Corneal Opacity in the United States: An American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) Study.

PURPOSE: Vision loss associated with opacification of the cornea is one of the leading causes of blindness globally. However, the epidemiological data pertaining to the demographics, associated etiological causes and reduced vision in corneal opacity patients continue to be sparse. This study assesses the case frequencies, underlying etiologies, and vision outcomes in patients diagnosed with corneal opacity, in the United States. DESIGN: Retrospective cohort study PARTICIPANTS: Patients in the IRIS® Registry (Intelligent Research in Sight) who were diagnosed with corneal opacity between January 1st, 2013, and November 30th, 2020. METHODS: The IRIS Registry contains demographic and clinical data of 79,887,324 patients who presented to eye clinics during the study period. We identified patients with corneal opacity using International Classification of Disease (ICD) codes (ICD-9, and -10) of "371" (corneal scar) and "H17" (corneal opacity), respectively. The analyzed data included demographic parameters included age, sex, race, ethnicity, and geographical location. We evaluated clinical data including laterality, etiology, disease descriptors, and best-corrected visual acuity (VA) up to 1 year before the onset (± 30 days), at the time of diagnosis, and at one year following diagnosis (± 30 days). MAIN OUTCOME MEASURES: Case frequencies, etiology, and vision outcomes in patients diagnosed with corneal opacity. RESULTS: We identified 5,220,382 patients who were diagnosed with corneal opacity and scars using H17 (ICD-10) and 371.0 (ICD-9) codes over seven years. The case frequency of corneal opacity during the study period was 6,535 cases per 100,000 patients (6.5%). The mean age of the patients was 63.36±18.14 years and the majority were female (57.6%). In the cohort, 38.39% and 30.00% of patients had bilateral and unilateral corneal opacity, respectively. Most of the patients were White (69.13%), followed by Black or African American (6.84%), Asian (2.45%), American Indian or Alaska Native(0.34%), Native Hawaii or other Pacific Islander(0.19%). Among the patients with corneal opacity, 7.34% had Hispanic or Latino ethnicity. The primary etiologies associated with corneal opacity included corneal dystrophies (64.66%) followed by edema (18.25%), ulcer (7.78%), keratoconjunctivitis (7.18%), degeneration (5.62%), neovascularization (6.27%), and trauma (5.28%). Visual acuity of the patients significantly worsened due to corneal opacity (0.46±0.74 logMAR; ∼20/58 in Snellen) and did not improve to the baseline (0.37±0.68 logMAR, ∼20/46 in Snellen) post-management (0.43±0.77 logMAR, ∼20/54 in Snellen). The multiple linear regression analysis showed worse vision outcomes in females (compared to males), and Asian, Black or African American, and American Indian or Alaska Native (compared to White) patients. Additionally, worse vision outcomes were observed in patients with opacity associated with corneal malformation, degenerative disorders, edema, injury, and ulcer compared to those with hereditary corneal dystrophy. CONCLUSIONS: Our study shows that the corneal opacity was diagnosed in 6.5% of the patients in the IRIS Registry and it was primarily associated with corneal dystrophies. The final vision outcomes in corneal opacity patients were significantly worse compared to baseline. The worse vision outcomes were associated with sociodemographic differences that might be associated with disparities in access, utilization, and care patterns.

Factors Associated with Missing Sociodemographic Data in the IRIS® (Intelligent Research in Sight) Registry.

Purpose: To describe the prevalence of missing sociodemographic data in the IRIS® (Intelligent Research in Sight) Registry and to identify practice-level characteristics associated with missing sociodemographic data. Design: Cross-sectional study. Participants: All patients with clinical encounters at practices participating in the IRIS Registry prior to December 31, 2020. Methods: We describe geographic and temporal trends in the prevalence of missing data for each sociodemographic variable (age, sex, race, ethnicity, geographic location, insurance type, and smoking status). Each practice contributing data to the registry was categorized based on the number of patients, number of physicians, geographic location, patient visit frequency, and patient population demographics. Main Outcome Measures: Multivariable linear regression was used to describe the association of practice-level characteristics with missing patient-level sociodemographic data. Results: This study included the electronic health records of 66 477 365 patients receiving care at 3306 practices participating in the IRIS Registry. The median number of patients per practice was 11 415 (interquartile range: 5849-24 148) and the median number of physicians per practice was 3 (interquartile range: 1-7). The prevalence of missing patient sociodemographic data were 0.1% for birth year, 0.4% for sex, 24.8% for race, 30.2% for ethnicity, 2.3% for 3-digit zip code, 14.8% for state, 5.5% for smoking status, and 17.0% for insurance type. The prevalence of missing data increased over time and varied at the state-level. Missing race data were associated with practices that had fewer visits per patient (P < 0.001), cared for a larger nonprivately insured patient population (P = 0.001), and were located in urban areas (P < 0.001). Frequent patient visits were associated with a lower prevalence of missing race (P < 0.001), ethnicity (P < 0.001), and insurance (P < 0.001), but a higher prevalence of missing smoking status (P < 0.001). Conclusions: There are geographic and temporal trends in missing race, ethnicity, and insurance type data in the IRIS Registry. Several practice-level characteristics, including practice size, geographic location, and patient population, are associated with missing sociodemographic data. While the prevalence and patterns of missing data may change in future versions of the IRIS registry, there will remain a need to develop standardized approaches for minimizing potential sources of bias and ensure reproducibility across research studies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Epidemiology of Orbital Inflammatory Disease: An AAO IRIS Registry Study.

