Sensorineural correlates of failed functional recovery after natural regeneration of vestibular hair cells in adult mice.

Vestibular hair cells (HCs) are mechanoreceptors that sense head motions by modulating the firing rate of vestibular ganglion neurons (VGNs), whose central processes project to vestibular nucleus neurons (VNNs) and cerebellar neurons. We explored vestibular function after HC destruction in adult Pou4f3+/DTR (DTR) mice, in which injections of high-dose (50 ng/g) diphtheria toxin (DT) destroyed most vestibular HCs within 2 weeks. At that time, DTR mice had lost the horizontal vestibulo-ocular reflex (aVORH), and their VNNs failed to upregulate nuclear cFos expression in response to a vestibular stimulus (centrifugation). Five months later, 21 and 14% of HCs were regenerated in utricles and horizontal ampullae, respectively. The vast majority of HCs present were type II. This degree of HC regeneration did not restore the aVORH or centrifugation-evoked cFos expression in VNNs. The failure to regain vestibular pathway function was not due to degeneration of VGNs or VNNs because normal neuron numbers were maintained after HC destruction. Furthermore, sinusoidal galvanic stimulation at the mastoid process evoked cFos protein expression in VNNs, indicating that VGNs were able to regulate VNN activity after HC loss. aVORH and cFos responses in VNNs were robust after low-dose (25 ng/g) DT, which compared to high-dose DT resulted in a similar degree of type II HC death and regeneration but spared more type I HCs in both organs. These findings demonstrate that having more type I HCs is correlated with stronger responses to vestibular stimulation and suggest that regenerating type I HCs may improve vestibular function after HC loss.

Cognition and saccadic eye movement performance are impaired in chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) can experience cognitive dysfunction. The literature on this topic mostly reflects patient-reported measurements. Our goal was to assess cognitive function in patients with CRS using objective measures, including saccadic eye movements-a behavioral response reflecting cognitive and sensory information integration that is often compromised in conditions with impaired cognition. METHODS: Participants (N = 24 with CRS, N = 23 non-CRS healthy controls) enrolled from rhinology clinic underwent sinonasal evaluation, quality of life assessment (Sino-nasal Outcome Test 22 [SNOT-22]), and cognitive assessment with the Neuro-QOL Cognitive Function-Short Form, the Montreal Cognitive Assessment (MoCA), and recording of eye movements using video-oculography. RESULTS: Participants with CRS were more likely to report cognitive dysfunction (Neuro-QOL; 45.8% vs. 8.7%; p = 0.005) and demonstrate mild or greater cognitive impairment (MoCA; 41.7% vs. 8.7%; p = 0.005) than controls. Additionally, participants with CRS performed worse on the MoCA overall and within the executive functioning and memory domains (all p < 0.05) and on the anti-saccade (p = 0.014) and delay saccade (p = 0.044) eye movement tasks. Poorer performance on the MoCA (r = -0.422; p = 0.003) and the anti-saccade (r = -0.347; p = 0.017) and delay saccade (r = -0.419; p = 0.004) eye movement tasks correlated with worse CRS severity according to SNOT-22 scores. CONCLUSION: This study is the first to utilize objective eye movement assessments in addition to researcher-administered cognitive testing in patients with CRS. These patients demonstrated a high prevalence of cognitive dysfunction, most notably within executive functioning and memory domains, with the degree of dysfunction correlating with the severity of CRS.

Compensatory saccade in the vestibular impaired monkey.

