A neuropsychiatric case of delayed post-hypoxic leukoencephalopathy from opioid intoxication resulting in Anton-Babinski syndrome and quadriplegia.

This is the case of a 26-year-old male who developed Anton Babinski syndrome (ABS), quadriplegia, and delayed post-hypoxic leukoencephalopathy (DPHL) after an opioid overdose. He exhibited cortical blindness, visual anosognosia, and confabulation upon awakening. Several days later, he experienced acute psychosis and agitation. T2-FSE MRI revealed extensive supratentorial leukoencephalopathy involving both cerebral hemispheres, extending to the posterior corpus callosum due to cerebral anoxia. This case report will discuss different types of encephalopathy from opioid abuse, ABS, visual anosognosia, and confabulation's pathogenic mechanisms. It underscores the necessity of researching substance-induced neuropsychiatric disorders and their pathogenic mechanisms for effective treatments.

Sex-Based Differences in Medicare Reimbursements among Ophthalmologists Persist across Time.

PURPOSE: To evaluate differences in Medicare reimbursements between male and female ophthalmologists between 2013 and 2019. DESIGN: Retrospective cohort study. PARTICIPANTS: Ophthalmologists receiving Medicare reimbursements between 2013 and 2019. METHODS: The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to determine total reimbursements and number of services submitted by ophthalmologists between 2013 and 2019. Reimbursements were standardized to account for geographic differences in Medicare reimbursement per service. Data from the American Community Survey (ACS) were used to determine socioeconomic characteristics (unemployment, poverty, income, and education) by zip code for the location of each physician's practice. A multivariate linear regression model was used to evaluate differences in annual reimbursements by sex, accounting for calendar year, years of experience, total number of services, ACS zip code data, and proportion of procedural services. MAIN OUTCOME MEASURES: Annual Medicare reimbursement and use of billing codes (e.g., outpatient office visits and eye examinations, diagnostic testing, laser treatment, and surgery). RESULTS: Among 20 281 ophthalmologists who received Medicare reimbursements between 2013 and 2019, 15 451 (76%) were men. The most common billing codes submitted were for outpatient visits and eye examinations (13.8 million charges/year), diagnostic imaging of the retina (5.6 million charges/year), intravitreal injections (2.9 million charges/year), and removal of cataract with insertion of lens (2.4 million charges/year). Compared with men, female ophthalmologists received less in median annual reimbursements (median, $94 734.21 [interquartile range (IQR), $30 944.52-$195 701.70] for women vs. $194 176.90 [IQR, $76 380.76-$355 790.80] for men; P < 0.001) and billed for fewer annual median services (median, 1228 [IQR, 454-2433] vs. 2259 [IQR, 996-4075, respectively]; P < 0.001). After adjustment for covariates, female ophthalmologists billed for 1015 fewer services (95% confidence interval [CI], 1001-1029; P < 0.001) and received $20 209.12 less in reimbursements than men (95% CI, -$21 717.57 to -$18 700.66; P < 0.001). CONCLUSIONS: Female ophthalmologists billed for fewer services and received less in reimbursement from Medicare than men over time and across all categories of billing codes. Disparities persisted after controlling for physician and practice characteristics.

Photoreceptor Layer Thinning Is an Early Biomarker for Age-Related Macular Degeneration: Epidemiologic and Genetic Evidence from UK Biobank OCT Data.

PURPOSE: Despite widespread use of OCT, an early-stage imaging biomarker for age-related macular degeneration (AMD) has not been identified. Pathophysiologically, the timing of drusen accumulation in relationship to photoreceptor degeneration in AMD remains unclear, as are the inherited genetic variants contributing to these processes. Herein, we jointly analyzed OCT, electronic health record data, and genomic data to characterize the time sequence of changes in retinal layer thicknesses in AMD, as well as epidemiologic and genetic associations between retinal layer thicknesses and AMD. DESIGN: Cohort study. PARTICIPANTS: Forty-four thousand eight hundred twenty-three individuals from the UK Biobank (enrollment age range, 40-70 years; 54% women; median follow-up, 10 years). METHODS: The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we associated AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age-squared (age2), sex, smoking status, and principal components of ancestry. MAIN OUTCOME MEASURES: Prevalent and incident AMD. RESULTS: Photoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed, whereas retinal pigment epithelium (RPE) and Bruch's membrane (BM) complex thickening started after 57 years of age. Each standard deviation (SD) of PS thinning and RPE-BM complex thickening was associated with incident AMD (PS: hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.23-1.47; P = 3.7 × 10-11; RPE-BM complex: HR, 1.14; 95% CI, 1.06-1.22; P = 0.00024). The AMD PRS was associated with PS thinning (ß, -0.21 SD per twofold genetically increased risk of AMD; 95% CI, -0.23 to -0.19; P = 2.8 × 10-74), and its association with RPE-BM complex was U-shaped (thinning with AMD PRS less than the 92nd percentile and thickening with AMD PRS more than the 92nd percentile). The loci with strongest support for genetic correlation were AMD risk-raising variants Complement Factor H (CFH):rs570618-T, CFH:rs10922109-C, and Age-Related Maculopathy Susceptibility 2 (ARMS2)/High-Temperature Requirement Serine Protease 1 (HTRA1):rs3750846-C on PS thinning and SYN3/Tissue Inhibitor of Metalloprotease 3 (TIMP3):rs5754227-T on RPE-BM complex thickening. CONCLUSIONS: Epidemiologically, PS thinning precedes RPE-BM complex thickening by decades and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage biomarker for future AMD development.

