important implications for individuals with INS, because stress may arise in everyday situations, such as driving or when undertaking an examination.

Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7.

Idiopathic infantile nystagmus (IIN) consists of involuntary oscillations of the eyes. The familial form is most commonly X-linked. We recently found mutations in a novel gene FRMD7 (Xq26.2), which provided an opportunity to investigate a genetically defined and homogeneous group of patients with nystagmus. We compared clinical features and eye movement recordings of 90 subjects with mutation in the gene (FRMD7 group) to 48 subjects without mutations but with clinical IIN (non-FRMD7 group). Fifty-eight female obligate carriers of the mutation were also investigated. The median visual acuity (VA) was 0.2 logMAR (Snellen equivalent 6/9) in both groups and most patients had good stereopsis. The prevalence of strabismus was also similar (FRMD7: 7.8%, non-FRMD7: 10%). The presence of anomalous head posture (AHP) was significantly higher in the non-FRMD7 group (P < 0.0001). The amplitude of nystagmus was more strongly dependent on the direction of gaze in the FRMD7 group being lower at primary position (P < 0.0001), compared to non-FRMD7 group (P = 0.83). Pendular nystagmus waveforms were also more frequent in the FRMD7 group (P = 0.003). Fifty-three percent of the obligate female carriers of an FRMD7 mutation were clinically affected. The VA's in affected females were slightly better compared to affected males (P = 0.014). Subnormal optokinetic responses were found in a subgroup of obligate unaffected carriers, which may be interpreted as a sub-clinical manifestation. FRMD7 is a major cause of X-linked IIN. Most clinical and eye movement characteristics were similar in the FRMD7 group and non-FRMD7 group with most patients having good VA and stereopsis and low incidence of strabismus. Fewer patients in the FRMD7 group had AHPs, their amplitude of nystagmus being lower in primary position. Our findings are helpful in the clinical identification of IIN and genetic counselling of nystagmus patients.

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.

Biologically relevant models of infantile nystagmus syndrome: the requirement for behavioral ocular motor system models.

Infantile nystagmus syndrome (INS) is a combination of several types of nystagmus, each representing dysfunction in one subsystem of the ocular motor system (OMS) and having characteristic waveforms. Eye-movement recordings are the only certain way to identify IN and differentiate it from other types. The waveform classification scheme in use for 30 years is both accurate, inclusive, and suggests the underlying subsystem instabilities. In different individuals, they may appear at birth (hard wired) or in early infancy (developmental). The primary subsystem instability in IN is hypothesized to lie in the normally underdamped smooth pursuit system; vestibular dysfunction (imbalance) may also be present. Less often, the nucleus of the optic tract may be involved. Ocular motility studies over the past 40 years have demonstrated that saccades and gaze holding are normal in the INS and saccades contained within IN waveforms are always corrective; i.e., they cannot be the initiating movement responsible for IN. Because there are an infinite number of solutions to simulating specific waveforms, models that merely generate waveforms that resemble IN in isolation are of little use, either clinically or to increase our understanding of the underlying mechanisms of IN. A biologically relevant model of the INS should be part of, and operate within, a complete OMS model, capable of reproducing the normal ocular motor behavior of these individuals while still oscillating; i.e., the model, like the patient, must not have oscillopsia and be able to respond correctly to various target inputs.

The effects of increased visual task demand on foveation in congenital nystagmus.

Commonly, when an individual with congenital nystagmus (CN) performs a visually demanding task their nystagmus intensifies and their visual acuity decreases, probably due to poorer foveation. However, the relationship between fixation attempt and nystagmus waveform has never been quantified. In this study 14 CN subjects viewed a Landolt C of varying orientation and size. They indicated its orientation via a button array whilst eye movements were recorded. Foveation was uncorrelated with optotype size. These results suggest that CN is not exacerbated by visual demand per se rather the need to do something visually demanding of importance to the individual.

Orientation discrimination and variability of torsional eye position in congenital nystagmus.

Thresholds for discriminating the orientation of unreferenced horizontal and vertical lines were measured in subjects with congenital nystagmus (CN) and normal observers and compared to the variability of torsional eye position. Orientation thresholds were determined for horizontal and vertical lines between 0.7 degrees and 5.6 degrees in length, that were presented binocularly for 20-1280 ms. The variability of torsional eye position was assessed using the magnetic search coil technique. Orientation thresholds improved with line length and stimulus duration in both groups of observers. Some of the subjects with CN exhibited poorer than normal thresholds, particularly when the length of the line was short. In addition, orientation discrimination in the subjects with CN was consistently anisotropic, with significantly lower thresholds for horizontal than vertical lines. The standard deviations of torsional eye position were larger in the subjects with CN than in normal observers. However, orientation thresholds were poorer than expected from the variability of torsional eye position in normal observers, and better than expected on the basis of torsional variability in some of the subjects with CN. These results imply that torsional variability does not limit normal orientation thresholds and that torsional eye movements in CN are compensated partially by extraretinal signals.