Single cell transcriptomics reveals early photoreceptor states, cell-specific transcript isoforms, and cancer-predisposing features.

Human cone photoreceptors differ from rods and serve as the retinoblastoma cell-of-origin. Here, we used deep full-length single-cell RNA-sequencing to distinguish post-mitotic cone and rod developmental states and cone-specific features that contribute to retinoblastomagenesis. The analyses revealed early post-mitotic cone- and rod-directed populations characterized by higher THRB or NRL regulon activities, an immature photoreceptor precursor population with concurrent cone and rod gene and regulon expression, and distinct early and late cone and rod maturation states distinguished by maturation-associated declines in RAX regulon activity. Unexpectedly, both L/M cone and rod precursors co-expressed NRL and THRB RNAs, yet they differentially expressed functionally antagonistic NRL isoforms and prematurely terminated THRB transcripts. Early L/M cone precursors exhibited successive expression of lncRNAs along with MYCN, which composed the seventh most L/M-cone-specific regulon, and SYK, which contributed to the early cone precursors' proliferative response to RB1 loss. These findings reveal previously unrecognized photoreceptor precursor states and a role for early cone-precursor-intrinsic SYK expression in retinoblastoma initiation.

Initiation of retinopathy of prematurity screening examinations in extremely premature infants.

PURPOSE: To determine whether extremely premature infants require screening for retinopathy of prematurity (ROP) if <31 weeks' postmenstrual age (PMA). METHODS: The medical records of infants born in community hospital settings at <31 weeks' gestational age (GA) were reviewed retrospectively. Prevalence and progression of ROP in infants born at <24 weeks' GA were compared with infants born at 24-30 weeks' GA. RESULTS: A total of 2,061 records were reviewed: 1,969 infants were born at 24-30 weeks' GA; 92, at <24 weeks. Infants born <24 weeks' GA were more likely to develop pre-plus and plus disease or require treatment than infants born 24-30 weeks' GA (P < 0.0001) and did so earlier (P = 0.0001). Eight infants developed pre-plus or greater ROP <31 weeks' PMA; 6 were born <24 weeks' GA. Three infants developed plus disease or required treatment <31 weeks' PMA, the earliest at 27 and 3/7 weeks. CONCLUSIONS: Clinicians should consider initiating ROP screening examinations before 31 weeks' PMA, particularly for infants born <24 weeks' GA and those with lower birth weights.

Non-canonical Wnt pathway expression in the developing mouse and human retina.

The non-canonical Wnt pathway is an evolutionarily conserved pathway essential for tissue patterning and development across species and tissues. In mammals, this pathway plays a role in neuronal migration, dendritogenesis, axon growth, and synapse formation. However, its role in development and synaptogenesis of the human retina remains less established. In order to address this knowledge gap, we analyzed publicly available single-cell RNA sequencing (scRNAseq) datasets for mouse retina, human retina, and human retinal organoids over multiple developmental time points during outer retinal maturation. We identified ligands, receptors, and mediator genes with a putative role in retinal development, including those with novel or species-specific expression, and validated this expression using fluorescence in situ hybridization (FISH). By quantifying outer nuclear layer (ONL) versus inner nuclear layer (INL) expression, we provide evidence for the differential expression of certain non-canonical Wnt signaling components in the developing mouse and human retina during outer plexiform layer (OPL) development. Importantly, we identified distinct expression patterns of mouse and human FZD3 and WNT10A, as well as previously undescribed expression, such as for mouse Wnt2b in Chat+ starburst amacrine cells. Human retinal organoids largely recapitulated the human non-canonical Wnt pathway expression. Together, this work provides the basis for further study of non-canonical Wnt signaling in mouse and human retinal development and synaptogenesis.

Artificial Intelligence to Differentiate Pediatric Pseudopapilledema and True Papilledema on Fundus Photographs.

