Fusion Range Research Articles

A Cross-Sectional Study on Visual Problems among Zari Artisans of North India

Background: Working circumstances of the zardozi workers, it is highly likely that they develop visual problems that may range from simple asthenopic symptoms to severe visual disturbances. The present study was done to assess the visual problems existing today among zari artisans of North India. Materials and Methods: Two hundred and forty zari artisans were clinically examined during January 2022 to May 2022. All the patients were subjected to an ocular evaluation: Visual acuity, anterior segment evaluation, orthoptic evaluation with prism bars Goldmann Applanation tonometry, fundus examination, and refractive status of the patients. Means and proportions were calculated. The Chi-square test was applied. P < 0.05 is considered to be significant. Results: The mean age of the study population was 27 ± 12 years; majority of which were males, making up to 80.83% of the study population. Most of the subjects fell into the age group of 21–30 years. On testing the refractive error in them, we found 43.33% of the study subjects were hypermetropic, 35.00% were myopic, and 21.67% were emmetropic. Around 45% had poor convergence status while 26.67% had fatigue of convergence and 28.75% had fair convergence. A significant association was found between the positive fusional range and convergence status of the study subjects (P < 0.001). Conclusion: Adequate lighting conditions, proper ventilation and hygiene, short breaks in between, proper nutrition, correction of refractive error if any, and periodic regular eye checkup should be done to overcome these visual problems in Zardozi artisans.

Anomalous head posture

Intermittent exotropia (IXT) usually presents with occasional outward deviation of the eye, asthenopia, headache, diplopia, or photophobia. We report here an unusual presentation of IXT in a 21-year-old man, with an anomalous head posture (AHP) of face rotation towards left as the primary symptom. On examination, there was lateral gaze incomitance, and improved fusion range in dextroversion explained his AHP.

Getting Your Laboratory on Track With Neurotrophic Receptor Tyrosine Kinase.

Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration-approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making. However, the testing landscape for NTRK fusions is complex, and optimal testing depends on the clinicopathologic scenario. To compare different NTRK testing methods to help pathologists understand test features and performance characteristics and make appropriate selections for NTRK fusion detection for their laboratory and individual patient specimens. A literature search for NTRK gene fusions and TRK protein was performed, including papers that discussed treatment, testing methodology, and detection or prevalence of fusion-positive cases. As standard of care in some tumor types, next-generation sequencing (NGS) panel testing is a cost effective and reliable way to detect a broad range of NTRK fusions. The design of the panel and use of DNA or RNA will affect performance characteristics. Pan-TRK immunohistochemistry may be used as a rapid, less expensive screen in cases that will not undergo routine NGS testing, or on specimens unsuitable for NGS testing. Fluorescence in situ hybridization may be appropriate for low-tumor-content specimens that are unsuitable for NGS testing. Quantitative reverse transcription polymerase chain reaction is best suited for monitoring low-level disease of a specific, previously identified target. This information should help laboratories develop a laboratory-specific NTRK testing algorithm that best suits their practice setting and patients' needs.

Comparison of Measured Fusional Vergence Amplitudes using Prism Bar and Synoptophore in Sudanese Patients with Near Exophoria

Background: Assessment of the fusional vergence amplitudes constitutes one of the most important diagnostic tools to obtain information about the ability to maintain binocular vision. Several techniques can be used to assess this function. However, those methods are not interchangeable, and the measurement repeatability has been questioned. Objective: This study aimed to compare fusional vergence range measurements using prism bars and synoptophore in Sudanese patients with near exophoria Methods: The study was a comparative cross-sectional hospital-based, performed in the binocular vision clinic at the Al-Neelain Eye Hospital. Fusional vergence amplitudes (positive and negative) were measured on 122 patients (67 females and 55 males), and the mean age and standard deviation were 16.79 ± 5.22 years old using prism bar and synoptophore methods. Results: The findings showed that the higher positive fusional vergence was obtained using the synoptophore method (24.7 ± 7.2 Δ base-out), whereas the prism bar method provided the lower finding (22.6± 7.6 Δ base-out). Conversely, the prism bar method revealed a higher measurement for negative fusional vergence (13.9± 3.9 Δ base-in) than the synoptophore method (12.7± 3.7 Δ base-in). Using the t-test, significant differences were found between all measurements with the two techniques, P<0.05. Measurements of positive and negative fusional vergence amplitudes by the two methods showed no relationship between age and fusional vergence, P>0.05. Conclusion: Given the significant difference in the results obtained between the two methods for measuring the positive and negative fusional vergence amplitudes, caution should be taken when making decisions regarding fusional vergence assessment in patients with latent and manifest strabismus.

