Variations in Electronic Health Record-Based Definitions of Diabetic Retinopathy Cohorts: A Literature Review and Quantitative Analysis.

Purpose: Use of the electronic health record (EHR) has motivated the need for data standardization. A gap in knowledge exists regarding variations in existing terminologies for defining diabetic retinopathy (DR) cohorts. This study aimed to review the literature and analyze variations regarding codified definitions of DR. Design: Literature review and quantitative analysis. Subjects: Published manuscripts. Methods: Four graders reviewed PubMed and Google Scholar for peer-reviewed studies. Studies were included if they used codified definitions of DR (e.g., billing codes). Data elements such as author names, publication year, purpose, data set type, and DR definitions were manually extracted. Each study was reviewed by ≥ 2 authors to validate inclusion eligibility. Quantitative analyses of the codified definitions were then performed to characterize the variation between DR cohort definitions. Main Outcome Measures: Number of studies included and numeric counts of billing codes used to define codified cohorts. Results: In total, 43 studies met the inclusion criteria. Half of the included studies used datasets based on structured EHR data (i.e., data registries, institutional EHR review), and half used claims data. All but 1 of the studies used billing codes such as the International Classification of Diseases 9th or 10th edition (ICD-9 or ICD-10), either alone or in addition to another terminology for defining disease. Of the 27 included studies that used ICD-9 and the 20 studies that used ICD-10 codes, the most common codes used pertained to the full spectrum of DR severity. Diabetic retinopathy complications (e.g., vitreous hemorrhage) were also used to define some DR cohorts. Conclusions: Substantial variations exist among codified definitions for DR cohorts within retrospective studies. Variable definitions may limit generalizability and reproducibility of retrospective studies. More work is needed to standardize disease cohorts. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Place, Race, and Lapses in Diabetic Retinopathy Care.

This cohort study investigates the association of neighborhood-level social determinants of health with lapses in diabetic retinopathy care by race and ethnicity.

Similar risk of kidney failure among patients with blinding diseases who receive ranibizumab, aflibercept, and bevacizumab: an OHDSI Network Study.

OBJECTIVE OR PURPOSE: A) To characterize the incidence of kidney failure associated with intravitreal anti-vascular endothelial growth factor (VEGF) exposure, and B) compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Subjects aged ≥18 years with ≥3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS, INTERVENTION, OR TESTING: A) The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. B) For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random-effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37,189 who received ranibizumab, 39,447 aflibercept, and 163,611 bevacizumab were included; the total treatment exposure time was 161,724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100,000 persons (range 0 to 2389), and incidence rate 743 per 100,000 person-years (0 to 2661). The meta-analysis HR of kidney failure comparing aflibercept to ranibizumab was 1.01 (95% confidence interval (CI) 0.70, 1.47, p=0.45), ranibizumab to bevacizumab 0.95 (95% CI 0.68, 1.32, p=0.62), and aflibercept to bevacizumab 0.95 (95% CI 0.65, 1.39, p=0.60). CONCLUSIONS: There was no substantially different relative risk for kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk for kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents.

Social Risk Groups in Patients With Diabetes With Differing Eye Care Utilization and Vision Outcomes.

Purpose: To evaluate whether latent class analysis on social determinants of health (SDoH) data can identify social risk groups that differ by adverse SDoH and vision outcomes in patients with diabetes. Methods: This was a prospective cohort study of adults ≥18 years with diabetes who completed a SDoH survey. Latent class analysis was used to cluster patients into social risk groups. The association of social risk group and severity of diabetic retinopathy, history of lapses in diabetic retinopathy care, and visual acuity was evaluated. Results: A total of 1006 participants were included. The three social risk groups differed by sociodemographic characteristics. The average age was 65, 60, and 54 in Groups 1, 2, and 3 respectively. Most (51%) patients in group 1 were non-Hispanic White, 66% in group 2 were non-Hispanic Black, and 80% in group 3 were Hispanic. Group 1 had the lowest burden of adverse SDoH per person (average 3.6), group 2 had 8.2, and group 3 had 10.5. In general, group 1 lacked diabetic retinopathy knowledge, group 2 had financial insecurity and difficulties with transportation, and group 3 had financial insecurity and did not have health insurance. Social risk group was associated with a history of lapses in diabetic retinopathy care, and presenting with worse vision. Conclusions and Translational Relevance: We identified distinct social risk groups among patients seeking care for diabetic retinopathy that differed by social needs, eye care utilization, and vision. Identifying these groups and their specific needs can help guide interventions to effectively address adverse SDoH and improve eye care utilization and vision outcomes among patients with diabetes.