Purpose: To develop and test an artificial intelligence (AI) model to aid in differentiating pediatric pseudopapilledema from true papilledema on fundus photographs. Design: Multicenter retrospective study. Subjects: A total of 851 fundus photographs from 235 children (age < 18 years) with pseudopapilledema and true papilledema. Methods: Four pediatric neuro-ophthalmologists at 4 different institutions contributed fundus photographs of children with confirmed diagnoses of papilledema or pseudopapilledema. An AI model to classify fundus photographs as papilledema or pseudopapilledema was developed using a DenseNet backbone and a tribranch convolutional neural network. We performed 10-fold cross-validation and separately analyzed an external test set. The AI model's performance was compared with 2 masked human expert pediatric neuro-ophthalmologists, who performed the same classification task. Main Outcome Measures: Accuracy, sensitivity, and specificity of the AI model compared with human experts. Results: The area under receiver operating curve of the AI model was 0.77 for the cross-validation set and 0.81 for the external test set. The accuracy of the AI model was 70.0% for the cross-validation set and 73.9% for the external test set. The sensitivity of the AI model was 73.4% for the cross-validation set and 90.4% for the external test set. The AI model's accuracy was significantly higher than human experts on the cross validation set (P < 0.002), and the model's sensitivity was significantly higher on the external test set (P = 0.0002). The specificity of the AI model and human experts was similar (56.4%-67.3%). Moreover, the AI model was significantly more sensitive at detecting mild papilledema than human experts, whereas AI and humans performed similarly on photographs of moderate-to-severe papilledema. On review of the external test set, only 1 child (with nearly resolved pseudotumor cerebri) had both eyes with papilledema incorrectly classified as pseudopapilledema. Conclusions: When classifying fundus photographs of pediatric papilledema and pseudopapilledema, our AI model achieved > 90% sensitivity at detecting papilledema, superior to human experts. Due to the high sensitivity and low false negative rate, AI may be useful to triage children with suspected papilledema requiring work-up to evaluate for serious underlying neurologic conditions. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Gender Disparities in Mentorship and Career Outcomes in Ophthalmology.

Background: Gender disparities in the field of ophthalmology have been increasingly recognized. Although mentorship has been proposed as a contributing factor, there are limited data on the differences in mentorship experiences by gender among ophthalmologists. Objective: The purpose of this study was to evaluate gender disparities in mentorship experiences among ophthalmologists, and the impact of mentorship disparities on career outcomes. Design: Prospective, cross-sectional study. Setting: Web-based survey distributed through ophthalmology listservs. Participants: Ophthalmologists and ophthalmologists-in-training who completed the survey. Exposure: Training and practicing in the field of ophthalmology. Main Outcome Measures: Mentorship score based on 10 items from a previously published scale of mentorship quality and self-reported career outcomes (income, job satisfaction, achievement of career goals, and support to achieve future career goals). Results: We received survey responses from 202 male and 245 female ophthalmologists. Female ophthalmologists reported significantly lower mentorship satisfaction and worse quality of mentorship (p < 0.03). Female ophthalmologists also reported significantly lower income, worse job satisfaction, and lower rates of goal achievement and support to achieve future goals; all of these career outcomes, except income level, were partly mediated by mentorship score (mediation effect ranged from 29% to 68%, p < 0.014). Conclusions and Relevance: Gender-based inequities in achievement of career goals and job satisfaction are partly mediated by disparities in mentorship. Therefore, focused mentorship of women in ophthalmology at all career stages is imperative to reduce these inequities.

Retinoblastoma Outcomes in the Americas: A Prospective Analysis of 491 Children With Retinoblastoma From 23 American Countries.