Introduction: Loss of the vestibulo-ocular reflex (VOR) affects visual acuity during head movements. Patients with unilateral and bilateral vestibular deficits often use saccadic eye movements to compensate for an inadequate VOR. Two types of compensatory saccades have been distinguished, covert saccades and overt saccades. Covert saccades occur during head rotation, whereas overt saccades occur after the head has stopped moving. The generation of covert saccades is part of a central vestibular compensation process that improves visual acuity and suppresses oscillopsia. Understanding the covert saccade mechanism may facilitate vestibular rehabilitation strategies that can improve the patient's quality of life. To understand the brain mechanisms underlying covert saccades at the neural level, studies in an animal model are necessary. In this study, we employed non-human primates whose vestibular end organs are injured. Methods: We examined eye movement during the head-impulse test, which is a clinical test to evaluate the vestibulo-ocular reflex. During this test, the monkeys are required to fixate on a target and the head is rapidly and unexpectedly rotated to stimulate the horizontal semi-circular canals. Results: Similar to human subjects, monkeys made compensatory saccades. We compared these saccades with catch-up saccades following a moving target that simulates the visual conditions during the head impulse test. The shortest latency of the catch-up saccades was 250 ms, which indicates that it requires at least 250 ms to induce saccades by a visual signal. The latency of some compensatory saccades is shorter than 250 ms during the head impulse test, suggesting that such short latency compensatory saccades were not induced visually. The peak velocity of the short latency saccades was significantly lower than that of longer latency saccades. The peak velocity of these longer latency saccades was closer to that of visually guided saccades induced by a stepping target. Conclusion: These results are consistent with studies in human patients. Thus, this study demonstrates, for the first time, compensatory covert saccades in vestibular impaired monkeys.

The Next Challenges of Vestibular Implantation in Humans.

Patients with bilateral vestibulopathy suffer from a variety of complaints, leading to a high individual and social burden. Available treatments aim to alleviate the impact of this loss and improve compensatory strategies. Early experiments with electrical stimulation of the vestibular nerve in combination with knowledge gained by cochlear implant research, have inspired the development of a vestibular neuroprosthesis that can provide the missing vestibular input. The feasibility of this concept was first demonstrated in animals and later in humans. Currently, several research groups around the world are investigating prototype vestibular implants, in the form of vestibular implants as well as combined cochlear and vestibular implants. The aim of this review is to convey the presentations and discussions from the identically named symposium that was held during the 2021 MidWinter Meeting of the Association for Research in Otolaryngology, with researchers involved in the development of vestibular implants targeting the ampullary nerves. Substantial advancements in the development have been made. Yet, research and development processes face several challenges to improve this neuroprosthesis. These include, but are not limited to, optimization of the electrical stimulation profile, refining the surgical implantation procedure, preserving residual labyrinthine functions including hearing, as well as gaining regulatory approval and establishing a clinical care infrastructure similar to what exists for cochlear implants. It is believed by the authors that overcoming these challenges will accelerate the development and increase the impact of a clinically applicable vestibular implant.

Factors Associated with Ocular Injury in Orbital Fracture Patients: Who Requires Urgent Ophthalmic Evaluation?

Importance: Create validated criteria to identify orbital fracture patients at higher risk for significant ocular injuries. Objective: Determine history and physical examination findings in orbital fracture patients who are associated with ocular injury and warrant urgent assessment by an ophthalmologist. Design, Setting, and Participants: Retrospective chart review of 535 adult orbital fracture patients evaluated at a Level I emergency department between 2014 and 2017, without prior history of orbital fracture, ocular injury, or ocular/orbital surgery. Main Outcomes and Measure: Presence of ocular injury. Results: In total, 195 (36%) patients had an ocular injury. Those with and without ocular injury were compared in a multivariate logistic regression model including demographics, fracture characteristics, injury mechanism, and physical examination findings. Visual acuity change, radiographic retrobulbar hemorrhage, abnormal pupillary reaction, and inability to open the injured eye all had significant associations with ocular injury when other findings were controlled. Conclusion: This study shows a significant association between ocular injury and visual acuity change, retrobulbar hemorrhage, abnormal pupillary reaction, and inability to open the injured eye. These factors can help triage when to obtain an urgent ophthalmology consult.

Cerebral Visual Impairment Characterized by Abnormal Visual Orienting Behavior With Preserved Visual Cortical Activation.