Automated identification of fleck lesions in Stargardt disease using deep learning enhances lesion detection sensitivity and enables morphometric analysis of flecks.

PURPOSE: To classify fleck lesions and assess artificial intelligence (AI) in identifying flecks in Stargardt disease (STGD). METHODS: A retrospective study of 170 eyes from 85 consecutive patients with confirmed STGD. Fundus autofluorescence images were extracted, and flecks were manually outlined. A deep learning model was trained, and a hold-out testing subset was used to compare with manually identified flecks and for graders to assess. Flecks were clustered using K-means clustering. RESULTS: Of the 85 subjects, 45 were female, and the median age was 37 years (IQR 25-59). A subset of subjects (n=41) had clearly identifiable fleck lesions, and an AI was successfully trained to identify these lesions (average Dice score of 0.53, n=18). The AI segmentation had smaller (0.018 compared with 0.034 mm2, p<0.001) but more numerous flecks (75.5 per retina compared with 40.0, p<0.001), but the total size of flecks was not different. The AI model had higher sensitivity to detect flecks but resulted in more false positives. There were two clusters of flecks based on morphology: broadly, one cluster of small round flecks and another of large amorphous flecks. The per cent frequency of small round flecks negatively correlated with subject age (r=-0.31, p<0.005). CONCLUSIONS: AI-based detection of flecks shows greater sensitivity than human graders but with a higher false-positive rate. With further optimisation to address current shortcomings, this approach could be used to prescreen subjects for clinical research. The feasibility and utility of quantifying fleck morphology in conjunction with AI-based segmentation as a biomarker of progression require further study.

Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project.

BACKGROUND & AIMS: The coronavirus disease-2019 pandemic profoundly disrupted preventative health care services including cancer screening. As the largest provider of cirrhosis care in the United States, the Department of Veterans Affairs (VA) National Gastroenterology and Hepatology Program aimed to assess factors associated with hepatocellular carcinoma (HCC) stage at diagnosis, treatment, and survival. METHODS: Veterans with a new diagnosis of HCC in 2021 were identified from electronic health records (N = 2306). Structured medical record extraction was performed by expert reviewers in a 10% random subsample of Veterans with new HCC diagnoses. Factors associated with stage at diagnosis, receipt of treatment, and survival were assessed using multivariable models. RESULTS: Among 199 patients with confirmed HCC, the average age was 71 years and most (72%) had underlying cirrhosis. More than half (54%) were at an early stage (T1 or T2) at diagnosis. Less-advanced liver disease, number of imaging tests adequate for HCC screening, HCC diagnosis in the VA, and receipt of VA primary care were associated significantly with early stage diagnosis. HCC-directed treatments were administered to 145 (73%) patients after a median of 37 days (interquartile range, 19-54 d) from diagnosis, including 70 (35%) patients who received potentially curative treatments. Factors associated with potentially curative (vs no) treatments included HCC screening, early stage at diagnosis, and better performance status. Having fewer comorbidities and better performance status were associated significantly with noncurative (vs no) treatment. Early stage diagnosis, diagnosis in the VA system, and receipt of curative treatment were associated significantly with survival. CONCLUSIONS: These results highlight the importance of HCC screening and engagement in care for HCC diagnosis, treatment, and survival while demonstrating the feasibility of developing a national quality improvement agenda for HCC screening, diagnosis, and treatment.

Advancing Toward a Common Data Model in Ophthalmology: Gap Analysis of General Eye Examination Concepts to Standard Observational Medical Outcomes Partnership (OMOP) Concepts.