Factors underlying masking release by voice-gender differences and spatial separation cues in multi-talker listening environments in listeners with and without hearing loss.

Voice-gender differences and spatial separation are important cues for auditory object segregation. The goal of this study was to investigate the relationship of voice-gender difference benefit to the breadth of binaural pitch fusion, the perceptual integration of dichotic stimuli that evoke different pitches across ears, and the relationship of spatial separation benefit to localization acuity, the ability to identify the direction of a sound source. Twelve bilateral hearing aid (HA) users (age from 30 to 75 years) and eleven normal hearing (NH) listeners (age from 36 to 67 years) were tested in the following three experiments. First, speech-on-speech masking performance was measured as the threshold target-to-masker ratio (TMR) needed to understand a target talker in the presence of either same- or different-gender masker talkers. These target-masker gender combinations were tested with two spatial configurations (maskers co-located or 60° symmetrically spatially separated from the target) in both monaural and binaural listening conditions. Second, binaural pitch fusion range measurements were conducted using harmonic tone complexes around a 200-Hz fundamental frequency. Third, absolute localization acuity was measured using broadband (125-8000 Hz) noise and one-third octave noise bands centered at 500 and 3000 Hz. Voice-gender differences between target and maskers improved TMR thresholds for both listener groups in the binaural condition as well as both monaural (left ear and right ear) conditions, with greater benefit in co-located than spatially separated conditions. Voice-gender difference benefit was correlated with the breadth of binaural pitch fusion in the binaural condition, but not the monaural conditions, ruling out a role of monaural abilities in the relationship between binaural fusion and voice-gender difference benefits. Spatial separation benefit was not significantly correlated with absolute localization acuity. In addition, greater spatial separation benefit was observed in NH listeners than in bilateral HA users, indicating a decreased ability of HA users to benefit from spatial release from masking (SRM). These findings suggest that sharp binaural pitch fusion may be important for maximal speech perception in multi-talker environments for both NH listeners and bilateral HA users.

Chromatin Accessibility Landscapes of B-Cell Acute Lymphoblastic Leukemia Identify Extensive Epigenomic Reprogramming and Heterogeneity Among Subtypes

Acute lymphoblastic leukemia (ALL) is the most common malignancy in pediatric patients and represents about a quarter of all pediatric malignancies. Past work has characterized B-cell lineage ALL (B-ALL) into molecular subtypes spanning a range of aberrant chromosomal rearrangements and oncogene chimeric fusions driving malignancy. While transcriptional and DNA methylome profiling of these subtypes has been extensively examined, the accompanying chromatin landscape and corresponding gene regulatory repertoire are not well characterized for many B-ALL subtypes. To better profile the B-ALL epigenome and gene regulatory networks we examined chromatin accessibility of 11 distinct molecular subtypes (BCR-ABL1, DUX4/ERG, ETV6-RUNX1, Hyperdiploid, Low hypodiploid, KMT2A-rearranged, Ph-like, PAX5-altered, TCF3-PBX1, ZNF384-rearranged and B-other) using 154 primary patient samples from across the United States with assay for transposase-accessible chromatin and high-throughput sequencing (ATAC-seq). We mapped extensive chromatin reprogramming when comparing B-ALL and normal B-cells that drive oncogenic signaling pathways and inhibit normal B-cell functions. Strikingly, we also uncovered chromatin accessibility sites in B-ALL (42,457 sites) with distinct subtype-specific enrichment. A classification model utilizing subtype distinct loci was able to accurately predict B-ALL subtypes with 87% cross-validation accuracy. Transcription factor (TF) footprint profiling and transcriptomic information further identified candidate subtype-enriched TFs, such as DUX4, ZNF384, HOXA9, MEIS1, GATA3 and RARA, along with subtype distinct gene regulatory networks. In connecting these findings with genetic variation, we identified 9080 inherited DNA sequence variants that act as ATAC-seq chromatin accessibility quantitative trait loci (ATAC-QTLs) and contribute to variability in chromatin accessibility among patient samples. Nearly one-third of ATAC-QTLs map to TF footprints and commonly altered DNA consensus motifs impacting chromatin accessibility include ETS family TFs (PU.1, SPI-B, ELF3, EHF), ZNF family (ZNF263, ZNF460) and CTCF. Collectively, using the largest B-ALL chromatin accessibility dataset to date, our investigation offers a unique window into the gene regulatory landscape that highlights the complexity and heterogeneity of chromatin accessibility among B-ALL molecular subtypes.