PURPOSE: Globally, disparities exist in retinoblastoma treatment outcomes between high- and low-income countries, but independent analysis of American countries is lacking. We report outcomes of American retinoblastoma patients and explore factors associated with survival and globe salvage. DESIGN: Subanalysis of prospective cohort study data. METHODS: Multicenter analysis at 57 American treatment centers in 23 countries of varying economic levels (low income [LIC], lower-middle income [LMIC], upper-middle income [UMIC], and high income [HIC]) of 491 treatment-naïve retinoblastoma patients diagnosed in 2017 and followed through 2020. Survival and globe salvage rates analyzed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Of patients, 8 (1.6%), 58 (11.8%), 235 (47.9%), and 190 (38.7%) were from LIC, LMIC, UMIC, and HIC groups, respectively. Three-year survival rates in LICs were 60.0% (95% confidence interval [CI] 12.6-88.2) compared with 99.2% (95% CI 94.6%-99.9%) in HICs. Death was less likely in patients >4 years of age (vs ≤4 years, HR = 0.45 [95% CI 0.27-0.78], P = .048). Patients with more advanced tumors (eg, cT3 vs cT1, HR = 4.65 × 109 [95% CI 1.25 × 109-1.72 × 1010], P < .001) and females (vs males, HR = 1.98 [95% CI 1.27-3.10], P = .04) were more likely to die. Three-year globe salvage rates were 13.3% (95% CI 5.1%-25.6%) in LMICs and 46.2% (95% CI 38.8%-53.3%) in HICs. At 3 years, 70.1% of cT1 eyes (95% CI 54.5%-81.2%) vs 8.9% of cT3 eyes (95% CI 5.5%-13.3%) were salvaged. Advanced tumor stage was associated with higher enucleation risk (eg, cT3 vs cT1, subhazard ratio = 4.98 [95% CI 2.36-10.5], P < .001). CONCLUSIONS: Disparities exist in survival and globe salvage in American countries based on economic level and tumor stage demonstrating a need for childhood cancer programs.

Aqueous Humor Liquid Biopsy as a Companion Diagnostic for Retinoblastoma: Implications for Diagnosis, Prognosis, and Therapeutic Options: Five Years of Progress.

PURPOSE: To define the prospective use of the aqueous humor (AH) as a molecular diagnostic and prognostic liquid biopsy for retinoblastoma (RB). METHODS: This is a prospective, observational study wherein an AH liquid biopsy is performed at diagnosis and longitudinally through therapy for patients with RB. Tumor-derived cell-free DNA is isolated and sequenced for single nucleotide variant analysis of the RB1 gene and detection of somatic copy number alterations (SCNAs). The SCNAs are used to determine tumor fraction (TFx). Specific SCNAs, including 6p gain and focal MycN gain, along with TFx, are prospectively correlated with intraocular tumor relapse, response to therapy, and globe salvage. RESULTS: A total of 26 eyes of 21 patients were included with AH taken at diagnosis. Successful ocular salvage was achieved in 19 of 26 (73.1%) eyes. Mutational analysis of 26 AH samples identified 23 pathogenic RB1 variants and 2 focal RB1 deletions; variant allele fraction ranged from 30.5% to 100% (median 93.2%). At diagnosis, SCNAs were detectable in 17 of 26 (65.4%) AH samples. Eyes with 6p gain and/or focal MycN gain had significantly greater odds of poor therapeutic outcomes (odds ratio = 6.75, 95% CI = 1.06-42.84, P = .04). Higher AH TFx was observed in eyes with vitreal progression (TFx = 46.0% ± 40.4) than regression (22.0 ± 29.1; difference: -24.0; P = .049). CONCLUSIONS: Establishing an AH liquid biopsy for RB is aimed at addressing (1) our inability to biopsy tumor tissue and (2) the lack of molecular biomarkers for intraocular prognosis. Current management decisions for RB are made based solely on clinical features without objective molecular testing. This prognostic study shows great promise for using AH as a companion diagnostic. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Multicentre analysis of nucleic acid quantification using aqueous humour liquid biopsy in uveal melanoma: implications for clinical testing.