Purpose: Evaluate the degree of concept coverage of the general eye examination in one widely used electronic health record (EHR) system using the Observational Health Data Sciences and Informatics Observational Medical Outcomes Partnership (OMOP) common data model (CDM). Design: Study of data elements. Participants: Not applicable. Methods: Data elements (field names and predefined entry values) from the general eye examination in the Epic foundation system were mapped to OMOP concepts and analyzed. Each mapping was given a Health Level 7 equivalence designation-equal when the OMOP concept had the same meaning as the source EHR concept, wider when it was missing information, narrower when it was overly specific, and unmatched when there was no match. Initial mappings were reviewed by 2 graders. Intergrader agreement for equivalence designation was calculated using Cohen's kappa. Agreement on the mapped OMOP concept was calculated as a percentage of total mappable concepts. Discrepancies were discussed and a final consensus created. Quantitative analysis was performed on wider and unmatched concepts. Main Outcome Measures: Gaps in OMOP concept coverage of EHR elements and intergrader agreement of mapped OMOP concepts. Results: A total of 698 data elements (210 fields, 488 values) from the EHR were analyzed. The intergrader kappa on the equivalence designation was 0.88 (standard error 0.03, P < 0.001). There was a 96% agreement on the mapped OMOP concept. In the final consensus mapping, 25% (1% fields, 31% values) of the EHR to OMOP concept mappings were considered equal, 50% (27% fields, 60% values) wider, 4% (8% fields, 2% values) narrower, and 21% (52% fields, 8% values) unmatched. Of the wider mapped elements, 46% were missing the laterality specification, 24% had other missing attributes, and 30% had both issues. Wider and unmatched EHR elements could be found in all areas of the general eye examination. Conclusions: Most data elements in the general eye examination could not be represented precisely using the OMOP CDM. Our work suggests multiple ways to improve the incorporation of important ophthalmology concepts in OMOP, including adding laterality to existing concepts. There exists a strong need to improve the coverage of ophthalmic concepts in source vocabularies so that the OMOP CDM can better accommodate vision research. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Impact of Social Determinants of Health on Eye Care Utilization in a National Sample of People with Diabetes.

PURPOSE: To evaluate the association of social determinants of health (SDoH) with eye care utilization among people with diabetes mellitus using the 2013-2017 National Health Interview Survey (NHIS). DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Participants ≥ 18 years of age with self-reported diabetes. METHODS: The SDoH in the following domains were used: (1) economic stability; (2) neighborhood, physical environment, and social cohesion; (3) community and social context; (4) food environment; (5) education; and (6) health care system. An aggregate SDoH score was calculated and divided into quartiles, with Q4 representing those with the highest adverse SDoH burden. Survey-weighted multivariable logistic regression models evaluated the association of SDoH quartile with eye care utilization in the preceding 12 months. A linear trend test was conducted. Domain-specific mean SDoH scores were calculated, and the performance of domain-specific models was compared using area under the curve (AUC). MAIN OUTCOME MEASURE: Eye care utilization in the preceding 12 months. RESULTS: Of 20 807 adults with diabetes, 43% had not used eye care. Greater adverse SDoH burden was associated with decrements in odds of eye care utilization (P < 0.001 for trend). Participants in the highest quartile of adverse SDoH burden (Q4) had a 58% lower odds (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.37-0.47) of eye care utilization than those in Q1. The domain-specific model using economic stability had the highest performing AUC (0.63; 95% CI, 0.62-0.64). CONCLUSIONS: Among a national sample of people with diabetes, adverse SDoH were associated with decreased eye care utilization. Evaluating and intervening upon the effects of adverse SDoH may be a means by which to improve eye care utilization and prevent vision loss. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.

Importance: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely. Objective: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information. Design, Setting, and Participants: Deidentified color fundus images taken after dilation were used post hoc to train AI systems to perform regression from image to BCVA and to evaluate resultant estimation errors. Participants were patients enrolled in the VISTA randomized clinical trial through 148 weeks wherein the study eye was treated with aflibercept or laser. The data from study participants included macular images, clinical information, and BCVA scores by trained examiners following protocol refraction and VA measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Main Outcomes: Primary outcome was regression evaluated by mean absolute error (MAE); the secondary outcome included percentage of predictions within 10 letters, computed over the entire cohort as well as over subsets categorized by baseline BCVA, determined from baseline through the 148-week visit. Results: Analysis included 7185 macular color fundus images of the study and fellow eyes from 459 participants. Overall, the mean (SD) age was 62.2 (9.8) years, and 250 (54.5%) were male. The baseline BCVA score for the study eyes ranged from 73 to 24 letters (approximate Snellen equivalent 20/40 to 20/320). Using ResNet50 architecture, the MAE for the testing set (n = 641 images) was 9.66 (95% CI, 9.05-10.28); 33% of the values (95% CI, 30%-37%) were within 0 to 5 letters and 28% (95% CI, 25%-32%) within 6 to 10 letters. For BCVA of 100 letters or less but more than 80 letters (20/10 to 20/25, n = 161) and 80 letters or less but more than 55 letters (20/32 to 20/80, n = 309), the MAE was 8.84 letters (95% CI, 7.88-9.81) and 7.91 letters (95% CI, 7.28-8.53), respectively. Conclusions and Relevance: This investigation suggests AI can estimate BCVA directly from fundus photographs in patients with DME, without refraction or subjective visual acuity measurements, often within 1 to 2 lines on an ETDRS chart, supporting this AI concept if additional improvements in estimates can be achieved.

