Utilization of Ophthalmic Management in Patients with Head-and-Neck Trauma Secondary to Firearms.

Introduction: This retrospective cohort study presents the epidemiology of severe firearm-related ophthalmic injury and the level of ophthalmology involvement in the multidisciplinary management of head-and-neck gunshot injuries. Methods: A retrospective study identified 207 patients with firearm-related injuries involving the head and neck treated at an Academic Tertiary Care Institution from 2010 to 2020. Results: Ophthalmology consulted on 29% of patients with head-and-neck firearm injuries. At least one of the services managing facial trauma (plastic surgery and otolaryngology) consulted on 71.5% of cases (P < 0.001). Of patients evaluated by ophthalmology, 93.3% survived to discharge; 78.2% of patients who were not evaluated survived to discharge (P = 0.009). Ophthalmology consulted on all patients with open globe injury (10.6%) (P < 0.001), all of which were evaluated by the facial trauma service (P = 0.002), 77.3% by otolaryngology (P = 0.42), 50% by neurosurgery, 36.4% by plastic surgery, 13.6% by orthopedic surgery, and 4.5% by vascular surgery. Ophthalmology consulted on 76.5% of patients with orbital fracture (32.9%) (P < 0.001); 83.8% were evaluated by the facial trauma service (P = 0.006), 69.1% by otolaryngology (P = 0.014), 54.4% by neurosurgery, 27.9% by plastic surgery, 10.3% by orthopedic surgery, and 2.9% by vascular surgery. For patients with orbital fractures, 92.3% survived when ophthalmology was consulted (P = 0.698); 43.8% survived when not consulted (P = 0.001). Conclusions: Firearm-related injuries of the head and neck frequently involve ocular and orbital structures, often causing serious vision-threatening injuries. Multispecialty management is common and early ophthalmology specialist evaluation and co-management are indicated to best identify ophthalmic injuries.

Lesion-induced sprouting promotes neurophysiological integration of septal and entorhinal inputs to granule cells in the dentate gyrus of rats.

Axonal sprouting of dentate gyrus (DG) afferents after entorhinal cortex (EC) lesion is a model preparation to assess lesion-induced functional reorganization in a denervated target structure. Following a unilateral EC lesion, the surviving contralateral entorhinal projection, termed the crossed temporodentate pathway (CTD), and the heterotypic septal input to the DG, the septodentate pathway (SD), undergo extensive axonal sprouting. We explored whether EC lesion alters the capacity of the SD pathway to influence CTD-evoked granule cell excitability in the DG. We recorded extracellular field excitatory postsynaptic potentials (fEPSPs) after CTD stimulation alone and paired SD-CTD stimulation. Male rats were given unilateral EC lesions or sham operations; evoked fEPSPs in the DG were recorded at 4-, 15-, and 90-days post-entorhinal lesion to assess functional reorganization of the CTD and SD pathways. We found significantly increased fEPSP amplitudes in cases with unilateral lesions compared to sham-operates at 15- and 90-days post lesion. Within each time point, paired SD-CTD stimulation resulted in significantly depressed fEPSP amplitudes compared to amplitudes evoked after CTD stimulation alone and this effect was solely seen in cases with EC lesion. In cases where granule cell discharge was observed, SD stimulation increased discharge amplitude elicited by the CTD stimulation at 90-days postlesion. These findings demonstrate that synaptic remodeling following unilateral cortical lesion results in a synergistic interaction between two established hippocampal afferents that is not seen in uninjured brains. This work may be important for models of neurodegenerative disease and neural injury that target these structures and associated hippocampal circuitry.

Ocular adnexal phenotype and management of a patient with mosaic expression of a mutation in TWIST2.

Ablepharon-macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are congenital ectodermal dysplasias associated with mutations in the TWIST2 gene. Among the ophthalmic anomalies that occur in these syndromes, underdevelopment of the anterior lamella of the eyelid is a defining feature. Reports of mosaic expression of TWIST2 mutations are extremely rare, with only five confirmed or suspected cases described to date. Mosaic expression of TWIST2 variants is correlated with a less severe phenotype than that reported for the typical expression of TWIST2 variants associated with BSS or AMS. Abnormal development of the anterior lamella appears to be a common feature in all cases of AMS with mosaic expression. Here, we describe the phenotype of a patient with mosaic expression of a TWIST2 mutation that is typically associated with AMS. We additionally describe the surgical approach employed in the treatment of this patient.