OBJECTIVE: Uveal melanoma (UM) tumour biopsy is limited by size and intratumour heterogeneity. We explored the potential of aqueous humour (AH) liquid biopsy for UM by quantifying analytes in samples collected at diagnosis and after brachytherapy to look for clinical correlations with tumour features. DESIGN: Case-series study. PARTICIPANTS: Sixty-six UM patients and 16 control subjects from a tertiary care hospital. METHODS: The study included 119 UM AH samples and 16 control samples analyzed for unprocessed analytes (i.e., dsDNA, miRNA, and protein) using Qubit fluorescence assays. RESULTS: Analytes were widely quantifiable among available UM AH samples (dsDNA: 94.1%; miRNA: 88.0%; protein: 95.2%) at significantly higher concentrations than among control samples (dsDNA, p = 0.008; miRNA, p < 0.0001; protein, p = 0.007). In samples taken at diagnosis, concentrations were higher at more advanced American Joint Cancer Commission stages; when comparing most advanced stage III with least advanced stage I, median dsDNA was 4 times greater (p < 0.0001), miRNA was 2 times greater (p = 0.001), and protein was 3 times greater (p < 0.0001). Analytes were quantifiable in >70% of diagnostic samples from eyes with tumours <2 mm tall. Height had a positive association with diagnostic analyte concentrations (dsDNA: R = 0.43, p = 0.0007; miRNA: R = 0.35, p = 0.01; protein: R = 0.39, p = 0.005). Samples taken after brachytherapy showed significantly higher concentrations than diagnostic samples (p < 0.01 for all). CONCLUSIONS: UM AH is a rich repository of analytes. Samples from eyes with more advanced stage and larger tumours had higher concentrations, though analytes also were quantifiable in eyes with smaller, less advanced tumours. Future analysis of AH analytes may be informative in the pursuit of personalized UM treatments.

The Nictavi Tarsus Patch: A New Device for Achieving Temporary Eyelid Closure in Lagophthalmos.

Purpose: To evaluate the effectiveness, tolerability, and safety of the Nictavi Tarsus Patch™ (NTP) in inducing temporary eyelid closure for the management of lagophthalmos in the pediatric and young adult population. Methods: We prospectively enrolled 20 patients <21 years of age who had previously been managed for lagophthalmos to trial the NTP in clinic. Inter-palpebral fissure distance (IPFD) was compared before and after the placement of the NTP in the eyes-closed position using paired t-tests. Subjects then underwent a 3-night home trial with the NTP, and parent and subject perceptions of effectiveness, comfort, and complications with the patch were analyzed using Likert scale survey questions. Results: Twenty subjects ages 2-20 years with paralytic (65%) and non-paralytic (35%) lagophthalmos were enrolled. The NTP improved lagophthalmos from a mean pre-placement IPFD of 3.3 mm to post-placement IPFD of 0.4 mm (p < 0.01). Overall, 80% of subjects achieved successful eyelid closure defined as ≤1 mm of post-placement IPFD. When stratified by subtype, 100% of subjects with paralytic lagophthalmos achieved successful eyelid closure compared to 71% of subjects with non-paralytic lagophthalmos. On a scale of 1 (worst) to 5 (best), parents rated the NTP at 4.3±0.7 for comfort while wearing, 4.3±1.0 for comfort in removing, 4.6±0.7 for ease of use, and 4.3±0.9 for effectiveness. Ninety-three percent of parents reported preferring NTP to other eyelid closure methods previously tried and indicated that they would use it again. Conclusion: The NTP is an effective, tolerable, and safe method of eyelid closure for children and young adults.

Virtual Peer Groups Reduce HbA1c and Increase Continuous Glucose Monitor Use in Adolescents and Young Adults with Type 1 Diabetes.

Background: Adolescents and young adults (AYA) from diverse and marginalized backgrounds with type 1 diabetes (T1D) generally have higher hemoglobin A1c (HbA1c) levels and less frequent continuous glucose monitor (CGM) use than AYA from more privileged backgrounds. Further, scant data address the impact of virtual peer groups (VPG) on health-related outcomes for ethnically and racially diverse AYA with T1D. Methods: CoYoT1 to California was a 15-month randomized controlled trial for AYA aged 16-25 years. In this study, AYA were randomized to receive standard care (n = 28), or CoYoT1 care (n = 40), which consisted of person-centered provider visits and bimonthly VPG. VPG were AYA-driven discussions. AYA completed the Diabetes Distress Scale (DDS), Center for Epidemiologic Studies Depression (CES-D), and Diabetes Empowerment Scale-Short Form (DES-SF) scales at baseline and all study visits. Results: Participants were 50% Latinx and 75% publicly insured. Among CoYoT1 care participants, 19 attended at least 1 VPG session (VPG attendees) and 21 did not attend any VPG sessions. VPG attendees participated in 4.1 VPG sessions on average. VPG attendees had a relative reduction in HbA1C (treatment effect -1.08%, effect sizes values [ES] = -0.49, P = 0.04) and increase in CGM use (treatment effect +47%, ES = 1.00, P = 0.02) compared to standard care. VPG participation was not associated with statistically significant changes in DDS, CES-D, and DES-SF scores. Conclusions: In a 15-month randomized controlled trial, AYA with T1D who participated in VPG reported significant improvements in HbA1c and CGM use. Peer interactions may support unmet needs of AYA with T1D from diverse and marginalized backgrounds. ClinicalTrials.gov Identifier: NCT03793673.

