Expression and subcellular localization of USH1C/harmonin in human retina provides insights into pathomechanisms and therapy.

Usher syndrome (USH) is the most common form of hereditary deaf-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinae uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq analysis and immunoblotting showed abundant expression of harmonin in Müller glia cells (MGCs) and retinal neurons. Furthermore, harmonin was localized in the terminal endfeet and apical microvilli of MGCs, presynaptic region (pedicle) of cones and outer segments (OS) of rods as well as at adhesive junctions between MGCs and photoreceptor cells (PRCs) in the outer limiting membrane (OLM). Our data provide evidence for the interaction of harmonin with OLM molecules in PRCs and MGCs and rhodopsin in PRCs. Subcellular expression and colocalization of harmonin correlate with the clinical phenotype observed in USH1C patients. We also demonstrate that primary cilia defects in USH1C patient-derived fibroblasts could be reverted by the delivery of harmonin_a1 transcript isoform. Our studies thus provide novel insights into PRC cell biology, USH1C pathophysiology and development of gene therapy treatment(s).

An Orbital Manifestation of VEXAS Syndrome.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disorder characterized by systemic inflammation (vasculitis, arthritis, chondritis, dermatosis) and hematologic abnormalities (thrombosis, cytopenia, vacuolization of marrow precursors). The patient demonstrated some of the adult-onset inflammatory and hematologic features, in addition to recurrent eye pain, chemosis and orbital inflammation. This case describes an instance of VEXAS syndrome in a patient with uncommon orbital symptoms such as scleritis and myositis.

Policy and Payment Decisions on Peritoneal Dialysis in the United States: A Review.

End-stage kidney disease (ESKD) accounts for a sizable proportion of Medicare spending. Peritoneal dialysis remains an underutilized treatment modality for ESKD despite its quality of life and cost-saving benefits. Medicare policy on reimbursements and patient eligibility for dialysis coverage has been amended numerous times since its inception in 1972. Over the last two decades, Medicare policy on ESKD reimbursements has evolved from a primarily fee-for-service model to a prospective payment system, and within the past few years, it has begun including more experimental payment structures. While prior work has explored the evolution of Medicare's ESKD policy as a whole, we specifically outline the impact of Medicare policy changes on peritoneal dialysis reimbursement rates, uptake by physicians and dialysis facilities, and accessibility to patients. This narrative review offers historical insights, an overview of modern ESKD policy, actionable strategies, and policy opportunities to increase the accessibility of this treatment modality.

Impact of Demographics on Regional Visual Field Loss and Deterioration in Glaucoma.

Purpose: To elucidate the impact of demographics, including gender, race, ethnicity, and preferred language, on regional visual field (VF) loss and progression in glaucoma. Methods: Multivariable linear mixed regressions were performed to determine the impact of race, ethnicity, and preferred language on regional VF loss with adjustment for age and gender. Regional VF loss was defined by pointwise total deviation values and VF loss patterns quantified by an unsupervised machine learning method termed archetypal analysis. All cross-sectional and longitudinal analyses were performed both without and with adjustment for VF mean deviation, which represented overall VF loss severity. P values were corrected for multiple comparisons. Results: All results mentioned had corrected P values less than 0.05. Asian and Black patients showed worse pointwise VF loss than White patients with superior hemifield more affected. Patients with a preferred language other than English demonstrated worse pointwise VF loss than patients with English as their preferred language. Longitudinal analyses revealed Black patients showed worse VF loss/year compared to White patients. Patients with a preferred language other than English demonstrated worse VF loss/year compared to patients preferring English. Conclusions: Blacks and non-English speakers have more severe VF loss, with superior hemifield being more affected and faster VF worsening. Translational Relevance: This study furthered our understanding of racial, ethnic, and socioeconomic disparities in glaucoma outcomes. Understanding the VF loss burden in different racial, ethnic, and socioeconomic groups may guide more effective glaucoma screening and community outreach efforts. This research could help reduce vision loss and improve quality of life in disproportionately affected populations by guiding public health efforts to promote glaucoma awareness and access to care.