Differential Effects of Binaural Pitch Fusion Range on the Benefits of Voice Gender Differences in a "Cocktail Party" Environment for Bimodal and Bilateral Cochlear Implant Users.

Some cochlear implant (CI) users are fitted with a CI in each ear ("bilateral"), while others have a CI in one ear and a hearing aid in the other ("bimodal"). Presently, evaluation of the benefits of bilateral or bimodal CI fitting does not take into account the integration of frequency information across the ears. This study tests the hypothesis that CI listeners, especially bimodal CI users, with a more precise integration of frequency information across ears ("sharp binaural pitch fusion") will derive greater benefit from voice gender differences in a multi-talker listening environment. Twelve bimodal CI users and twelve bilateral CI users participated. First, binaural pitch fusion ranges were measured using the simultaneous, dichotic presentation of reference and comparison stimuli (electric pulse trains for CI ears and acoustic tones for HA ears) in opposite ears, with reference stimuli fixed and comparison stimuli varied in frequency/electrode to find the range perceived as a single sound. Direct electrical stimulation was used in implanted ears through the research interface, which allowed selective stimulation of one electrode at a time, and acoustic stimulation was used in the non-implanted ears through the headphone. Second, speech-on-speech masking performance was measured to estimate masking release by voice gender difference between target and maskers (VGRM). The VGRM was calculated as the difference in speech recognition thresholds of target sounds in the presence of same-gender or different-gender maskers. Voice gender differences between target and masker talkers improved speech recognition performance for the bimodal CI group, but not the bilateral CI group. The bimodal CI users who benefited the most from voice gender differences were those who had the narrowest range of acoustic frequencies that fused into a single sound with stimulation from a single electrode from the CI in the opposite ear. There was no similar voice gender difference benefit of narrow binaural fusion range for the bilateral CI users. The findings suggest that broad binaural fusion reduces the acoustical information available for differentiating individual talkers in bimodal CI users, but not for bilateral CI users. In addition, for bimodal CI users with narrow binaural fusion who benefit from voice gender differences, bilateral implantation could lead to a loss of that benefit and impair their ability to selectively attend to one talker in the presence of multiple competing talkers. The results suggest that binaural pitch fusion, along with an assessment of residual hearing and other factors, could be important for assessing bimodal and bilateral CI users.

Investigating the influence of auditory streaming cues on binaural pitch fusion

Binaural pitch fusion occurs when dichotic signals eliciting a different pitch are perceived as one sound. Previously, Oh et al. (ASA 2018) investigated the effects of auditory streaming cues on binaural fusion using a modification of the ABA streaming paradigm. A dichotic stimulus (fixed tone at frequency fref in the reference ear and variable frequency in the contralateral ear) was presented at alternating intervals with a “capture” tone at fref. Binaural fusion frequency range decreased, suggesting competition of the capture with the variable frequency tone for fusion. The present study added more capture tones, allowing for a galloping percept, and varied the inter-stimulus interval (ISI), both hypothesized to decrease binaural fusion by increasing salience of the capture tone. The dichotic stimulus was presented alternating with two or three repetitions of the capture tone at fref for triplet and quadruplet paradigms, respectively. ISIs of 40 or 80ms were used. Participants reported whether they perceived galloping or two streams. Preliminary data from 5 normal-hearing listeners suggest reductions in binaural fusion range with the triplet and quadruplet paradigms, and longer ISI, compared to the original paradigm. These findings indicate that auditory grouping cues may potentially reduce binaural fusion. [Research funded by NIH/NIDCD R01DC013307.]