A Multicenter Analysis of Nucleic Acid Quantification Using Aqueous Humor Liquid Biopsy in Retinoblastoma: Implications for Clinical Testing.

Purpose: Retinoblastoma (RB) is most often diagnosed with clinical features and not diagnosed with tumor biopsy. This study describes tumor-derived analyte concentrations from aqueous humor (AH) liquid biopsy and its use in clinical assays. Design: Case series study. Participants: Sixty-two RB eyes from 55 children and 14 control eyes from 12 children from 4 medical centers. Methods: This study included 128 RB AH samples including: diagnostic (DX) samples, samples from eyes undergoing treatment (TX), samples after completing treatment (END), and during bevacizumab injection for radiation therapy after completing RB treatment (BEV). Fourteen-control AH were analyzed for unprocessed analytes (double-stranded DNA [dsDNA], single-stranded DNA [ssDNA], micro-RNA [miRNA], RNA, and protein) with Qubit fluorescence assays. Double-stranded DNA from 2 RB AH samples underwent low-pass whole-genome sequencing to detect somatic copy number alterations. Logistic regression was used to predict disease burden given analyte concentrations. Main Outcome Measures: Unprocessed analyte (dsDNA, ssDNA, miRNA, RNA and protein) concentrations. Results: Results revealed dsDNA, ssDNA, miRNA, and proteins, but not RNA, were quantifiable in most samples (up to 98%) with Qubit fluorescence assays. Median dsDNA concentration was significantly higher in DX (3.08 ng/µl) compared to TX (0.18 ng/µl; P < 0.0001) at an order of 17 times greater and 20 times greater than END samples (0.15 ng/µl; P = 0.001). Using logistic regression, nucleic acid concentrations were useful in predicting higher versus lower RB disease burden. Retinoblastoma somatic copy number alterations were identified in a TX, but not in a BEV sample, indicating the correlation with RB activity. Conclusions: Aqueous humor liquid biopsy in RB is a high-yield source of dsDNA, ssDNA, miRNA, and protein. Diagnostic samples are most useful for RB 1 gene mutational analyses. Genomic analysis may be more informative of tumor activity status than quantification alone and can be performed even with smaller analyte concentrations obtained from TX samples. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Full-field Scotopic Threshold Improvement after Voretigene Neparvovec-rzyl Treatment Correlates with Chorioretinal Atrophy.

PURPOSE: To analyze demographic and ophthalmic data in patients with and without chorioretinal atrophy after voretigene neparvovec-rzyl (VN) to identify possible causes for this phenomenon. DESIGN: Retrospective cohort study with longitudinal follow-up. PARTICIPANTS: A total of 71 eyes of 38 patients aged 2 to 44 years with RPE65-mediated retinal dystrophy treated with VN across 2 large gene therapy centers in the United States and Germany. METHODS: Patients treated with VN who developed atrophy were compared with those who did not. MAIN OUTCOME MEASURES: Gender, age, surgical center, spherical equivalent refraction, best-corrected visual acuity (BCVA), baseline full-field scotopic threshold testing (FST), and posttreatment change in FST. RESULTS: A total of 20 eyes of 12 patients developed atrophy after treatment with VN (28% of all eyes). There was no significant difference in gender, age, surgical center, or spherical equivalent refraction between the atrophy group and the no atrophy group. However, patients between school age and young adulthood were predominantly affected, whereas the youngest and the oldest patients did not develop atrophy. Baseline BCVA was better in patients who developed atrophy than those who did not (P = 0.006). The postoperative improvement in FST at 1 month was significantly higher in the atrophy group than in the no atrophy group (P = 0.0005), and this difference remained statistically significant at 1 year (P = 0.0001). There was no correlation to baseline FST, to inflammation, or to which eye was treated first. CONCLUSIONS: The degree of FST improvement after VN appears to be strongly correlated with the development of VN-related chorioretinal atrophy. This finding raises the possibility that atrophy may develop as a toxic or metabolic sequela of vector-mediated RPE65 expression. In light of the expanding number of retinal gene therapy clinical trials, this complication warrants further study because it may not be limited to VN. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Feasibility of asynchronous video-based telemedicine in the diagnosis and management of paediatric blepharoptosis.