Transformer-Based Deep Learning Prediction of 10-Degree Humphrey Visual Field Tests From 24-Degree Data.

Purpose: To predict 10-2 Humphrey visual fields (VFs) from 24-2 VFs and associated non-total deviation features using deep learning. Methods: We included 5189 reliable 24-2 and 10-2 VF pairs from 2236 patients, and 28,409 reliable pairs of macular OCT scans and 24-2 VF from 19,527 eyes of 11,560 patients. We developed a transformer-based deep learning model using 52 total deviation values and nine VF test features to predict 68 10-2 total deviation values. The mean absolute error, root mean square error, and the R2 were evaluation metrics. We further evaluated whether the predicted 10-2 VFs can improve the structure-function relationship between macular thinning and paracentral VF loss in glaucoma. Results: The average mean absolute error and R2 for 68 10-2 VF test points were 3.30 ± 0.52 dB and 0.70 ± 0.11, respectively. The accuracy was lower in the inferior temporal region. The model placed greater emphasis on 24-2 VF points near the central fixation point when predicting the 10-2 VFs. The inclusion of nine VF test features improved the mean absolute error and R2 up to 0.17 ± 0.06 dB and 0.01 ± 0.01, respectively. Age was the most important 24-2 VF test parameter for 10-2 VF prediction. The predicted 10-2 VFs achieved an improved structure-function relationship between macular thinning and paracentral VF loss, with the R2 at the central 4, 12, and 16 locations of 24-2 VFs increased by 0.04, 0.05 and 0.05, respectively (P < 0.001). Conclusions: The 10-2 VFs may be predicted from 24-2 data. Translational Relevance: The predicted 10-2 VF has the potential to improve glaucoma diagnosis.

Gender and Research Productivity of Vitreoretinal Surgery Fellowship Program Directors.

BACKGROUND AND OBJECTIVE: Characteristics of vitreoretinal surgery fellowship program directors (PDs) in North America are not well described. This study reports on the gender and research productivity of vitreoretinal surgery PDs in the United States and Canada. MATERIALS AND METHODS: We reviewed demographics, total number of Scopus-indexed publications, h-index, and m-quotient for vitreoretinal surgery fellowship PDs in 2022. Descriptive statistics, student t-tests, χ2 tests, and logistic regression analyses were performed. RESULTS: Information was obtained on 83/89 (93%) PDs; 86% were male, and 84% did not have an additional graduate degree. The mean publication count was 81.54 (SD: 90.33) and mean h-index was 20.61 (SD: 16.49). There were no significant differences between female and male fellowship PDs with respect to number of publications, h-indices, and m-quotients. CONCLUSION: Women were underrepresented among vitreoretinal fellowship PDs although they had similar research productivity as their male colleagues. [Ophthalmic Surg Lasers Imaging Retina 2023;54:384-386.].

Hospitalization in maintenance peritoneal dialysis: a review.

Although hemodialysis continues to be the dominant form of dialysis in the United States, peritoneal dialysis rates continue to rise both nationally and worldwide. Peritoneal dialysis offers patients increased flexibility due to the ability to dialyze at home, leading to potential quality of life benefits for patients. However, questions exist regarding clinical outcomes in patients on peritoneal dialysis and the literature has not recently been reviewed. This review examines hospitalizations within patients utilizing peritoneal dialysis, including comparison to other dialysis modalities. Much heterogeneity exists within the literature, often explained by patient population. Recent data show all-cause, cardiovascular, and infection-related hospitalizations to be high in patients on peritoneal dialysis, although data variation limits conclusions in comparison to other modalities. This review found there is insufficient evidence to suggest admission rates are different in peritoneal dialysis than in-center hemodialysis. While the rate is similar to infectious causes, most studies report cardiovascular complications to be the leading cause of hospitalization. Some evidence suggests that cardiovascular hospitalizations occur at a higher rate in peritoneal dialysis, but further studies are required. The infection-related hospitalization rate appears to be higher in peritoneal dialysis due to rates of peritonitis, but rates of life-threatening bacteremia are lower. Differences in reporting of hospital days vs. length of stay challenge the interpretability of length of stay data between modalities, but patients on PD may spend more days per year in the hospital. In summary, hospitalization is highly prevalent in patients on peritoneal dialysis and few definitive conclusions can be drawn in comparison to other dialysis modalities. In eligible patient populations who desire increased flexibility, peritoneal dialysis is a reasonable modality choice.