Revision Surgery Due to Proximal Junctional Failure and Rod Fracture in Adult Deformity Surgery at a Single Institution in Japan.

Proximal junctional failure (PJF) and rod fracture (RF) are the primary reasons for revision surgery after a long corrective fusion for the adult spinal deformity (ASD). However, many recent studies on ASD are multicenter studies from the US and European racial characteristics may differ from those of Asians. Therefore, the risk factors for revision surgery because of PJF and RF after ASD surgery were evaluated in Japanese patients. Patients with ASD who underwent corrective surgery from the thoracic vertebrae to the ilium at the authors' institution were reviewed. Demographic, surgical, and radiographic parameters were included in the analysis. Univariate and multivariate regression models were used to analyze the risk factors for PJF and RF. Two hundred and fifty-nine patients were included in the study. A total of 73 patients (28.1%) required revision surgery because of mechanical complications and 15 patients (5.7%) required revision surgery because of PJF on average 380 days after surgery. In PJF cases, body mass index (BMI) and pelvic tilt were significantly higher (p=0.01, p=0.048, respectively). BMI was an independent risk factor for revision owing to PJF (odds ratio [OR], 1.16; p=0.013). A total of 49 patients (18.9%) required revision owing to RF on average 867 days after surgery. Three-column osteotomy (p<0.001), significant blood loss (p=0.048), number of fusion segments (p=0.023), absence of lateral lumbar interbody fusion (p<0.001), and sagittal imbalance (p=0.033) were risk factors for revision surgery owing to RF in the univariate analysis. Three-column osteotomy (OR 4.41; p<0.001) and number of fusion segments (OR 1.21; p<0.009) were independent factors for revision surgery owing to RF. PJF occurred in a relatively early phase (approximately 1 year) after surgery in patients with ASD with high BMI. Conversely, RF occurred approximately 2.5 years after surgery in three-column osteotomy and spinal fusion cases that involvedlonger fusion range.

Analysis of Visual Risk Factors of Anterior Cruciate Ligament Injury of Knee Joint.

This study aimed to explore whether the defect of visual function is a risk factor of knee anterior cruciate ligament (ACL) sports injury and to provide a theoretical basis for the primary prevention of ACL sports injury. This cross-sectional study included 392 participants divided into two groups: the sports injury group (287 with sports injury of knee) and the control group (105 healthy volunteers). Participants in the sports injury group were further divided into the ACL-Intact group (133) and the ACL-Deficient group (154). Participants in the sports injury group received a questionnaire about the conditions of their injury (including injury action, site condition, weather, contact) and a visual examination by synoptophore (including binocular vision, subjective and objective oblique angle, visual fusion range, stereoacuity). Participants in the control group only received the visual examination. In the end, we found that low visual fusion range (p = 0.003) and injury action, especially quick turn (p = 0.001), sudden stop (p < 0.001) and jump (p = 0.001), are the major risk factors for ACL injury in the analysis of the integrated data. In addition, athletes with low vision fusion range have increased risk of ACL sports injury when they make a sudden stop on wooden floor, plastic floor or cement floor on cloudy days (OR = 13.208). Visual factors, especially low fusion range, significantly increase the risk of ACL sports injury.

Evaluation of Topology Optimization Using 3D Printing for Bioresorbable Fusion Cages: A Biomechanical Study in a Porcine Model.

