Comparison of adaptation characteristics between visually- and memory-guided saccades.

Saccade adaptation plays a crucial role in maintaining saccade accuracy. The behavioral characteristics and neural mechanisms of saccade adaptation for an externally cued movement, such as visually-guided saccades (VGS), are well studied in non-human primates. In contrast, little is known about the saccade adaptation of an internally driven movement, such as memory-guided saccades (MGS), which are guided by visuospatial working memory. As the oculomotor plant changes due to growth, aging, or skeletomuscular problems, both types of saccades need to be adapted. Do both saccade types engage a common adaptation mechanism? In this study, we compared the characteristics of amplitude decrease adaptation in MGS with VGS in non-human primates. We found that the adaptation speed was faster for MGS than for VGS. Saccade duration changed during MGS adaptation, while saccade peak velocity changed during VGS adaptation. We also compared the adaptation field, that is, the gain change for saccade amplitudes other than the adapted. The gain change for MGS declines on both smaller and larger sides of adapted amplitude, more rapidly for larger than smaller amplitudes, while the decline in VGS was reversed. Thus, the differences between VGS and MGS adaptation characteristics support the previously suggested hypothesis that the adaptation mechanisms of VGS and MGS are distinct. Furthermore, the result suggests that the MGS adaptation site is a brain structure that influences saccade duration, while the VGS adaptation site influences saccade peak velocity. These results should be beneficial for future neurophysiological experiments.

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.

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.

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.

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.

VEP analysis methods in children with optic nerve hypoplasia: relationship to visual acuity and optic disc diameter.

PURPOSE: Assessing vision in young children with optic nerve hypoplasia (ONH) is challenging due to multi-directional infantile nystagmus, the range of optic nerve loss, and cognitive delay. This study examined visual evoked potential (VEP) responses and averaging techniques in children with ONH. The assumption is that EEG epochs with inconsistent temporal phase would be associated with nystagmus, signal reduction due to axon loss, and visual inattention. METHODS: A retrospective chart review was performed on 44 children (average age 2.2 years; SD 1.9). Optic disc diameter was estimated by ophthalmoscopy. Visual function was measured under binocular viewing and then compared to the eye with the larger optic disc to exclude secondary amblyopia. Visual acuity was measured by Teller cards or by recognition optotypes, and both measures were converted into log minimum angle of resolution (logMAR). VEPs were recorded to onset/offset of horizontal gratings and to reversing checkerboards. Signal-to-noise ratios (SNRs) were estimated from phase consistency across epochs in the Fourier domain. VEPs were also averaged after (1) correction of epochs for phase shifts across a limited bandwidth, or (2) selection of only epochs showing phase consistency. RESULTS: Optic disc diameter, logMAR, VEP amplitudes, and VEP SNR were all significantly inter-correlated. Optic disc diameter correlated best with VEP SNR (Spearman rho = 0.82; p < 0.001). Age-corrected logMAR correlated with optic disc diameter and VEP SNR (Spearman rho = -0.695 and 0.70, respectively; p < 0.001). VEP latency poorly correlated with optic disc diameter or logMAR. Correction of phase shifts or selection of epochs based on phase consistency significantly increased VEP amplitude and SNR for children with optic disc diameters <1000 microns. Correction of phase inconsistency did not improve the correlation of VEP parameters with optic disc diameter or with logMAR. CONCLUSIONS: In ONH, the size of the optic nerve is correlated with VEP SNR and logMAR. The results imply a direct relationship between the reduction in optic nerve axons and generalized reduction in visual function. Our calculation of VEP SNR provides objective assessment of optic nerve function that is independent of subjective scoring of VEP peaks.

Vestibular implantation and longitudinal electrical stimulation of the semicircular canal afferents in human subjects.