Impact of COVID-19 on maintenance peritoneal dialysis patients and providers: A review.

The COVID-19 pandemic exerted complex pressures on the nephrology community. Despite multiple prior reviews on acute peritoneal dialysis during the pandemic, the effects of COVID-19 on maintenance peritoneal dialysis patients remain underexamined. This review synthesizes and reports findings from 29 total cases of chronic peritoneal dialysis patients with COVID-19, encompassing 3 case reports, 13 case series, and 13 cohort studies. When available, data for patients with COVID-19 on maintenance hemodialysis are also discussed. Finally, we present a chronological timeline of evidence regarding the presence of SARS-CoV-2 in spent peritoneal dialysate and explore trends in telehealth as they relate to peritoneal dialysis patients during the pandemic. We conclude that the COVID-19 pandemic has underscored the efficacy, flexibility, and utility of peritoneal dialysis.

Artifact Correction in Retinal Nerve Fiber Layer Thickness Maps Using Deep Learning and Its Clinical Utility in Glaucoma.

Purpose: Correcting retinal nerve fiber layer thickness (RNFLT) artifacts in glaucoma with deep learning and evaluate its clinical usefulness. Methods: We included 24,257 patients with optical coherence tomography and reliable visual field (VF) measurements within 30 days and 3,233 patients with reliable VF series of at least five measurements over ≥4 years. The artifacts are defined as RNFLT less than the known floor value of 50 µm. We selected 27,319 high-quality RNFLT maps with an artifact ratio (AR) of <2% as the ground truth. We created pseudo-artifacts from 21,722 low-quality RNFLT maps with AR of >5% and superimposed them on high-quality RNFLT maps to predict the artifact-free ground truth. We evaluated the impact of artifact correction on the structure-function relationship and progression forecasting. Results: The mean absolute error and Pearson correlation of the artifact correction were 9.89 µm and 0.90 (P < 0.001), respectively. Artifact correction improved R2 for VF prediction in RNFLT maps with AR of >10% and AR of >20% up to 0.03 and 0.04 (P < 0.001), respectively. Artifact correction improved (P < 0.05) the AUC for progression prediction in RNFLT maps with AR of ≤10%, >10%, and >20%: (1) total deviation pointwise progression: 0.68 to 0.69, 0.62 to 0.63, and 0.62 to 0.64; and (2) mean deviation fast progression: 0.67 to 0.68, 0.54 to 0.60, and 0.45 to 0.56. Conclusions: Artifact correction for RNFLTs improves VF and progression prediction in glaucoma. Translational Relevance: Our model improves clinical usability of RNFLT maps with artifacts.

Artifact-Tolerant Clustering-Guided Contrastive Embedding Learning for Ophthalmic Images in Glaucoma.