INTRODUCTION: The purpose of this study was to assess the validity of using video glasses as part of an asynchronous telemedicine screening protocol for paediatric blepharoptosis. METHODS: A physician assistant wearing Pivothead SMART Series glasses recorded videos of paediatric patients referred for blepharoptosis in primary, down and upgaze while holding a ruler next to the eyes. An oculoplastic surgeon viewed the stored videos and recorded margin-reflex distance 1 and levator function. Using these measurements, the surgeon determined whether surgical intervention was recommended and, if so, which procedure was recommended. The surgeon recorded the same parameters for each patient based on an in-person examination performed later that day. Videos were reviewed eight months later and the same parameters were recorded. RESULTS: Twenty-nine children (n = 58 eyes) were enrolled. Margin-reflex distance 1 and levator function measurements based on same-day video review agreed with in-person examination 94.8% (intraclass correlation coefficient = 0.82) and 98.3% (intraclass correlation coefficient = 0.96) of the time, respectively. Margin-reflex distance 1 and levator function measurements based on later video review agreed with in-person examination 93.1% (intraclass correlation coefficient = 0.85) and 94.8% (intraclass correlation coefficient = 0.93) of the time, respectively. Agreement in identifying surgical candidates was almost perfect (= = 0.93) for same-day video review and substantial (= = 0.73) for later video review. Sensitivity of identifying surgical patients was 100% for both same-day video review and later video review; though specificity was lower at 94.1% for same-day video review and 76.5% for later video review. DISCUSSION: Asynchronous telemedicine encounters employing video glasses are a useful screening modality for identifying surgical paediatric blepharoptosis patients.

Evaluation of digital slit-lamp videos for paediatric anterior segment telemedicine consultations.

INTRODUCTION: This study aimed to assess the validity of telemedicine consultations using digital slit-lamp videos to detect anterior segment pathology in a paediatric population. METHODS: A paediatric anterior segment specialist simultaneously performed and recorded anterior segment examinations using the Topcon digital-ready slit lamp. Components of the examination included the eyelids/eyelashes, conjunctiva/sclera, cornea, anterior chamber, iris and lens. Masked to clinical findings, a paediatric ophthalmologist reviewed and graded the live video feed transmitted at 4 Mbps. At least three months later, both ophthalmologists graded the stored videos. We compared the sensitivity, specificity, percent agreement and weighted kappa (κ) of diagnosing anterior segment pathologies via live-streamed and store-and-forward video clips compared to the in-person standard examination. RESULTS: Examinations of 89 eyes from 45 children (5-17 years old) with known anterior segment pathology were included. Agreement between live-streamed and in-person standard examinations for conjunctiva/sclera, anterior chamber, iris and lens findings was almost perfect (sensitivity 89-96%, specificity 95-100%, κ = 0.87-0.97). Substantial agreement was found for cornea pathology (sensitivity 88%, specificity 90%, κ = 0.72), and moderate agreement was found for eyelids/eyelashes pathology (sensitivity 54%, specificity 92%, κ = 0.46). Store-and-forward results were similar, though slightly better for eyelids/eyelashes and slightly worse for conjunctiva/sclera. DISCUSSION: Digital slit-lamp videos hold promise for synchronous and asynchronous telemedicine in diagnosing paediatric anterior segment pathologies.

Greater Telehealth Use Results in Increased Visit Frequency and Lower Physician Related-Distress in Adolescents and Young Adults With Type 1 Diabetes.