Blunderbuss: Ocular and Orbital Injuries Due to Muzzle-Loading Firearms.

PURPOSE: Injury to the eye and/or orbital and adnexal structures associated with antiquated muzzle-loading firearms has not, to our knowledge, been characterized with the exception of a single case report. METHODS: A retrospective chart review of 7 patients treated at Vanderbilt University Medical Center from 2003 to 2017 who sustained traumatic injuries to the ocular and/or orbital structures secondary to the discharge of muzzle-loading firearms. The study was approved by the Vanderbilt Institutional Review Board. RESULTS: In 6/7 cases, injuries occurred secondary to the muzzle-loading firearm exploding due to dysfunction or misuse. Foreign material deriving from the firearm was retained in 3/7 patients. Initial examination of the orbit and adnexa revealed 5/7 individuals sustaining orbital fractures and 6/7 with facial lacerations (including 2 with eyelid lacerations); none had evidence of a lacrimal duct injury. Three patients suffered globe injuries (1 closed-globe and 2 open-globe). Visual acuity at last follow-up was ≥20/20 in 12/14 eyes examined. Surgical intervention was required in the treatment of 4/7 individuals (including 3/7 requiring intervention for sustained orbital fractures). No individuals were wearing eye protection at the time of injury. All individuals survived their injuries. CONCLUSIONS: The operation of muzzle-loading firearms poses a unique risk of injury to the operator. The resultant injuries in this case series were primarily due to the explosion of the firearm, which subsequently appear similar to orbital and ocular blast injuries caused by explosive weapons. Orbital injuries and more potentially more devastating ocular injuries may have been prevented by protective eyewear.

Factors Affecting Repeatability of Foveal Avascular Zone Measurement Using Optical Coherence Tomography Angiography in Pathologic Eyes.

PURPOSE: To determine factors that may affect the repeatability of the foveal avascular zone (FAZ) measurement obtained using optical coherence tomography angiography (OCTA) including instrument type, image segmentation, image quality, and fundus pathology. PATIENTS AND METHODS: This prospective single-center study enrolled 43 subjects (85 eyes) with retinal vasculopathy, macular edema, optic pathology or normal contralateral eye. The macula was imaged twice using Optovue Angiovue and once using Cirrus Angioplex to obtain 3x3mm OCTA images centered on the fovea. Images were generated by the same operator within 30 mins. The FAZ size for the entire retinal thickness ("overall FAZ") was measured automatically using the OCTA software. The FAZ size of the superficial and deep retinal vascular plexus layers was measured manually using the enface OCTA images of the segmented layers and Image J analysis. Intraclass correlations coefficient (ICC) was calculated to determine repeatability. RESULTS: For the overall FAZ measurement, repeatability was excellent (ICC 0.953 right eye, 0.938, left eye) using the same machine (intra-instrument) and somewhat lower but still good to excellent (ICC 0.803 right eye, 0.917 left eye) using machines made by different vendors (inter-instrument). For the segmented layers, intra-instrument repeatability of FAZ measurement was excellent (ICC > 0.95) for both plexus layers. Inter-instrument repeatability was good for the superficial plexus layer (ICC 0.86 right eye, 0.88 left eye) but reduced for the deep plexus layer (ICC 0.63 right eye, 0.57 left eye). Suboptimal image quality and presence of retinal vasculopathy and macular edema tended to reduce FAZ repeatability but to a lesser degree. CONCLUSION: Inter- and intra-instrument repeatability of the overall FAZ measurement was high using commercial OCTA instruments and only mildly reduced by suboptimal image quality and fundus pathology. For segmented layers, intra-instrument repeatability remained high but inter-instrument repeatability was reduced for the deep plexus layer.

Blastic Transformation of a Mantle Cell Lymphoma Presenting as an Enlarging Unilateral Orbital Mass.