Ophthalmic images, along with their derivatives like retinal nerve fiber layer (RNFL) thickness maps, play a crucial role in detecting and monitoring eye diseases such as glaucoma. For computer-aided diagnosis of eye diseases, the key technique is to automatically extract meaningful features from ophthalmic images that can reveal the biomarkers (e.g., RNFL thinning patterns) associated with functional vision loss. However, representation learning from ophthalmic images that links structural retinal damage with human vision loss is non-trivial mostly due to large anatomical variations between patients. This challenge is further amplified by the presence of image artifacts, commonly resulting from image acquisition and automated segmentation issues. In this paper, we present an artifact-tolerant unsupervised learning framework called EyeLearn for learning ophthalmic image representations in glaucoma cases. EyeLearn includes an artifact correction module to learn representations that optimally predict artifact-free images. In addition, EyeLearn adopts a clustering-guided contrastive learning strategy to explicitly capture the affinities within and between images. During training, images are dynamically organized into clusters to form contrastive samples, which encourage learning similar or dissimilar representations for images in the same or different clusters, respectively. To evaluate EyeLearn, we use the learned representations for visual field prediction and glaucoma detection with a real-world dataset of glaucoma patient ophthalmic images. Extensive experiments and comparisons with state-of-the-art methods confirm the effectiveness of EyeLearn in learning optimal feature representations from ophthalmic images.

Best practices for interviewing applicants for medical school admissions: a systematic review.

INTRODUCTION: Interviews are commonly used to select applicants for medical school, residency, and fellowship. However, interview techniques vary in acceptability, feasibility, reliability, and validity. This systematic review investigated the effectiveness of different interview methods in selecting the best qualified applicants for admission to medical school and developed a logic model to implement best practices for interviewing. METHODS: Five electronic literature databases were searched for comparative studies related to interviewing in medical schools from inception through February 1, 2021. Inclusion criteria included publications in English that compared different methods of conducting a selection interview in medical schools with a controlled trial design. General study characteristics, measurement methodologies, and outcomes were reviewed. Quality appraisal was performed using the Medical Education Research Study Quality Instrument (MERSQI) and the Oxford Risk of Bias Scale. Based on these findings, a logic model was constructed using content analysis. RESULTS: Thirteen studies were included. The multiple mini-interview (MMI) was reliable, unbiased, and predicted clinical and academic performance; the virtual MMI increased reliability and lowered costs. For unstructured interviews, blinding interviewers to academic scores reduced bias towards higher scorers; student and faculty interviewers rated applicants similarly. Applicants preferred structured over unstructured interviews. Study quality was above average per the MERSQI, risk of bias was high per the Oxford scale, and between-study heterogeneity was substantial. DISCUSSION: There were few high-quality studies on interviewing applicants for admission to medical school; the MMI appears to offer a reliable method of interviewing. A logic model can provide a conceptual framework for conducting evidence-based admissions interviews.

Predictors of future research productivity among ophthalmology residents.

PURPOSE: To investigate the characteristics of first-year ophthalmology residents associated with high research productivity in twelve years. METHODS: All first-year ophthalmology residents in the United States (US) in 2009 listed by institutional websites were identified. Publications were obtained from Scopus and Google Scholar, h-indices were calculated, and medical school characteristics such as research productivity, region, rank, and average USMLE Steps 1 and 2 scores were obtained from National Institutes of Health, US Census Bureau, and US News. RESULTS: Data were obtained on 70% (316/453) of residents; most were male, had Doctor of Medicine (MD) degrees, and graduated from medical schools in the US or Canada. Having an additional graduate degree [OR: 3.05, 95% CI: 1.07-8.67], between 1 and 3 publications [OR: 4.16, 95% CI: 2.22-7.79], or 4 or more publications [OR: 14.27, 95% CI: 3.13-64.94] were associated with higher future research productivity. CONCLUSION: Graduate degrees and publication count were key predictors of future research productivity among ophthalmology residents in the US.

Characteristics of First-Year Residents in Top-Ranked United States Ophthalmology Residency Programs.