Purpose: Children with cerebral visual impairment (CVI) often have abnormal visual orienting behaviors due to impaired or damaged visual cortex. Alternatively, visual-cortical function is intact but visual information is not transformed downstream into an appropriate oculomotor output (visuomotor dysfunction). We examined visual, anatomic, and oculomotor assessments to distinguish visuomotor dysfunction from CVI associated with severely reduced visual-cortical response. Methods: We reviewed the medical records from children with CVI having abnormal visual orienting behaviors, normal ocular examinations, and born near term. Relevant data were visual evoked potentials (VEPs), Teller card acuity, eye movements recorded by video-oculography (VOG), and neuroimaging (magnetic resonance imaging [MRI]) including diffusion tensor imaging (DTI) tractography. Results: Thirty subjects had visuomotor dysfunction based on a normal VEP; of these 33% had a normal MRI and 67% had white matter abnormalities associated with metabolic disease and/or decreased volume of brain parenchyma. VOG recordings showed smooth pursuit gains were uniformly reduced and saccades were dysmetric but followed the main sequence. Ten subjects had severe CVI based on VEPs at noise levels; visual acuities and MRI findings overlapped those of the visuomotor dysfunction group. Developmental delay, seizures, microcephaly, and hypotonia were common across all groups. All subjects with an abnormal conventional MRI had abnormal metrics on DTI tractography from the occipital lobe. Conclusions: A subset of patients with CVI have abnormal visual orienting behaviors despite a normal VEP (visuomotor dysfunction). A majority have abnormal white matter metrics on tractography suggesting a downstream defect in sensorimotor transformation. Clinically, visuomotor dysfunction is indistinguishable from severe CVI.

A reduced visual pathway response in infantile nystagmus syndrome.

PURPOSE: To investigate visual cortical responses in children with infantile nystagmus syndrome (INS) and the potential contribution of foveation periods. METHODS: The medical records of children with INS who had visual evoked potential (VEP) recordings to reversing checkerboards and onset of horizontal gratings were reviewed retrospectively. VEP recordings underwent objective selective averaging for extraction of brief periods having consistent amplitude and timing with the stimulus presentation. VEP amplitude, latency, and signal-to-noise ratios (SNR) were compared to results from published age-matched controls under the same conditions. Relative foveation in INS subjects was determined from the proportion of time a video-oculography recording met eye position and velocity criteria. RESULTS: A total of 26 children met inclusion criteria. Selective averaging increased VEP amplitude and SNR in INS by 270%-420% compared to standard averaging (P < 0.0001). The INS change in VEP response was greater for reversing checkerboard stimulation than horizontal-grating onset and was significantly greater than that in controls (P < 0.001). Latency was not changed by selective averaging. Relative foveation was correlated with increasing VEP amplitude (P = 0.02) and number of trials chosen for selective averaging (P < 0.01). After selective averaging, relative foveation correlated with VEP amplitude to reversing checkerboards only (P = 0.007). CONCLUSIONS: Nystagmus likely causes a reduced visual cortical response in children with INS. A significantly larger response can be extracted from brief periods during nystagmus eye movements, supporting the hypothesis that the INS visual system generates a larger cortical signal during brief foveation periods.

Two Missense CACNA1A Variants in a Single Family with Variable Neurobehavioral, Cerebellar, Epileptic, and Oculomotor Features.

We describe two novel missense variants in CACNA1A segregating in a family with variable severity of ataxia/oculomotor dysfunction, neurobehavioral impairments, and epilepsy. The most severe outcome occurred in a compound heterozygous proband, which could represent variable expression of the paternal allele or biallelic modulation of calcium channel function. Acetazolamide and lamotrigine were effective for seizure control.

Matching Misaligned Spectralis OCTs to a Reference Scan in Pediatric Glaucoma with Poor Fixation and Nystagmus.

Purpose: Poor fixation or nystagmus in children causes misalignment errors when measuring circumpapillary retinal nerve fiber layer (cpRNFL) thickness by simultaneous scanning laser ophthalmoscope imaging/optical coherence tomography (SLO/OCT). We investigated a method to assess cpRNFL from misaligned SLO/OCT scans. Methods: Heidelberg Spectralis SLO/OCT scans from a single clinical examination were retrospectively analyzed when automated eye tracking was unreliable. Retinal layer thickness was measured at overlapping match locations between a reference and misaligned scans based on the position data from simultaneously acquired SLO images. Three layers were segmented: cpRNFL, internal limiting membrane to outer nuclear layer (ILM-ONL), and total retinal thickness (TR). Accuracy was defined as the difference in thickness between the reference and misaligned scans at their match locations after correction for scan angle. Results: Thirty-five subjects, evaluated for glaucomatous nerve loss, met inclusion criteria. Group-averaged accuracy was -2.7, 1.4, and 0.3 µm for cpRNFL, ILM-ONL, and TR thickness, respectively. Across all layers, interobserver intraclass correlation coefficients ranged from 0.97 to 0.63 and the maximum Bland-Altman 95% limits of agreement were -21.6 to 20.7 µm. Variability was greatest for cpRNFL thickness and least for TR thickness. Increased variability was associated with lower signal-to-noise ratio but not with image-motion indices of shear, rotation, and scale. Conclusions: Retinal layer thickness can be compared to a reference cpRNFL OCT scan when poor fixation and nystagmus causes misalignment errors. The analysis can be performed post hoc using multiple misaligned scans from standard SLO/OCT protocols. Translational Relevance: Our method allows for assessment of cpRNFL in children who fail eye tracking.