Preclinical biomechanical study of topology optimization versus standard ring design for bioresorbable poly-ε-caprolactone (PCL) cervical spine fusion cages delivering bone morphogenetic protein-2 (BMP-2) using a porcine model. The aim was to evaluate range of motion (ROM) and bone fusion, as a function of topology optimization and BMP-2 delivery method. 3D printing technology enables fabrication of topology-optimized cages using bioresorbable materials, offering several advantages including customization, and lower stiffness. Delivery of BMP-2 using topology optimization may enhance the quality of fusion. Twenty-two 6-month-old pigs underwent anterior cervical discectomy fusion at one level using 3D printed PCL cages. Experimental groups (N=6 each) included: Group 1: ring design with surface adsorbed BMP-2, Group 2: topology-optimized rectangular design with surface adsorbed BMP-2, and Group 3: ring design with BMP-2 delivery via collagen sponge. Additional specimens, two of each design, were implanted without BMP-2, as controls. Complete cervical segments were harvested six months postoperatively. Nanocomputed tomography was performed to assess complete bony bridging. Pure moment biomechanical testing was conducted in all three planes, separately. Continuous 3D motions were recorded and analyzed. Three subjects suffered early surgical complications and were not evaluated. Overall, ROM for experimental specimens, regardless of design or BMP-2 delivery method, was comparable, with no clinically significant differences among groups. Among experimental specimens at the level of the fusion, ROM was <1.0° in flexion and extension, indicative of fusion, based on clinically applied criteria for fusion of <2 to 4°. Despite the measured biomechanical stability, using computed tomography evaluation, complete bony bridging was observed in 40% of the specimens in Group 1, 50% of Group 2, 100% of Group 3, and none of the control specimens. A topology-optimized PCL cage with BMP-2 is capable of resulting in an intervertebral fusion, similar to a conventional ring-based design of the same bioresorbable material.

Closing-opening wedge osteotomy for the treatment of congenital kyphosis in children

To evaluate the safety and effectiveness of posterior closed-open wedge osteotomy for treatment of congenital kyphosis in children. Imaging and clinical data from January 2010 to December 2019 of posterior closed-open wedge osteotomy of congenital kyphosis with at least 2-year follow up was analyzed retrospectively. Perioperative indicators such as operation time, osteotomy site, osteotomy method and occurrence of complications, and imaging indicators were observed. The 3D printed models were used to measure the expanded distance of anterior edge vertebra and closed length of spinal canal line. The clinical effect was evaluated through SRS-22 questionnaires. There were 15 CK patients in this study. The osteotomy segments and details are as follows: 1 case each for T6-9 and L2, 2 cases at T11, 3 cases at T12, and 6 cases at L1. The average operation time was 314 min, the average blood loss was 970mL, the average fusion range was 6.3 segments, and the average time of follow up was 70.5 months. The Cobb angle of local kyphosis was corrected from 65.6 ± 18.8° to 11.3 ± 7.1°(p < .001). The range of kyphosis correction was 40-90°, and average correction rate was 83.2% (67.7-95.7%). The correction was stable in follow-up, and the kyphotic angle was 11.0 ± 7.6 (p = .68). The preoperative SVA was 31.5 ± 21.8mm, and the postoperative recovery was 18.0 ± 15.5, while the last follow-up was 9.1 ± 7.9. The p values were 0.02 and 0.07 respectively. By using 3D printed models, the expanded distance of anterior edge vertebra and closed length of spinal canal line were 14.5 ± 7.5mm and 24.5 ± 8.0mm respectively. Self-image and satisfaction in SRS-22 improved significantly. There was no recurrence of deformity and junctional kyphosis. The posterior closing-opening wedge osteotom for treatment of congenital kyphosis in children is satisfactory, if selected appropriately. During the longitudinal follow-up, the patients could achieve solid fusion and the correction could be well maintained.Evidence of Confidence: IVa.

Fast non-invasive measures of binocular visual processes relevant to virtual environments

Precise coordination of many visual processes is required for clear and precise binocular viewing. However, few studies have measured these binocular processes across large samples to examine how they may differ. The two aims of the experiment were to develop new, fast and non-invasive tests for several binocular visual processes and to administer these tests to a large sample. The tests were designed to obtain thresholds of performance for vergence movement duration, latency, and range, fusion range, and static stereoacuity. Thresholds were obtained using a staircase procedure, with a two-alternative forced-choice paradigm in each staircase, which was chosen to minimise the number of trials required. The stimuli were presented stereoscopically in a mirror stereoscope, with subjective perceptions of nonius lines and static random dot stereograms as the measures of interest. The tests were administered to a sample of 108 participants and demonstrated marked variability in threshold performance within each test. These thresholds are compared to findings in previous research, and consequences for virtual reality design are explored.