Animal experiments and limited data in humans suggest that electrical stimulation of the vestibular end organs could be used to treat loss of vestibular function. In this paper we demonstrate that canal-specific two-dimensionally (2D) measured eye velocities are elicited from intermittent brief 2 s biphasic pulse electrical stimulation in four human subjects implanted with a vestibular prosthesis. The 2D measured direction of the slow phase eye movements changed with the canal stimulated. Increasing pulse current over a 0-400 µA range typically produced a monotonic increase in slow phase eye velocity. The responses decremented or in some cases fluctuated over time in most implanted canals but could be partially restored by changing the return path of the stimulation current. Implantation of the device in Meniere's patients produced hearing and vestibular loss in the implanted ear. Electrical stimulation was well tolerated, producing no sensation of pain, nausea, or auditory percept with stimulation that elicited robust eye movements. There were changes in slow phase eye velocity with current and over time, and changes in electrically evoked compound action potentials produced by stimulation and recorded with the implanted device. Perceived rotation in subjects was consistent with the slow phase eye movements in direction and scaled with stimulation current in magnitude. These results suggest that electrical stimulation of the vestibular end organ in human subjects provided controlled vestibular inputs over time, but in Meniere's patients this apparently came at the cost of hearing and vestibular function in the implanted ear.

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.

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.

Anatomic features and function of the macula and outcome of surgical tenotomy and reattachment in achiasma.

OBJECTIVE: To examine the anatomic features and function of the macula in achiasma and to compare visual acuity, eye movements, foveation, and eye velocity before and after tenotomy and reattachment (T&R) surgery. DESIGN: Case series. PARTICIPANTS: Two children with isolated achiasma. METHODS: Ophthalmologic examinations, brain magnetic resonance imaging, full-field and multifocal electroretinography (ERG), visual evoked potentials (VEPs), spectral-domain optical coherence tomography (OCT), eye-movement recordings, and unilateral T&R in 1 patient. MAIN OUTCOME MEASURES: Visual acuity before and after surgery, macular anatomic features and function, and eye velocity before and after T&R surgery in 1 patient. RESULTS: Magnetic resonance imaging and VEP confirmed absence of decussation of retinofugal fibers in both patients. Visual acuity was 20/100 and 20/200. The anatomic features and function of the fovea and macula were normal by OCT and multifocal ERG. After T&R, there was a marked reduction in horizontal eye velocity and monocular visual acuity improved to 20/80. CONCLUSIONS: The finding that the macula is normal in achiasma suggests that reduced acuity is the result of retinal image motion from nystagmus. Two-muscle T&R reduces horizontal retinal image motion and can improve visual acuity in achiasma or patients with infantile nystagmus.

Persistent figure-eight and side-to-side head shaking is a marker for rhombencephalosynapsis.

BACKGROUND: Head-shaking stereotypies have been described in patients with neurological impairment. We noted an unusual preponderance of head shaking in patients with rhombencephalosynapsis (RES). We sought to delineate the movements further and determine whether oculomotor and vestibular testing could reveal their cause. METHODS: Information was collected from direct observation, video review and parental questionnaire from 59 patients with RES. Oculomotor and vestibular testing was performed in 4 children. RESULTS: Of 59 patients, 50 had persistent head shaking that was often observed years before RES was recognized. Three affected children demonstrated abnormal central vestibular processing. CONCLUSIONS: Head-shaking is common in RES. These characteristic movements may provide input to a defective vestibular system or may represent a motor pattern that is usually suppressed by vestibular feedback. Persistent head shaking should alert clinicians to the possible presence of a congenital hindbrain abnormality that affects the vestibulocerebellum, particularly RES.

Postural responses to electrical stimulation of the vestibular end organs in human subjects.

A multichannel vestibular prosthesis that delivers electrical stimulation to the perilymph of individual semicircular canals is a potential new treatment modality for patients with vestibular deficiencies. Most research in this field has evaluated the efficacy of this approach by its ability to reproduce eye movements in response to head rotations. Our group has developed such a device and implanted it in four human subjects with intractable unilateral Meniere's disease. This allows us to evaluate individual semicircular canal contribution to the control of balance and posture in human subjects. In this report, we demonstrate that electrical stimulation trains delivered to the perilymph of individual semicircular canals elicit postural responses specific to the particular canal stimulated, with some current spread to adjacent end organs. Modulation of stimulation current modulates the amplitude of the postural response. However, eye movements elicited by the same electrical stimuli were not consistent with postural responses in magnitude or direction in all subjects. Taken together, these findings support the feasibility of a vestibular prosthesis for the control of balance and illustrate new challenges for the development of this technology.

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.

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.

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.

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.

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.

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.

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.