The vestibular implant: Opinion statement on implantation criteria for research.

This opinion statement proposes a set of candidacy criteria for vestibular implantation of adult patients with bilateral vestibulopathy (BVP) in a research setting. The criteria include disabling chronic symptoms like postural imbalance, unsteadiness of gait and/or head movement-induced oscillopsia, combined with objective signs of reduced or absent vestibular function in both ears. These signs include abnormal test results recorded during head impulses (video head impulse test or scleral coil technique), bithermal caloric testing and rotatory chair testing (sinusoidal stimulation of 0.1 Hz). Vestibular implant (VI) implantation criteria are not the same as diagnostic criteria for bilateral vestibulopathy. The major difference between VI-implantation criteria and the approved diagnostic criteria for BVP are that all included vestibular tests of semicircular canal function (head impulse test, caloric test, and rotatory chair test) need to show significant impairments of vestibular function in the implantation criteria. For this, a two-step paradigm was developed. First, at least one of the vestibular tests needs to fulfill stringent criteria, close to those for BVP. If this is applicable, then the other vestibular tests have to fulfill a second set of criteria which are less stringent than the original criteria for BVP. If the VI-implantation is intended to excite the utricle and/or saccule (otolith stimulation), responses to cervical and ocular vestibular evoked myogenic potentials must be absent in addition to the above mentioned abnormalities of semicircular canal function. Finally, requirements for safe and potentially effective stimulation should be met, including implanting patients with BVP of peripheral origin only, and assessing possible medical and psychiatric contraindications.

Quantifying Eye Alignment in Orbital Fracture Patients: The Digital Hess Screen.

Background: Quantifying diplopia to determine management and track outcomes for orbital fracture patients is vital for standardization between visits, physicians, and coordination among the multiple specialties that manage these patients. However, standardization is challenging, as diplopia is often reported subjectively. This study sought to describe the utility of the digital Hess screen in patients with orbital fractures compared with a control group. Materials and Methods: A prospective pilot study was designed in which adult patients who presented with orbital fractures between November 2017 and January 2019 without prior history of orbital pathology were recruited. Subjects underwent digital Hess screen testing, in which they wore anaglyph glasses and aligned targets on a computer screen to quantify static eye alignment. The degree of any eye misalignment was analyzed and compared with controls. Results: Ninety-one patients and 35 controls were enrolled. All participants were able to complete the digital Hess screen. Average cumulative deviation score of orbital fracture patients within 1 month of injury was 0.65°, compared with 0.28° in controls. This was a statistically significant difference (p < 0.01, 95% confidence interval -0.18 to 0.18). Conclusion: The Hess screen has been used to quantify phoria as a correlate of eye alignment and diplopia, but older versions were cumbersome and difficult to analyze. This study is the first to report on using the digital Hess screen to quantify phoria in orbital fracture patients and provides a more concise and standardized means to track clinical and surgical outcomes of eye alignment.

Fluctuations in Vestibular Afferent Excitability in Menière's Disease.