PURPOSE: The current study queries the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) registry for data on the epidemiology, work-up, and management patterns of autoimmune orbital inflammation. METHODS: Analysis and description of patient data from the IRIS registry between 2013 and 2019 reviewing patients with autoimmune or idiopathic orbital inflammation with filters based on International Classification of Disease (ICD) and Current Procedural Terminology (CPT) codes. Patients with thyroid eye disease, orbital cellulitis, and orbital abscess were excluded. MAIN OUTCOME MEASURES: Demographic descriptions included gender, age, geographic region, and treatment. Sub-analysis was performed by assessing rates of imaging, biopsy, lab work-up, and diagnostic categories. RESULTS: In a final cohort of 20,584 patients, the mean age of onset of orbital inflammation was 51.7 years; 67% female; and 63% Caucasian, 21% unknown, 12% Black, 2.6% Asian, and 1.5% other. Only 49 had imaging, 78 had laboratory work-up, and 1,411 had biopsy codes. Treatment results showed 166 patients receiving antibiotics, 224 patients receiving steroids, and 35 patients receiving both. CONCLUSIONS: This study assessed the epidemiology, diagnostic patterns, and treatment patterns for orbital inflammation through the AAO IRIS registry. Practise patterns suggest a relatively low overall rate of imaging and laboratory studies compared to biopsies, although this certainly under-represents the actual number of imaging and laboratory studies and exemplifies the inherent imprecision of using a large database. However, the methodology of this study provides a framework of approaching the IRIS registry for oculoplastic research.

The Epidemiology and Risk Factors for the Progression of Sympathetic Ophthalmia in the United States: An IRIS Registry Analysis.

PURPOSE: To investigate the demographic and clinical characteristics of patients with sympathetic ophthalmia (SO) and define the risk factors for its incidence following trauma and ophthalmic procedures. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the American Academy of Ophthalmology's (Academy) IRIS Registry (Intelligent Research in Sight) who were (n=1523) or were not diagnosed with SO following a documented procedure or trauma between January 1, 2013, and December 31, 2019. METHODS: Multiple demographic and clinical factors were collected, descriptive statistics and prevalence were calculated, and multivariate linear regression models were fit to the data. MAIN OUTCOME MEASURES: Prevalence of SO, demographic and clinical characteristics, and beta coefficient (ß) estimates of demographic and clinical characteristics impacting time to SO onset after procedure (Procedure Only cohort) or trauma (Trauma cohort). RESULTS: Of 65,348,409 distinct IRIS Registry patients, 1523 (0.0023%) were diagnosed with SO between 2013 and 2019, and also had a documented preceding trauma or procedure. Of these, 927 (60.87%) were female, 1336 (87.72%) belonged to the Procedure Only cohort, and 187 (12.28%) belonged to the Trauma cohort. The prevalence of SO after trauma was 0.0207%, whereas after procedures it was 0.0124%. The highest risk of procedure-related SO was seen in patients with history of "other anterior segment" (0.122%) followed by glaucoma (0.066%) procedures, whereas the lowest prevalence was noted with cataract surgeries (0.011%). The average time to onset of SO across both cohorts combined was 527.44 (±715.60) days, with statistically significant differences between the 2 cohorts (P < .001). On average, the time to onset from inciting event to SO was shorter with increasing age, by 9.02 (95% CI: -11.96, -6.08) days for every 1-year increase. CONCLUSIONS: SO following trauma and ophthalmic procedure is potentially rarer than previously reported, as measured in this large ophthalmic medical record database. Female sex may be a risk factor for SO. Older age may be a risk factor for quicker onset. These findings can guide clinical decision-making and management.

The epidemiology of pediatric dry eye disease in the United States: An IRIS® registry (Intelligent Research in Sight) analysis.