Health Disparities in Lapses in Diabetic Retinopathy Care.

Objective: To develop a novel methodology to identify lapses in diabetic retinopathy care in electronic health records (EHRs) and evaluate health disparities by race and ethnicity. Design: Retrospective cohort study. Subjects: Adult patients with diabetes mellitus who were evaluated at the Wilmer Eye Institute from January 1, 2013 to April 2, 2022. Methods: The methodology to identify lapses in care first identified diabetic retinopathy screening or treatment visits and then compared the providers' recommended follow-up timeframe with the patient's actual time to next encounter. The association of race and ethnicity with odds of lapses in care was evaluated using a mixed-effects logistic regression model controlling for age, sex, insurance, severity of diabetic retinopathy, presence of other retinal disorders, and glaucoma. Main Outcome Measures: Lapses in diabetic retinopathy care. Results: The methodology to identify diabetic retinopathy-related visits had a 95.0% (95% confidence interval, 93.0-96.6) sensitivity and 98.8% (98.1-99.3) specificity as compared with a gold standard grader. The methodology resulted in a 97.3% (96.2-98.4) sensitivity and 98.1% (97.3-98.9) specificity for detecting a follow-up recommendation, with an average error of -0.05 (-0.31 to 0.21) weeks in extracting the precise timeframe. A total of 39 561 patients with 91 104 office visits were included in the analysis. The average age was 61.4 years. More than 3 (77.6%) in 4 patients had a lapse in care. In multivariable analysis, non-Hispanic Black patients had 1.24 (1.19-1.30) odds and Hispanic patients had 1.26 (1.13-1.40) odds of ever having a lapse in care compared with non-Hispanic White patients (P < 0.001, respectively). Conclusions: We have developed a reliable methodology for identifying lapses in diabetic retinopathy care that is tailored to a provider's recommended follow-up. Using this approach, we find that 3 in 4 patients experience a lapse in diabetic retinopathy care and that these rates are higher among non-Hispanic Black and Hispanic patients. Deploying this methodology in the EHR is one potential means by which to identify and mitigate lapses in critical ophthalmic care in patients with diabetes. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

The Impact of Social Determinants of Health on Vision Loss From Cataracts and Cataract Surgery Utilization in the United States-A National Health Interview Survey Analysis.

PURPOSE: To investigate the association of social determinants of health (SDOH) factors and cataract-related outcomes disparities. DESIGN: Cross-sectional, with a nationally representative sample. METHODS: We used publicly available data from the 2008, 2016, and 2017 National Health Interview Survey data sets. Outcome measures included self-reported prevalence for ever been diagnosed with cataract, vision loss secondary to cataracts, and the likelihood of undergoing cataract surgery. Survey-weighted, multivariable logistic regression models, adjusted for age, race and ethnicity, and other relevant covariates, were used to examine the association between SDOH factors and cataract-related outcomes. RESULTS: A total of 81,551 participants were included, who were predominantly between 18 and 44 years of age (49.6%), female (51.7%), and White (74.8%). Multivariable regression models with age as a covariate showed that individuals who were not working were more likely to report having cataracts than those who were working (P < .001). Those who needed but could not afford medical care in the past year were more likely to report vision loss secondary to cataracts than their counterparts (P < .001). Uninsured participants were less likely to report undergoing cataract surgery than those with private insurance (P = .03). Individuals with higher income (poverty-income ratio: 1.00-2.99 vs <1.00) were more likely to report undergoing cataract surgery (P = .04). CONCLUSIONS: Several SDOH factors were associated with disparities in rates of cataract-related outcomes. These findings highlight the importance of ophthalmologists screening for social risks in patients with cataract, as these social factors are important barriers for access to care.

Development and validation of a mass spectrometry based analytical method to quantify the ratios in hemagglutinin trimers in quadrivalent influenza nanoparticle vaccine - FluMos-v1.