Mantle cell lymphoma (MCL) is an uncommon form of non-Hodgkin lymphoma predominantly affecting male individuals of advanced age. Approximately 1-9% of cases of lymphoma affecting the orbital and ocular adnexal regions are attributed to MCL. We describe the case of a 65-year-old man with a 24-year history of MCL with initial remission followed by multiple relapses who presented with acute-onset binocular diplopia and proptosis of the left eye. Subsequent imaging demonstrated a new left superior orbital mass. Biopsy of the mass revealed two clonally related, yet distinct cellular components demonstrating the classical mantle cell morphology and large cells that appeared to have transformed to the blastoid variant of MCL. Transformation of classical MCL to the blastoid variant of MCL is rare, with few reports in the literature. The blastoid variant of MCL tends to be aggressive and associated with a poor prognosis. The case we describe represents perhaps the first report of MCL transformation observed in the orbit.

Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome.

A 4 year-old-boy was referred for distichiasis of the upper and lower lids of both eyes that had been present since at least 1 year of age. The patient's family history was notable for distichiasis and lymphedema affecting numerous family members. The patient was found to have a novel heterozygous variant (c.741_742insGG) in the FOXC2 gene. Mutations in the FOXC2 gene are associated with lymphedema-distichiasis syndrome. An important feature of lymphedema-distichiasis syndrome is that distichiasis is typically present prior to the onset of lymphedema.

Perceptual training enhances temporal acuity for multisensory speech.

The temporal relationship between auditory and visual cues is a fundamental feature in the determination of whether these signals will be integrated. The window of perceived simultaneity (TBW) is a construct that describes the epoch of time during which asynchronous auditory and visual stimuli are likely to be perceptually bound. Recently, a number of studies have demonstrated the capacity for perceptual training to enhance temporal acuity for audiovisual stimuli (i.e., narrow the TBW). These studies, however, have only examined multisensory perceptual learning that develops in response to feedback that is provided when making judgments on simple, low-level audiovisual stimuli (i.e., flashes and beeps). Here we sought to determine if perceptual training was capable of altering temporal acuity for audiovisual speech. Furthermore, we also explored whether perceptual training with simple or complex audiovisual stimuli generalized across levels of stimulus complexity. Using a simultaneity judgment (SJ) task, we measured individuals' temporal acuity (as estimated by the TBW) prior to, immediately following, and one week after four consecutive days of perceptual training. We report that temporal acuity for audiovisual speech stimuli is enhanced following perceptual training using speech stimuli. Additionally, we find that changes in temporal acuity following perceptual training do not generalize across the levels of stimulus complexity in this study. Overall, the results suggest that perceptual training is capable of enhancing temporal acuity for audiovisual speech in adults, and that the dynamics of the changes in temporal acuity following perceptual training differ between simple audiovisual stimuli and more complex audiovisual speech stimuli.

The Impact of Feedback on the Different Time Courses of Multisensory Temporal Recalibration.

The capacity to rapidly adjust perceptual representations confers a fundamental advantage when confronted with a constantly changing world. Unexplored is how feedback regarding sensory judgments (top-down factors) interacts with sensory statistics (bottom-up factors) to drive long- and short-term recalibration of multisensory perceptual representations. Here, we examined the time course of both cumulative and rapid temporal perceptual recalibration for individuals completing an audiovisual simultaneity judgment task in which they were provided with varying degrees of feedback. We find that in the presence of feedback (as opposed to simple sensory exposure) temporal recalibration is more robust. Additionally, differential time courses are seen for cumulative and rapid recalibration dependent upon the nature of the feedback provided. Whereas cumulative recalibration effects relied more heavily on feedback that informs (i.e., negative feedback) rather than confirms (i.e., positive feedback) the judgment, rapid recalibration shows the opposite tendency. Furthermore, differential effects on rapid and cumulative recalibration were seen when the reliability of feedback was altered. Collectively, our findings illustrate that feedback signals promote and sustain audiovisual recalibration over the course of cumulative learning and enhance rapid trial-to-trial learning. Furthermore, given the differential effects seen for cumulative and rapid recalibration, these processes may function via distinct mechanisms.