Objective The aim of the study is to investigate the characteristics of first-year residents associated with attending a top-ranked United States (U.S.) ophthalmology residency program over the past decade. Methods First-year ophthalmology residents in 2009, 2013, 2016, and 2019 were identified from institutional websites, Doximity, LinkedIn and the Wayback Machine. Publications were obtained from Scopus and Google Scholar; research productivity was measured using the h -index, and medical school region based on U.S. Census Bureau designations. Medical school and ophthalmology training program rankings were based on U.S. News & World Report (U.S. News) rankings and National Institutes of Health (NIH) funding. One-way ANOVA, Wilcoxon rank sum, χ 2 , and t -tests were used to analyze trends, and odds ratios (ORs) were calculated using logistic regression. Results Data were obtained on 81% (1,496/1,850) of the residents; 43% were female; 5% were international medical graduates (IMGs); and 10% had other graduate degrees. Over the decade, the mean h -index increased (0.87-1.26; p <0.05) and the proportion of residents who attended a top 20 medical school decreased (28-18%; p <0.05). In a multivariate logistic regression model, characteristics associated with being a first-year resident in a top 20 program ranked by U.S. News were female gender [OR: 1.32, 95% CI: 1.02-1.72], having a Master's degree [OR: 2.28, 95% CI: 1.29-4.01] or PhD [OR: 2.23, 95% CI: 1.32-3.79], attending a top 20 [OR: 5.26, 95% CI: 3.66-7.55] or a top 40 medical school by NIH funding [OR: 2.45, 95% CI: 1.70-3.54], attending a medical school with a mean USMLE Step 2 score above 243 [OR: 1.64, 95% CI: 1.01-2.67] or located in the Northeast [OR: 2.00, 95% CI: 1.38-2.89] and having an h -index of one or more [OR: 1.92, 95% CI: 1.47-2.51]. Except for gender, these characteristics were also significantly associated with matching to a top 20 ophthalmology program by NIH funding. Conclusion Female gender, graduate degrees, research productivity, and attending a medical school with high research productivity, high mean USMLE Step 2 score or in the Northeast were key characteristics of first-year residents in top-ranked U.S. ophthalmology residency programs.

Global Inequalities in Youth Mortality, 2007-2012.

OBJECTIVES: There is limited cross-national research on youth mortality. We examined age-and gender-variations in all-cause mortality among youth aged 15-34 years across 52 countries. METHODS: Using the 2014 WHO mortality database, mortality rates for all countries were computed for the latest available year between 2007 and 2012. Rates, rate ratios, and ordinary least squares (OLS) and Poisson regression were used to analyze international variation in mortality. RESULTS: Mortality rates among youth aged 15-34 years varied from a low of 28.4 deaths per 100,000 population for Hong Kong to a high of 250.6 for Russia and 619.1 for South Africa. For men aged 15-34, Singapore and Hong Kong had the lowest mortality rates (≈40 per 100,000), compared with South Africa and Russia with rates of 589.7 and 383.3, respectively. Global patterns in mortality among women were similar. Youth aged 15-24 in South Africa had 14 times higher mortality and those in the Philippines, Mexico, Russia, Colombia, and Brazil had 5-7 times higher mortality than those in Hong Kong. Youth aged 25-34 in Russia and South Africa had, respectively, 10 and 29 times higher mortality than their counterparts in Hong Kong. United States (US) had the 12th highest mortality rate among youth aged 15-24 and the 13th highest rate among youth aged 25-34. Overall, the US youth had 2-3 times higher rates of mortality than their counterparts in many industrialized countries including Hong Kong, Singapore, Netherlands, Switzerland, Germany, Norway, and Sweden. Income inequality, unemployment rate, and human development explained 50-66% of the global variance in youth mortality. Compared to the countries with low unemployment and income inequality and high human development levels, countries with high unemployment and income inequality and low human development had, respectively, 343%, 213%, and 205% higher risks of youth mortality. CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: Marked international disparities in youth all-cause mortality largely reflect differences in violence and injury deaths and in such risk factors as unemployment, income inequality, human development, and alcohol consumption. The US ranks in the upper quartile of all-cause mortality, with youth in Canada and many western industrialized countries showing signifi cantly lower mortality risks than the US youth.