OBJECTIVE: To determine if Menière's disease is associated with fluctuations in afferent excitability in four human subjects previously implanted with vestibular stimulators. STUDY DESIGN: Longitudinal repeated measures. SETTING: Tertiary referral center, human vestibular research laboratory. PATIENTS: Four human subjects with previously uncontrolled Menière's disease unilaterally implanted in each semicircular canal with a vestibular stimulator. One subject had only two canals implanted. INTERVENTION(S): Repeated measures of electrically-evoked slow phase eye velocity and vestibular electrically-evoked compound action potentials (vECAP) over 2 to 4 years. MAIN OUTCOME MEASURE(S): Slow phase eye velocity and N1-P1 vECAP amplitudes as a function of time. RESULTS: There were statistically significant fluctuations in electrically evoked slow phase eye velocity over time in at least one semicircular canal of each subject. vECAP N1-P1 amplitudes measured at similar time intervals and stimulus intensities seem to show somewhat correlated fluctuations. One of the subjects had a single Menière's attack during this time period. The others did not. CONCLUSIONS: In these four subjects originally diagnosed with Menière's disease, there was fluctuating electrical excitability of the ampullar nerve of at least one canal in each subject. These fluctuations occurred without active symptoms of Menière's disease.

Interactions between Auditory and Vestibular Modalities during Stimulation with a Combined Vestibular and Cochlear Prosthesis.

BACKGROUND: A combined vestibular and cochlear prosthesis may restore hearing and balance to patients who have lost both. To do so, the device should activate each sensory system independently. OBJECTIVES: In this study, we quantify auditory and vestibular interactions during interleaved stimulation with a combined 16-channel cochlear and 6-channel vestibular prosthesis in human subjects with both hearing and vestibular loss. METHODS: Three human subjects were implanted with a combined vestibular and cochlear implant. All subjects had severe-to-profound deafness in the implanted ear. We provided combined stimulation of the cochlear and vestibular arrays and looked for interactions between these separate inputs. Our main outcome measures were electrically evoked slow-phase eye velocities during nystagmus elicited by brief trains of biphasic pulse stimulation of the vestibular end organs with and without concurrent stimulation of the cochlea, and Likert scale assessments of perceived loudness and pitch during stimulation of the cochlea, with and without concurrent stimulation of the vestibular ampullae. RESULTS: All subjects had no auditory sensation resulting from semicircular canal stimulation alone, and no sensation of motion or slow-phase eye movement resulting from cochlear stimulation alone. However, interleaved cochlear stimulation did produce changes in the slow-phase eye velocities elicited by electrical stimulation. Similarly, interleaved semicircular canal stimulation did elicit changes in the perceived pitch and loudness resulting from stimulation at multiple sites in the cochlea. CONCLUSIONS: There are significant interactions between different sensory modalities during stimulation with a combined vestibular and cochlear prosthesis. Such interactions present potential challenges for stimulation strategies to simultaneously restore auditory and vestibular function with such an implant.

Results From a Second-Generation Vestibular Implant in Human Subjects: Diagnosis May Impact Electrical Sensitivity of Vestibular Afferents.

OBJECTIVE: Auditory and vestibular outcomes after placement of a vestibular-cochlear implant in subjects with varying causes of vestibular loss. STUDY DESIGN: Prospective case study. SETTING: Tertiary referral center. PATIENTS: Three human subjects received a vestibular-cochlear implant. Subject 1 had sudden hearing and vestibular loss 10 years before implantation. Subjects 2 and 3 had bilateral Menière's disease with resolution of acute attacks. All subjects had severe-profound deafness in the implanted ear and bilateral vestibular loss. INTERVENTION: Vestibular-cochlear implant with electrode positions confirmed by CT. MAIN OUTCOME MEASURES: Electrically-evoked vestibular and cochlear compound action potentials (ECAPs), speech perception, and electrically-evoked slow-phase eye velocities. RESULTS: Subject 1 had no vestibular ECAP, but normal cochlear ECAPs and cochlear implant function. She had minimal eye-movement with vestibular stimulation. Subject 2 had vestibular ECAPs. This subject had the largest eye velocities from electrical stimulation that we have seen in humans, exceeding 100 degrees per second. Her cochlear implant functions normally. Subject 3 had vestibular and cochlear ECAPs, and robust eye-movements and cochlear implant function. CONCLUSION: The etiology of vestibular loss appears to have a profound impact on sensitivity of vestibular afferents in distinction to cochlear afferents. If this dichotomy is common, it may limit the application of vestibular implants to diagnoses with preserved sensitivity of vestibular afferents. We speculate it is due to differences in topographic organization of Scarpa's versus the spiral ganglion. In two subjects, the second-generation device can produce higher velocity eye movements than seen in the four subjects receiving the first-generation device.