Short term clinical observation of cervical anterior Hybrid surgery

To investigate the short-term clinical effect of the cervical anterior Hybrid surgery in the treatment of two-segment and three-segment cervical spondylosis. From January 2018 to January 2019, 108 patients who were performed anterior Hybrid surgery with cervical degenerative diseases were collected. The patients were divided into a two-segment group with 52 patients and a three-segment group with 56 patients according to surgical segments. In two-segment group, there were 24 males and 28 females, aged from 35 to 67 years old with an average of(45.94±14.67) years old. In three-segment group, there were 23 males and 33 females, aged from 32 to 65 years old with an average of (47.54±15.34) years old. The outcome indicators of the two groups were compared. Clinical indicators:neck disability index(NDI) was used to evaluate daily life ability, Japanese Orthopedic Association(JOA) score was used to evaluate neurological function improvement, visual analogue scale(VAS) was used to evaluate pain intensity, and general clinical results were graded according to Odom's score. Cervical range of motion (ROM), fusion and complications were measured by X-ray, CT and MRI. All operations were successfully completed and all patients were followed up for more than 12 months. The operation time of two-segment group and three-segment group were 95 to 180 min with an average of(152.30±44.74) min and 110 to 210 min with an average of (165.18±45.86) mins, the blood loss were 20 to 100 ml with an average of (32.88±8.75) ml and 20 to 150 ml with an average of(34.64±10.63) ml respectively which has no statistical differences between the two groups (P>0.05). Compared with those before surgery, NDI, JOA, VAS and Odom's scores between two groups were significantly improved at 12 months after operation(P<0.05). However, there was no significant difference in the NDI, JOA and Odom's scores between two groups (P>0.05), and VAS in three-segment group was higher than that in two-segment group. There was no significant difference in C3-C7 cervical mobility between two groups. Surgical incisions healed smoothly in all patients without complication such as spinal cord injury and cerebrospinal fluid leakage. The bone fusion of the two groups were 43 cases (82.69%) and 45 cases(80.35%) respectively. In two-segment group, there were 2 cases of adjacent segmental hyperosteogeny, and there were 3 cases of adjacent segmental hyperosteogeny and 1 case of adjacent posterior longitudinal ligament ossification in the three-segment group. In addition, in three-segment group, there was 1 case of looseness of implants with no obvious clinical symptoms. The anterior Hybrid surgery in treating multi-level cervical spondylosis could not only improve clinical symptoms of patients but also preserve mobility. Meanwhile, the efficacy and safety of Hybrid surgery in different multi-level cervical disc diseases are confirmed, proving its value in clinical practice.

Clinical features and treatment of near-work-related acquired esotropia.

To investigate the characteristics of near-work-related esotropia and the clinical efficacy of botulinum toxin type A (BTXA) injection therapy on it. A total of 107 patients aged 15-57y with near-work-related esotropia were taken as the BTXA-treated group, and 30 other peers without near-work-related esotropia were included in the control group. All participants were refractive corrected to analyse the clinical characteristics of near-work-related esotropia. All subjects were examined including Worth4 spot examination, stereoscopic vision, strabismus angle, accommodative convergence to accommodation ratio (AC/A), far and near positive and negative convergence, positive and negative fusion range, positive and negative relative accommodation. Clinical efficacy was evaluated at a period of 10mo follow-up. The distant and near stereopsis were found in 84.9% and 77.5% of patients in the BTXA-treated group, respectively. In the control group, all patients had distant and near stereopsis. The incidence of taking off one's glasses to see close objects was significantly higher in the BTXA-treated group than in the control group (P<0.05). The BTXA-treated group showed a smaller range of in-fusion (9.84±5.72)° than the control group (22.04±8.71)° (P<0.05). The near esotropia angle of the BTXA-treated group (17.08±11.98)Δ was significantly smaller than the distant esotropia angle (19.07±11.68)Δ (P<0.05). Ten months after injection, the diplopia and esotropia of most patients underwent improvements after treatment (P<0.05). This study reveals that the accommodation function and the habit of near work without wearing spectacles are associated with near-work-related esotropia, while the length of time for near work and the onset time are independent of near-work-related esotropia. Additionally, BTXA injection therapy plays a vital role in relieving diplopia and restoring eye position.

Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy.

Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy.

Posterior Surgery in the Treatment of Craniovertebral Junction Deformity with Torticollis.

ObjectiveTo investigate the clinical effect of posterior surgery in the treatment of craniovertebral junction (CVJ) deformities with torticollis and methods for preventing and treating complications in order to obtain a reasonable treatment strategy.MethodsFrom January 2007 to December 2017, 78 patients who suffered from CVJ deformities with torticollis treated by posterior surgery were analyzed. The surgical techniques were all posterior correction and fusion to restore the anatomical alignment of the craniovertebral junction. The visual analog score (VAS) and Short Form‐36 (SF‐36) health survey questionnaire were utilized to evaluate preoperative and postoperative neck pain, and changes in the torticollis angle and atlas‐dens interval (ADI) were evaluated through anteroposterior X‐ray and computed tomography. Intra‐ and postoperative complications were all recorded. One‐way ANOVA, LSD‐t test, and χ2 test were performed to evaluate the difference between the preoperative and postoperative data.ResultsThe mean follow‐up time was 37.4 ± 15.7 months, the average operation time was 115.6 ± 12.8 min, and the average blood loss was 170.8 ± 26.3 mL. According to the deformity site, the range of posterior correction and fusion was as follows: 38 cases of C1–C2, 33 cases of C0–C2, and seven cases of C0–C3. The preoperative SF‐36, VAS, torticollis angle, and ADI were 42.6 ± 8.8, 4.8 ± 1.1, 37.2 ± 11.2°, and 4.9 ± 2.3 mm, respectively. The difference was significant at 3 months post operation (p < 0.05), and there was no significant difference at the final follow‐up compared with 3 months post operation (p > 0.05).ConclusionIt can objectively achieve favorable correction and satisfactory clinical effects under posterior correction and fixation for CVJ deformities with torticollis. Intra‐ and postoperative complications can be settled by proper management.

Determining vertical fusion values from digital photographs of healthy eyes.

To determine the mean difference of vertical corneal light reflex (VCLR) among healthy eyes via digital photography. Retrospective study. The study enrolled 155, healthy eyes participants, 71 males and 84 females with a mean age of 14.7years (range 12-19years). The participants received complete eye examinations and 2 digital photographs were taken, with the flash on, while participants fixated their eyes on a near and a distant target. Two hundred and eighty qualified photographs were analyzed by Photo-Hirschberg testing using computer software. The vertical corneal light reflex ratio (VCLRR) was calculated as the distance of the corneal light reflex (CLR) to the inferior limbus or to the pupillary border divided by the horizontal corneal diameter, defined as VCLRR1 or VCLRR2. VCLRR was analyzed using Spearman's correlation. The mean ± SD of horizontal corneal diameter in near and distance photographs was 11.47 ± 0.62 and 11.37 ± 0.58mm, respectively. For correlation analysis, at 1m fixation and 6m fixation, the number of participants within an acceptable range of vertical fusion were 94.6% and 100% of participants. The 95th percentiles (estimated as the mean ± 1.64SD) in VCLRR1 between the two eyes at near and at distance fixation were 0.0316 and 0.0272, respectively; whereas the corresponding values for VCLRR2 were 0.0309 and 0.0240, respectively. The normal range of the vertical corneal light reflex ratio suggests that the Photo-Hirschberg test could be used for screening vertical strabismus cases depending on iris pigment.

Changes to Visual Parameters Following Virtual Reality Gameplay.