A quadrivalent influenza nanoparticle vaccine (FluMos-v1) offers long-lasting protection against multiple influenza virus strains and is composed of four strains of hemagglutinin trimer (HAT) assembled around a pentamer core. Here we report an LC-MS/MS analytical development and validation method to measure the percentage of each HAT component in FluMos-v1.

National trends in surgical subspecialisation in ophthalmology in the USA.

BACKGROUND/AIMS: To assess surgical patterns in ophthalmology by subspecialty in the USA. METHODS: Ophthalmic surgeons were categorised as comprehensive/subspecialist based on billed procedures in the 2017-2018 Medicare Provider Utilization and Payment Data. Poisson regression models assessed factors associated with physicians performing surgeries in the core domain (eg, cataract extractions) and subspecialty domain. Models were adjusted for provider gender, time since graduation, geographical region, practice setting and hospital affiliation. RESULTS: There were 10 346 ophthalmic surgeons, 74.7% comprehensive and 25.3% subspecialists. Cataract extractions were performed by 6.0%, 9.9%, 21.0%, 88.1% and 95.3% of specialists in surgical retina, neuro-ophthalmology/paediatrics, oculoplastics, glaucoma and cornea, respectively. Retina specialists were more likely to perform cataract surgery if they were 20-30 or>30 years in practice (relative risk: 2.20 (95% CI: 1.17 to 4.12) and 3.74 (95% CI: 1.80 to 7.76), respectively) or in a non-metropolitan setting (3.78 (95% CI: 1.71 to 8.38)). Among oculoplastics specialists, male surgeons (2.71 (95% CI: 1.36 to 5.42)), those in practice 10-20 years or 20-30 years (1.93 (95% CI: 1.15 to 3.26) and 1.91 (95% CI: 1.11 to 3.27), respectively) and in non-metropolitan settings (3.07 (95% CI: 1.88 to 5.02)) were more likely to perform cataract surgery. Only 26 of the 2620 subspecialists performed surgeries in two or more subspecialty domains. CONCLUSIONS: There is a trend towards surgical subspecialisation in ophthalmology in the USA whereby some surgeons focus their surgical practice on subspecialty procedures and rarely perform surgeries in the core domain.

RAD-140 Drug-Induced Liver Injury.

Background: RAD-140, one of the novel selective androgen receptor modulators (SARMs), has potent anabolic effects on bones and muscles with little androgenic effect. Despite the lack of approval for its clinical use, RAD-140 is readily accessible on the consumer market. Hepatotoxicity associated with the use of SARMs has only rarely been reported in the literature. Case Report: A 24-year-old male presented with a 2-week history of diffuse abdominal pain, scleral icterus, pruritus, and jaundice. Prior to presentation, he had been taking the health supplement RAD-140 for muscle growth for 5 weeks. He had a cholestatic pattern of liver injury, with a peak total bilirubin of 38.5 mg/dL. Liver biopsy was supportive of a diagnosis of RAD-140-associated liver injury characterized pathologically by intracytoplasmic and canalicular cholestasis with minimal portal inflammation. Symptoms and liver injury resolved after cessation of the offending agent. Conclusion: To date, only select descriptions of the potential hepatoxicity associated with the use of SARMs, including RAD-140, have been published. Given their potential hepatoxicity and ready availability on the consumer market, RAD-140 and other SARMs should be used judiciously and under close clinical supervision until further hepatic safety data become available.

Differences in receipt of recommended eye examinations by comorbidity status and healthcare utilization among nonelderly adults with diabetes.

BACKGROUND: To evaluate the effect of diabetes comorbidities by baseline healthcare utilization on receipt of recommended eye examinations. METHODS: Retrospective analysis of 310 691 nonelderly adults with type 2 diabetes in the IBM MarketScan Commercial Database from 2016 to 2019. Patients were grouped based on diabetes-concordant (related) or -discordant (unrelated) comorbidities. Logistic regression was used to estimate the prevalence ratio (PR) for eye examinations by comorbidity status, healthcare utilization, and an interaction between comorbidities and utilization, controlling for age, sex, region, and major eye disease. RESULTS: Prevalence of biennial eye examinations varied by the four comorbidity groups: 43.5% (diabetes only), 52.7% (concordant + discordant comorbidities), 48.0% (concordant comorbidities only), and 45.3% (discordant comorbidities only). In the lowest healthcare utilization tertile, the concordant-only and concordant + discordant groups had lower prevalence of examinations compared to diabetes only (PR 0.95 [95% CI 0.92-0.98] and PR 0.91 [95% CI 0.88-0.95], respectively). In the medium utilization tertile, the discordant-only and concordant + discordant groups had lower prevalence of examinations (PR 0.89 [0.83-0.95] and PR 0.94 [0.90-0.98], respectively). In the highest utilization tertile, the concordant-only and concordant + discordant groups had higher prevalence of examinations. CONCLUSIONS: Among patients with low healthcare utilization, having comorbid conditions is associated with lower prevalence of eye examinations. Among those with medium healthcare utilization, patients with diabetes-discordant comorbidities are particularly vulnerable. This study highlights populations of diabetes patients who would benefit from increased assistance in receiving vision-preserving eye examinations.