Visual Function, Brain Imaging, and Physiological Factors in Children With Asymmetric Nystagmus due to Chiasmal Gliomas.

PURPOSE: Asymmetric nystagmus can be an important presenting sign of optic pathway gliomas in young children. We investigated the causes of asymmetric nystagmus in children with chiasmal or suprasellar optic pathway gliomas compared with children with similar optic pathway gliomas and stable gaze. METHODS: Longitudinal magnetic resonance imaging before and after treatment, age-corrected visual acuity, ocular examinations, video-oculography, visual evoked potentials, and retinal nerve fiber layer thickness were retrospectively reviewed. RESULTS: Twenty-two children were included (eight with asymmetric nystagmus and 14 with stable gaze). Subjects with asymmetric nystagmus presented at a younger age than those with stable gaze (2.0 vs 5.6 years; P < 0.001). None had neurofibromatosis type 1. Visual acuity, visual evoked potentials, nerve fiber layer, severity of optic atrophy, hydrocephalus, tumor volume, and tumor locations did not differ between those with asymmetric nystagmus and stable gaze. Asymmetric nystagmus resolved shortly after treatment, even though the average visual acuity did not improve. Changes in visual acuity or tumor volume were not different between those with asymmetric nystagmus and stable gaze after treatment. Eye movement recording from two subjects with asymmetric nystagmus revealed an asymmetric pendular-oscillation with vertical components. One subject with stable gaze developed asymmetric nystagmus with tumor growth into the rostral midbrain and associated unilateral vision loss. Another subject with tumor growth into the rostral midbrain acquired vertical saccade dysmetria. CONCLUSION: We hypothesize that asymmetric nystagmus associated with optic pathway gliomas is caused by subclinical abnormalities to retinal axons that connect to gaze holding centers in the rostral midbrain. Direct compression of the rostral midbrain was a possible factor to asymmetric nystagmus in some subjects. However, many subjects with stable gaze also show midbrain compression.

The Dynamics of Prosthetically Elicited Vestibulo-Ocular Reflex Function Across Frequency and Context in the Rhesus Monkey.

Electrical vestibular neurostimulation may be a viable tool for modulating vestibular afferent input to restore vestibular function following injury or disease. To do this, such stimulators must provide afferent input that can be readily interpreted by the central nervous system to accurately represent head motion to drive reflexive behavior. Since vestibular afferents have different galvanic sensitivity, and different natural sensitivities to head rotational velocity and acceleration, and electrical stimulation produces aphysiological synchronous activation of multiple afferents, it is difficult to assign a priori an appropriate transformation between head velocity and acceleration and the properties of the electrical stimulus used to drive vestibular reflex function, i.e., biphasic pulse rate or pulse current amplitude. In order to empirically explore the nature of the transformation between vestibular prosthetic stimulation and vestibular reflex behavior, in Rhesus macaque monkeys we parametrically varied the pulse rate and current amplitude of constant rate and current amplitude pulse trains, and the modulation frequency of sinusoidally modulated pulse trains that were pulse frequency modulated (FM) or current amplitude modulated (AM). In addition, we examined the effects of differential eye position and head position on the observed eye movement responses. We conclude that there is a strong and idiosyncratic, from canal to canal, effect of modulation frequency on the observed eye velocities that are elicited by stimulation. In addition, there is a strong effect of initial eye position and initial head position on the observed responses. These are superimposed on the relationships between pulse frequency or current amplitude and eye velocity that have been shown previously.

Optical Coherence Tomography in Optic Nerve Hypoplasia: Correlation With Optic Disc Diameter, Nerve Fiber Layer Thickness, and Visual Function.