PURPOSE: Dry-eye disease (DED) is a chronic progressive ocular surface disorder with limited studies in the pediatric population. The Academy of Ophthalmology's IRIS® Registry was leveraged to investigate the prevalence of DED in the pediatric population (PDED, patients <18 years old) and the demographic differences of DED between pediatric and adult patients (ADED). METHODS: Retrospective cohort study. Patients with DED between January 1st, 2013 and December 31st, 2019 (N = 4,795,979) were included. Descriptive statistics, Pearson's chi-squared tests and two-sample proportions tests were conducted to compare key demographic distributions between the ADED and PDED cohorts. RESULTS: The average age at onset for ADED patients was 61.06 (±14.75) years and for PDED patients was 12.51 (±3.86). The overall tests for independence and the individual tests of proportions of each category were statistically significant for all demographic characteristics (p < 0.001). Characteristics with the largest discrepancies between patients of PDED and the IRIS Registry pediatric patient pool (PIRIS) included female sex (58.08 % vs. 50.60 %), male sex (41.58 % vs. 48.78 %) and Asian race (6.02 % vs. 3.11 %) respectively. Within the PDED cohort, females were at higher risk of PDED (58 % vs. 42 %). PDED was more prevalent in children with refractive errors (76 %) and eyelid/conjunctival disorders (41 %). Characteristics with the largest discrepancies between PDED and ADED patients included female sex (58.08 % vs. 68.12 %), male sex (41.58 % vs. 31.55 %) and Caucasian race (50.24 % vs. 67.06 %) respectively. CONCLUSIONS: Significant differences in the PDED cohort are demonstrated in this study. PDED was more prevalent in the female sex and Caucasian race compared to PIRIS and was more commonly associated with refractive errors and eyelid/conjunctival disorders.

Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS® Registry Analysis.

BACKGROUND AND OBJECTIVE: This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS® Registry. PATIENTS AND METHODS: This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed. RESULTS: The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion. CONCLUSIONS: In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:220-226.].

Intravitreal Antibiotics versus Early Vitrectomy plus Intravitreal Antibiotics for Post-Injection Endophthalmitis: an IRIS® Registry (Intelligent Research in Sight).

PURPOSE: To determine if intravitreal injection of antibiotics alone versus early pars plana vitrectomy (PPV) plus injection of intravitreal antibiotics predicted better or worse visual outcomes for patients with endophthalmitis after anti-vascular endothelial growth factor (anti-VEGF) injections. DESIGN: Retrospective cohort study PARTICIPANTS: Patients developing endophthalmitis after receiving an intravitreal anti-VEGF injection from the American Academy of Ophthalmology IRIS® Registry between 2016 and 2020. METHODS: Inclusion criteria were endophthalmitis diagnosis within 1 to 28 days after anti-VEGF injection and a recorded visual acuity (VA) at baseline, on the day of diagnosis, and post-treatment. Patients in the Injection Only group underwent intravitreal injection of antibiotics alone and in the Early Vitrectomy group received PPV with intravitreal antibiotics or intravitreal injection followed by PPV within 2 days of diagnosis. Patients were excluded if they had cataract surgery during the study, intravitreal steroids before endophthalmitis, or intermediate/posterior uveitis or cystoid macular edema. The study created a 1:1 matched cohort using Mahalanobis Distance Matching, accounting for the differences in VA at baseline and diagnosis. MAIN OUTCOME MEASURES: Post-treatment logMAR VA RESULTS: 1,044 patients diagnosed with post-injection endophthalmitis met the inclusion and exclusion criteria. In the unmatched cohort, there were 935 patients in the Injection Only and 109 in the Early Vitrectomy group. In 1:1 matched cohort 218 patients (109 in each group) were included; the median logMAR VAs were 0.32 [20/40-20/50] at baseline, 0.88 [∼20/150] at diagnosis, and 0.57 [20/70-20/80] post-treatment. There were no statistically significant differences in the visual outcomes between the two matched treatment groups (b = 0.05, p = 0.23); including the subgroup of patients with VA worse than 1.0 logMAR (b = 0.05, p = 0.452). CONCLUSIONS: There was no significant difference in final VA outcomes between patients receiving Injection Only and those treated with Early Vitrectomy for post-injection endophthalmitis. The findings support the use of either treatment strategy.

COVID-19 Testing Practices, Preventive Behaviors, and Factors Associated With Test Positivity: Population-Based Statewide Survey Study.