Socioeconomic disadvantage and impact on visual outcomes in patients with viral retinitis and retinal detachment.

While socioeconomic disparities impact clinical care and patient outcomes, their impact on the anatomic and visual outcomes of retinal detachment in patients with viral retinitis is unstudied. This case series included 18 eyes in 18 patients from a single academic institution between January 1, 2008 and December 31, 2018. Patient characteristics including age, sex, race, ethnicity, insurance, immunosuppression, viral retinitis, retinal detachment, retinal detachment repair, visual and anatomic outcomes, missed appointments, and Area Deprivation Index [ADI] were collected. The low-ADI group, indicating less socioeconomic disadvantage, was comprised of twelve patients with national ADIs less than 38, and the high-ADI group of six patients with national ADIs greater than 38. High-ADI patients tended to be younger (average age 38.0 versus 51.3; P = 0.06), of female sex (P = 0.03), and had more missed appointments (median 11.0 vs 0; P = 0.002). A similar number of patients in both the high-ADI and low-ADI groups underwent pars plana vitrectomy alone or pars plana vitrectomy with scleral buckle. Visual acuity was similar in the high-ADI group than in the low-ADI group at baseline, but worse at the final follow-up visit (P = 0.004). Post-operative and final visit ocular hypotony were more common in the high-ADI group (P = 0.02). In our series, socioeconomic disadvantage negatively affects the visual outcomes in patients with viral retinitis associated-retinal detachments. These factors should be considered by ophthalmologists when treating these patients.

Tyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency.

CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for the first time the significance of the tyrosine-O-sulfation proteoforms. We developed a hydrophobic interaction chromatography (HIC) method to separate and quantify different sulfation proteoforms, which led to the direct functionality assessment of tyrosine-sulfated species. The fully sulfated (4-SO3) proteoform demonstrated the highest in vitro relative antigen binding potency and neutralization efficiency against a panel of HIV-1 viruses. Interestingly, highly variable levels of 4-SO3 were produced by different clonal CHO cell lines, which helped the bNAb process development towards production of a highly potent CAP256V2LS clinical product with high 4-SO3 proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy.

Geographic variations in gender differences in cataract surgery volume among a national cohort of ophthalmologists.

PURPOSE: To assess factors associated with gender disparities in cataract surgery volume and evaluate how these differences have changed over time. SETTING: Cataract surgeons in the 2012 to 2018 Medicare database. DESIGN: Retrospective study. METHODS: The association of provider gender with the number of cataract surgeries per office visit billed was assessed with negative binomial regression models, controlling for calendar year, years in practice, hospital affiliation, geographic region, rurality, density of ophthalmologists, and the national percentile of Area Deprivation Index (ADI) score for the practice location. RESULTS: There were 8480 cataract surgeons, most of whom were male (78%). Male surgeons worked in more deprived areas with a higher ADI (median: 40 vs 33, P < .001). Female surgeons performed fewer cataracts per year (140 [95% CI, 126-154] vs 276 [95% CI, 263-288], P < .001) and billed fewer office visits (1038 [95% CI, 1008-1068] vs 1505 [95% CI, 1484-1526], P < .001). In multivariate analysis, the number of cataract surgeries per office visit was greater for males compared with females in all years in the South (average incidence rate ratio 1.80), Midwest (1.50), and West (1.53), but not in the Northeast (1.16). The relative rate of cataract surgeries between male and female surgeons in each region did not change significantly over time from 2012 to 2018 ( P > .05 in each region). CONCLUSIONS: Gender disparities in cataract volume among male and female surgeons have remained unchanged over time from 2012 to 2018. The higher cataract volume among male surgeons may be explained in part by provider practice location. Further studies are needed to better understand and address gender disparities.