BACKGROUND: Type one diabetes (T1D) management is challenging for adolescents and young adults (AYAs) due to physiological changes, psychosocial challenges, and increasing independence, resulting in increased diabetes distress and hemoglobin A1c (HbA1c). Alternative care models that engage AYAs and improve diabetes-related health outcomes are needed. METHODS: A 15-month study evaluated an adaptation of the Colorado Young Adults with T1D (CoYoT1) Care model. CoYoT1 Care includes person-centered care, virtual peer groups, and physician training delivered via telehealth. AYAs (aged 16-25 years) were partially randomized to CoYoT1 or standard care, delivered via telehealth or in-person. As the study was ending, the COVID-19 pandemic forced all AYAs to transition to primarily telehealth appointments. This secondary analysis compares changes in clinic attendance, T1D-related distress, HbA1c, and device use between those who attended more than 50% of diabetes clinic visits via telehealth and those who attended more sessions in-person throughout the course of the study. RESULTS: Out of 68 AYA participants, individuals (n = 39, 57%) who attended most (>50%) study visits by telehealth completed more diabetes care visits (3.3 visits) than those (n = 29, 43%) who primarily attended visits in-person (2.5 visits; P = .007). AYAs who primarily attended visits via telehealth maintained stable physician-related distress, while those who attended more in-person visits reported increases in physician-related distress (P = .03). CONCLUSIONS: Greater usage of telehealth improved AYA engagement with their care, resulting in increased clinic attendance and reduced physician-related diabetes distress. A person-centered care model delivered via telehealth effectively meets the needs of AYAs with T1D.

Evaluation of Streamed Hardware-to-Software Telemedicine Strabismus Consultations Utilizing Video Glasses.

Background: While video glasses have been shown to be an effective tool for real-time pediatric strabismus telemedicine consultations, the high cost of the hardware-to-hardware conferencing system and bandwidth limitations may present barriers to accessibility and widespread adoption. This study evaluates the use of video glasses with a more affordable hardware-to-software video conferencing system for real-time strabismus consultations across multiple graders. Methods: A pediatric ophthalmologist (Grader 1) wearing video glasses simultaneously performed and recorded strabismus examinations in primary gaze, with and without correction, both at distance and near. Recorded parameters included strabismus category, angle measurements, and ocular motility. Three years later, four pediatric ophthalmologists (Graders 1-4) reviewed and graded streamed video feed transmitted at 1 megabit per second (Mbps) from a hard-wired codec to software. Agreement between streamed and gold standard in-person findings was determined by weighted kappa (κ) for categorical variables, intraclass correlation coefficient (ICC) for continuous variables, and percent agreement. Results: Eighteen patients aged 4-11 years (median, 7 years) were included. Agreement in strabismus category between in-person and streamed examinations was perfect for both horizontal and vertical deviations (κ=1.0). Almost perfect agreement was found for degree manifest (tropia vs intermittent tropia vs phoria) across graders (κ=0.91, range 0.86-0.97). Agreement for angle measurements was excellent across graders (ICC = 0.97, range 0.97-0.98). Extraocular motility agreement was 90% for all graders combined, with Grader 1 having 100% agreement between her in-person and streamed examinations. Conclusion: Feed obtained from video glasses streamed through a hardware-to-software video conferencing system at 1 Mbps is a reliable tool for pediatric strabismus telemedicine evaluations.

Application of a New Alloy and Post Processing Procedures for Laser Cladding Repairs on Hypereutectoid Rail Components.

The development of a laser cladding repair strategy is critical for the continued growth of heavy-haul railway networks. Premium hypereutectoid rails have undergone laser cladding using a new martensitic stainless-steel alloy, 415SS, developed for high carbon rails after standard cladding metals were found to be incompatible. Non-destructive neutron diffraction techniques were used to measure the residual stress in different layers generated across a dissimilar metal joint during laser cladding. The internal stress distribution across the cladding, heat-affected zone (HAZ), and substrate was measured in the untempered rail, after 350 °C and 540 °C heat treatment procedures and two surface grinding operations. The martensitic 415SS depositions produce compressive stress in the cladding, regardless of tempering procedures, which may inhibit fatigue crack propagation whilst grinding operations locally relive surface stress. Balancing tensile stresses were recorded below the fusion boundary in the HAZ due to thermal gradients altering the microstructure. The combination of 540 °C tempering and 0.5 mm surface layer removal produced a desirable combination of compression in the cladding deposition with significantly reduced tensile stresses in the HAZ. A comparison with the current literature shows that this alloy achieves a unique combination of desirable hardness, low tensile stress, and compression in the cladding layer. Data obtained during strain scanning has been used to determine the location of microstructural changes at the fusion boundary and HAZ through correlation of the stress, strain, full width at half maximum (FWHM), and intensity profiles. Therefore, neutron diffraction can be used for both the accurate measurement of internal residual stress and to obtain microstructural information of a metallurgical join non-destructively.