Introduction:Virtual reality (VR) gameplay is popular with a range of games and educational resources available. However, it puts high demands on the visual system. Current evidence shows conflicting impacts on visual parameters. Therefore, this study explores the changes to vision following VR gameplay.Methods:The study was conducted at the School of Health Sciences, University of Liverpool. All participants had binocular vision with good visual acuity and no manifest strabismus. Participants were assessed before and after playing 15 minutes of the VR game Beat Saber, which incorporated convergence and divergence movements. Clinical assessments including near point of convergence (NPC) and near point of accommodation (NPA) using the RAF rule; accommodative convergence to accommodation (AC/A) ratio; motor fusion using the prism fusion range (at 33cm), accommodation facility using +2.00/–2.00DS flipper lenses, and stereoacuity using the Frisby stereo test were assessed before and after playing.Results:Seventy-eight participants (19–25 years old) were included in the study, with 16 males and 41 females respectively. The breakpoint of convergence reduced by 0.5 cm (p = 0.001). The binocular accommodative facility improved by 2 cycles per minute (cpm); p = 0.004. The mean, near horizontal prism fusion range (PFR) base break and recovery points both worsened by of 5.0 dioptres (p = 0.003), whereas the mean near horizontal PFR base in recovery point improved by of 4.0 dioptres (p = 0.003).Discussion:The study validated previous findings as VR gameplay over-exercised and fatigued convergence muscles, but to a small degree. The VR experience improved the participants’ ability to change focus quickly and improve accommodation, as well as the divergence function of the eye. However, as the participants were retested directly after the VR gameplay, the findings were limited to short term effects on vision.

Abstract 756: Comprehensive NGS-based reference materials for variant detection in lymphoid cancer

Abstract Next Generation Sequencing (NGS) is an important technology to identify genetic changes involved in lymphoid malignancies. Genome-level understanding of these changes can aid in diagnosis, prognosis, and therapy selection. Cancer biopsies are often preserved by formalin-fixed, paraffin-embedding (FFPE) procedures which provide long-term preservation but introduce damage to nucleic acids that are present in tissue including double strand breaks, nicks, and oxidation. The gold standard for Lymphoma diagnosis is surgical removal of the lymph node making FFPE the preferred sample format for analysis. To address the need for high quality reference materials for tumor profiling assays for these patients, we developed two multiplexed, biosynthetic reference materials: the Seraseq® FFPE Lymphoma DNA Reference Material and the Seraseq® Lymphoma DNA Mutation Mix. Both contain 26 plasmids containing important SNVs, INDELs, and gene fusions in lymphoid disease. For the FFPE format, plasmids were pooled at equal concentrations and introduced into the GM24385 reference human cell line. Engineered cells were diluted to achieve desired allele frequencies (AFs) as determined by digital PCR (dPCR). The cells were processed with a proprietary FFPE protocol that mimics damage in patient samples. The QIAamp DNA FFPE Tissue Kit and the Maxwell RSC DNA FFPE Kit were used for DNA isolation. DNA was quantified by the Qubit dsDNA HS Assay and quality assessed by the Agilent TapeStation. AFs were determined by dPCR for QIAamp-extracted DNA and a custom ArcherDX VariantPlex NGS panel for DNA extracted by both kits. DNA yield was similar, 193±44 ng (QIAamp) and 124±11 ng (Maxwell); however, a higher DNA integrity number was observed with the QIAamp kit (6.1 vs 2.7). The average % AF by dPCR was 9.6±1.8 (QIAamp) (target ≥5%). The average % AF by NGS was 7.6±2.8 (QIAamp) and 3.3±1.1 (Maxwell). For the DNA mix format, the same plasmids were pooled and blended with total purified genomic DNA from GM24385 cells. The average % AF was 8.4±0.6 by dPCR (target 5-10%) and 8.2±1.6 for the ArcherDX VariantPlex NGS panel. Overall, there was good concordance between AFs measured by dPCR and NGS for the DNA and FFPE formats. We noted that overall sample performance may be impacted by the FFPE DNA extraction method used. In conclusion, these reference materials allow for monitoring of a broad range of somatic mutations and gene fusions which can aid testing laboratories in accurately detecting and quantifying various genetic events in Lymphoid patient samples. The FFPE format can serve as an extraction control in assay development, while the DNA mix format allows laboratories to go directly into NGS library preparation and dPCR. A complementary circulating tumor DNA (ctDNA) version of these reference materials would aid laboratories in detecting minimal residual disease in patient blood resulting in less invasive lymphoid testing and therapeutic response monitoring. Citation Format: Tonya N. Watkins, Benedicta Forson, Dana Ruminski Lowe, Yves Konigshofer, Catherine Huang, Omoshile Clement, Bharathi Anekella. Comprehensive NGS-based reference materials for variant detection in lymphoid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 756.