Atypical rapid audio-visual temporal recalibration in autism spectrum disorders.

Changes in sensory and multisensory function are increasingly recognized as a common phenotypic characteristic of Autism Spectrum Disorders (ASD). Furthermore, much recent evidence suggests that sensory disturbances likely play an important role in contributing to social communication weaknesses-one of the core diagnostic features of ASD. An established sensory disturbance observed in ASD is reduced audiovisual temporal acuity. In the current study, we substantially extend these explorations of multisensory temporal function within the framework that an inability to rapidly recalibrate to changes in audiovisual temporal relations may play an important and under-recognized role in ASD. In the paradigm, we present ASD and typically developing (TD) children and adolescents with asynchronous audiovisual stimuli of varying levels of complexity and ask them to perform a simultaneity judgment (SJ). In the critical analysis, we test audiovisual temporal processing on trial t as a condition of trial t - 1. The results demonstrate that individuals with ASD fail to rapidly recalibrate to audiovisual asynchronies in an equivalent manner to their TD counterparts for simple and non-linguistic stimuli (i.e., flashes and beeps, hand-held tools), but exhibit comparable rapid recalibration for speech stimuli. These results are discussed in terms of prior work showing a speech-specific deficit in audiovisual temporal function in ASD, and in light of current theories of autism focusing on sensory noise and stability of perceptual representations. Autism Res 2017, 10: 121-129. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan.

Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations.

Multisensory perceptual learning is dependent upon task difficulty.

There has been a growing interest in developing behavioral tasks to enhance temporal acuity as recent findings have demonstrated changes in temporal processing in a number of clinical conditions. Prior research has demonstrated that perceptual training can enhance temporal acuity both within and across different sensory modalities. Although certain forms of unisensory perceptual learning have been shown to be dependent upon task difficulty, this relationship has not been explored for multisensory learning. The present study sought to determine the effects of task difficulty on multisensory perceptual learning. Prior to and following a single training session, participants completed a simultaneity judgment (SJ) task, which required them to judge whether a visual stimulus (flash) and auditory stimulus (beep) presented in synchrony or at various stimulus onset asynchronies (SOAs) occurred synchronously or asynchronously. During the training session, participants completed the same SJ task but received feedback regarding the accuracy of their responses. Participants were randomly assigned to one of three levels of difficulty during training: easy, moderate, and hard, which were distinguished based on the SOAs used during training. We report that only the most difficult (i.e., hard) training protocol enhanced temporal acuity. We conclude that perceptual training protocols for enhancing multisensory temporal acuity may be optimized by employing audiovisual stimuli for which it is difficult to discriminate temporal synchrony from asynchrony.

Deficient proactive interference of eyeblink conditioning in Wistar-Kyoto rats.

Wistar-Kyoto (WKY) rats exhibit behavioral inhibition and model anxiety vulnerability. Although WKY rats exhibit faster active avoidance acquisition, simple associative learning or the influence of proactive interference (PI) has not been adequately assessed in this strain. Therefore, we assessed eyeblink conditioning and PI in WKY and outbred Sprague-Dawley (SD) rats. Rats were pre-exposed to either the experimental context, the conditioned stimulus (CS), the unconditional stimulus (US), or the CS & US in an explicitly unpaired (EUP) manner, to examine latent inhibition (LI), US pre-exposure effect, or learned irrelevance (LIRR), respectively. Immediately following pre-exposures, rats were trained in a delay-type paradigm (500 ms CS coterminating with a 10-ms US) for one session. During training SD rats exhibited LI and inhibition from US pre-exposures without evidence of LIRR. PI was less evident in WKY rats; LI was absent in WKY rats. Even in the context of reduced PI to CS-alone and US-alone pre-exposures, LIRR was not apparent in WKY rats. The more normal acquisition rates exhibited by WKY rats, under conditions which degrade performance in SD rats, increases the overall likelihood for WKY rats to acquire defensive responses. Enhanced acquisition of defensive responses is a means by which anxiety vulnerability (e.g., behavioral inhibition) is translated to anxiety psychopathology.