The Economic Evaluation of Team Clinic-Group Approach to a Care Model of Early Adolescents With Type 1 Diabetes.

INTRODUCTION: Glycemic control is challenging for adolescents with type 1 diabetes (T1D). Team Clinic, a shared medical appointment model, has improved psychosocial outcomes in middle school patients with T1D. We aimed to evaluate the costs of delivering Team Clinic. METHOD: Participants were randomized into Team Clinic (n = 44) or usual care (n = 42) groups. RESULTS: We found no significant difference in 6-month total costs per subject ($3,204 [intervention] vs. $3,476 [control]. No significant differences were found in health care use, test strip use, or continuous glucose monitoring and/or pump. The intervention had more clinic visits (2.41 vs. 1.52 times) and a longer length of visit (2.34 vs. 0.74 hr, but no difference in provider time per patient per visit (median, 0.67 vs. 0.68 hr). DISCUSSION: The Team Clinic care model may help young adolescents with T1D improve psychosocial outcomes and increase completion of clinical visits without increasing costs.

Pattern and prevalence of eye disorders and diseases in school-aged children: findings from the Nationwide School Sight Sampling Survey in Armenia.

Objective: This study aims to identify the prevalence of eye disorders and their causes among secondary schoolchildren aged 6-15 years old in Armenia, based on analysis of the Nationwide School Sight Sampling Survey. Methods and Analysis: A two-stage proportionate stratified cluster sample was designed for the survey. 22 600 students were screened for visual acuity in schools; 5944 of them were selected for analysis as a nationally representative sample. Those with 20/40 or worse vision were referred to photoscreening and rapid ophthalmic assessment in schools and then were provided with vouchers for free comprehensive eye examination in eye clinics. Data were collected through data collection forms and analysed using SPSS V.23. Results: While majority of the children (85%) had normal vision, 15% had a visual acuity ≤20/40. The prevalence of vision impairment (VI) in at least one eye was 9.7% and blindness in at least one eye was 0.05%. The prevalence of abnormal vision and VI was higher among girls and older children. VI was more prevalent in urban areas. The most common diagnoses were myopia (60%), astigmatism (33.7%), hyperopia (29.5%) and strabismus (3.8%). Conclusion: Majority of the vision abnormalities and VI among schoolchildren are a result of refractive error and are treatable. Our results highlight the importance of regular eye examinations for schoolchildren to detect and prevent VI. Raising awareness among parents, school staff and children about eye health is vital.

Perspectives of patients, family members, health professionals and the public on the impact of COVID-19 on mental health.

BACKGROUND: The coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress. AIMS: This study aimed to describe the perspectives of patients with COVID-19, their family, health professionals, and the general public on the impact of COVID-19 on mental health. METHODS: A secondary thematic analysis was conducted using data from the COVID-19 COS project. We extracted data on the perceived causes and impact of COVID-19 on mental health from an international survey and seven online consensus workshops. RESULTS: We identified four themes (with subthemes in parenthesis): anxiety amidst uncertainty (always on high alert, ebb and flow of recovery); anguish of a threatened future (intense frustration of a changed normality, facing loss of livelihood, trauma of ventilation, a troubling prognosis, confronting death); bearing responsibility for transmission (fear of spreading COVID-19 in public; overwhelming guilt of infecting a loved one); and suffering in isolation (severe solitude of quarantine, sick and alone, separation exacerbating grief). CONCLUSION: We found that the unpredictability of COVID-19, the fear of long-term health consequences, burden of guilt, and suffering in isolation profoundly impacted mental health. Clinical and public health interventions are needed to manage the psychological consequences arising from this pandemic.