BACKGROUND: The correlation between optic disc diameters (DDs) with average retinal nerve fiber layer thickness (RNFLT) and visual function in children with optic nerve hypoplasia (ONH) having nystagmus is unknown. METHODS: Data were obtained from a retrospective review of 28 children (mean age: 9.4 years; ±5.1). Optic DD was defined as the maximal horizontal opening of Bruch membrane with spectral optical coherence tomography combined with a confocal laser ophthalmoscope. Average RNFLT was obtained from circumpapillary b-scans. RNFLT was also remeasured at eccentricities that were proportionate with DD to rule out potential sampling artifacts. Visual function was assessed by visual acuity at last follow-up and by visual evoked potentials (VEP) in 11 patients. The eye with the larger DD, which had better visual acuity, was analyzed to exclude potential effects of amblyopia. RESULTS: DD was correlated with average RNFLT (r = 0.61), visual acuity (r = 0.32), and VEPs (r = 0.66). The relationship between RNFLT and DD was as follows: average RNFLT (µm) = 0.074 * DD (µm) - 18.8. RNFLT also correlated with the ratio of horizontal optic DD to macula-disc-margin distance (DD:DM; r = 0.59). RNFLT measured at eccentricities proportionate with DD showed progressive decrease in thickness only for DDs <1,100 µm. All patients with DD <1,000 µm had subnormal visual acuity, whereas those with DD <1,200 µm had subnormal VEPs. CONCLUSIONS: DD correlates with average RNFLT and with visual function in children with ONH. Using OCT imaging, DD can be obtained in children with nystagmus and provides objective information.

Does eye velocity due to infantile nystagmus deprive visual acuity development?

PURPOSE: To use eye movement recordings of young children to determine whether eye velocity from infantile nystagmus (IN) deprives the developing visual system of normal visual acuity. METHODS: The video-oculography recordings and visual acuity measurements (including Teller cards) of 15 children ≤6.0 years of age with IN without visual sensory disease (idiopathic IN) were reviewed retrospectively. Eye velocity that would limit visual acuity development was predicted from both empirical adult data adjusted for age and a temporal limitation model using published photoreceptor density data with age. Foveal alignment onto a target was measured in 5 subjects using confocal retinal imaging. RESULTS: All subjects had periods (85-2440 ms) during which eye velocity was below the limit that would reduce age-appropriate visual acuity. The percentage of time eye velocity was below the limit varied by 4%-54% across all eye movement recordings. Eye movement metrics (eye position variability, average eye velocity, maximum duration of foveation, and the nystagmus optimal foveation fraction) correlated poorly with age or with age-corrected visual acuity (r2 < 0.27 for each metric). Longitudinal visual acuity development overlapped between subjects with different nystagmus waveforms. CONCLUSIONS: Eye velocity was not predicted to completely deprive visual acuity development in subjects with idiopathic IN. Nystagmus may decrease visual acuity development in children with idiopathic IN by interfering with visual-cortical development in the context of increased visual noise due to image motion with imprecise foveation.

The relationship of nystagmus waveform on the VEP response in infantile nystagmus syndrome: a small case series.

PURPOSE: The relationship between eye movements and the visual evoked potential (VEP) response was examined in two subjects with infantile nystagmus syndrome (INS). Changes in VEP amplitude were compared between periods of foveation versus periods of high-frequency nystagmus. An analysis is proposed that improves extraction of the checkerboard reversal VEP signal from subjects with INS. METHODS: INS subjects were 2 healthy children (12-13 years old) with 20/40 or better corrected acuity. Optical coherence tomography confirmed the optic nerves, retina, and fovea were within normal variation. VEPs were recorded to checkerboard reversal and to onset/offset of horizontal gratings while simultaneously recording the electrooculogram (EOG). VEP epochs underwent Fourier analysis, and epochs were examined for phase consistency with the mean. Foveation periods were compared to video-oculography recordings from a separate session. RESULTS: Optic nerve misrouting, such as crossed VEP asymmetry seen in albinism, or ipsilateral VEP asymmetry seen in achiasma, was not detected in either subject. By averaging only epochs in which EOG epochs showed foveation, VEP amplitude could be increased ≥59%. Averaging the VEP only on epochs with consistent phase at Oz increased VEP amplitude by ≥twofold; subsequent EOG epochs after this analysis mostly contained foveation periods or minimal EOG activity. Latency varied <14 ms across all analyses. CONCLUSIONS: The checkerboard reversal VEP signal is dependent on foveation periods in subjects with INS despite good visual acuity. Reduction in VEP amplitude due to retinal image motion induces noise and/or lack of phase locking in the VEP epochs. Selective averaging of epochs based on phase consistency improves the extraction of a VEP signal, likely when retinal image motion is minimized.