BACKGROUND: The COVID-19 pandemic has challenged public health efforts globally. Timely population-based surveillance is crucial to support public health programs and policies to limit the spread of COVID-19. The South Carolina (SC) Sampling and Testing Representative Outreach for Novel Coronavirus Guidance (SC STRONG) statewide initiative was established to estimate population-level prevalence and immunity and characterize the transmission dynamics of SARS-CoV-2 using community testing and online surveys. OBJECTIVE: This paper aimed to leverage the survey data collected as part of the initiative to understand risk perceptions, testing practices, and preventive behaviors and identify risk factors for COVID-19 test positivity in SC over time. METHODS: Probability proportionate to size cluster random sampling was used to select SC residents to participate in testing for COVID-19 infection and antibodies and to complete an online survey. This paper focuses on data from the online surveys completed between November 2020 and June 2021. Descriptive statistics were used to describe risk perceptions, attitudes and behaviors, and associated changes over time. Univariate and multivariate logistic regression models were used to identify factors associated with self-reported COVID-19 test positivity. RESULTS: Among the 7170 online survey respondents, 58.7% (4213/7170) self-reported ever testing for COVID-19. The most commonly cited barriers to testing were inconvenient dates, time, and location, as well as discomfort. Overall, 18.7% (790/7170) of respondents reported a history of COVID-19 test positivity. Multivariate logistic regression results indicated that individuals who were aged 50 years or older, self-identified as Black/African American, were obese, and were employed as frontline health care workers or nursing home staff were more likely to self-report COVID-19 test positivity. By contrast, there was a decreased likelihood of test positivity among respondents who were concerned about the burden of COVID-19 in their community and about being infected. CONCLUSIONS: Strategies to remove testing barriers should be implemented to improve access. Our findings provide insights on statewide testing patterns, adoption of prevention behaviors, and risk factors for infection and may inform public health strategies to curb transmission.

Plakoglobin is a mechanoresponsive regulator of naive pluripotency.

Biomechanical cues are instrumental in guiding embryonic development and cell differentiation. Understanding how these physical stimuli translate into transcriptional programs will provide insight into mechanisms underlying mammalian pre-implantation development. Here, we explore this type of regulation by exerting microenvironmental control over mouse embryonic stem cells. Microfluidic encapsulation of mouse embryonic stem cells in agarose microgels stabilizes the naive pluripotency network and specifically induces expression of Plakoglobin (Jup), a vertebrate homolog of ß-catenin. Overexpression of Plakoglobin is sufficient to fully re-establish the naive pluripotency gene regulatory network under metastable pluripotency conditions, as confirmed by single-cell transcriptome profiling. Finally, we find that, in the epiblast, Plakoglobin was exclusively expressed at the blastocyst stage in human and mouse embryos - further strengthening the link between Plakoglobin and naive pluripotency in vivo. Our work reveals Plakoglobin as a mechanosensitive regulator of naive pluripotency and provides a paradigm to interrogate the effects of volumetric confinement on cell-fate transitions.

Determinants of COVID-19 Vaccinations among a State-Wide Year-Long Surveillance Initiative in a Conservative Southern State.

By the end of 2021, the COVID-19 pandemic resulted in over 54 million cases and more than 800,000 deaths in the United States, and over 350 million cases and more than 5 million deaths worldwide. The uniqueness and gravity of this pandemic have been reflected in the public health guidelines poorly received by a growing subset of the United States population. These poorly received guidelines, including vaccine receipt, are a highly complex psychosocial issue, and have impacted the successful prevention of disease spread. Given the intricate nature of this important barrier, any single statistical analysis methodologically fails to address all convolutions. Therefore, this study utilized different analytical approaches to understand vaccine motivations and population-level trends. With 12,975 surveys from a state-wide year-long surveillance initiative, we performed three robust statistical analyses to evaluate COVID-19 vaccine hesitancy: principal component analysis, survival analysis and spatial time series analysis. The analytic goal was to utilize complementary mathematical approaches to identify overlapping themes of vaccine hesitancy and vaccine trust in a highly conservative US state. The results indicate that vaccine receipt is influenced by the source of information and the population's trust in the science and approval process behind the vaccines. This multifaceted statistical approach allowed for methodologically rigorous results that public health professionals and policy makers can directly use to improve vaccine interventions.

Origin and function of the yolk sac in primate embryogenesis.

Human embryogenesis is hallmarked by two phases of yolk sac development. The primate hypoblast gives rise to a transient primary yolk sac, which is rapidly superseded by a secondary yolk sac during gastrulation. Moreover, primate embryos form extraembryonic mesoderm prior to gastrulation, in contrast to mouse. The function of the primary yolk sac and the origin of extraembryonic mesoderm remain unclear. Here, we hypothesise that the hypoblast-derived primary yolk sac serves as a source for early extraembryonic mesoderm, which is supplemented with mesoderm from the gastrulating embryo. We discuss the intricate relationship between the yolk sac and the primate embryo and highlight the pivotal role of the yolk sac as a multifunctional hub for haematopoiesis, germ cell development and nutritional supply.