Characteristics of p.Gln368Ter Myocilin Variant and Influence of Polygenic Risk on Glaucoma Penetrance in the UK Biobank.

PURPOSE: MYOC (myocilin) mutations account for 3% to 5% of primary open-angle glaucoma (POAG) cases. We aimed to understand the true population-wide penetrance and characteristics of glaucoma among individuals with the most common MYOC variant (p.Gln368Ter) and the impact of a POAG polygenic risk score (PRS) in this population. DESIGN: Cross-sectional population-based study. PARTICIPANTS: Individuals with the p.Gln368Ter variant among 77 959 UK Biobank participants with fundus photographs (FPs). METHODS: A genome-wide POAG PRS was computed, and 2 masked graders reviewed FPs for disc-defined glaucoma (DDG). MAIN OUTCOME MEASURES: Penetrance of glaucoma. RESULTS: Two hundred individuals carried the p.Gln368Ter heterozygous genotype, and 177 had gradable FPs. One hundred thirty-two showed no evidence of glaucoma, 45 (25.4%) had probable/definite glaucoma in at least 1 eye, and 19 (10.7%) had bilateral glaucoma. No differences were found in age, race/ethnicity, or gender among groups (P > 0.05). Of those with DDG, 31% self-reported or had International Classification of Diseases codes for glaucoma, whereas 69% were undiagnosed. Those with DDG had higher medication-adjusted cornea-corrected intraocular pressure (IOPcc) (P < 0.001) vs. those without glaucoma. This difference in IOPcc was larger in those with DDG with a prior glaucoma diagnosis versus those not diagnosed (P < 0.001). Most p.Gln368Ter carriers showed IOP in the normal range (≤21 mmHg), although this proportion was lower in those with DDG (P < 0.02) and those with prior glaucoma diagnosis (P < 0.03). Prevalence of DDG increased with each decile of POAG PRS. Individuals with DDG demonstrated significantly higher PRS compared with those without glaucoma (0.37 ± 0.97 vs. 0.01 ± 0.90; P = 0.03). Of those with DDG, individuals with a prior diagnosis of glaucoma had higher PRS compared with undiagnosed individuals (1.31 ± 0.64 vs. 0.00 ± 0.81; P < 0.001) and 27.5 times (95% confidence interval, 2.5-306.6) adjusted odds of being in the top decile of PRS for POAG. CONCLUSIONS: One in 4 individuals with the MYOC p.Gln368Ter mutation demonstrated evidence of glaucoma, a substantially higher penetrance than previously estimated, with 69% of cases undetected. A large portion of p.Gln368Ter carriers, including those with DDG, have IOP in the normal range, despite similar age. Polygenic risk score increases disease penetrance and severity, supporting the usefulness of PRS in risk stratification among MYOC p.Gln368Ter carriers.

Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014-2019.

PURPOSE: To characterize trends in use of and expenditure for the intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept, ranibizumab, and bevacizumab among the population enrolled in Original Medicare from 2014 to 2019. METHODS: The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to extract Medicare Part B fee-for-service outpatient injection claims data submitted by ophthalmologists. Multivariable linear regression models were used to evaluate the association between reimbursement, ophthalmologist availability, and agent administration rate. RESULTS: Between 2014 and 2019, 17,588,995 intravitreal injection claims were filed by 4218 US ophthalmologists. Medicare costs for anti-VEGF injections increased from 2.51 B USD in 2014 to 4.02 B USD in 2019. Increased state-level ophthalmologist availability and incremental increases in average reimbursement amounts were found to be significantly associated with a 6.8-fold variation in 2019 overall anti-VEGF injection rates across states. CONCLUSIONS: Medicare injection rates and costs for anti-VEGF injections have both increased between 2014 and 2019, largely driven by increased aflibercept use. There is a significant association between ophthalmologist availability and anti-VEGF injection rate on the state level, suggesting access to care may contribute to the observed state-level disparities in intravitreal injection rates. Further characterization of factors contributing to the state-level variation in injection rates of individual anti-VEGF agents may help inform interventions promoting equitable access to and use of these drugs.

Gender based disparities in Medicare physician reimbursement persist across years and specialty.

Introduction: The gender pay gap is wide in medicine but the extent of this disparity across specialties and over time have not been elucidated. Here we evaluate differences in Medicare reimbursement between men and women physicians over time and by specialty, controlling for physician and practice characteristics. Methods: The Centers for Medicare & Medicaid Services Payment Data was used to determine total reimbursements and number of services submitted by physicians practicing in the US between 2013 and 2019. Data from the American Community Survey (ACS) were used to determine average income, unemployment rates, poverty rates, income, and educational attainment levels by zip code for each physician's practice location. Results: Among the 3,831,504 physicians included in this analysis from 2013-2019, 2,712,545 (70.8%) were men and 1,118,859 (29.2%) were women. Overall, men received more in Medicare reimbursements ($58,815 ± $104,772 vs. $32,205 ± $60,556, p<0.001) and billed more services (864 ± 1,780 vs. 505 ± 1,007, p<0.001) compared to women. The median Medicare reimbursement for men decreased from 2013 to 2019 from $59,710 to $57,874, while the median Medicare reimbursement for women increased from $30,575 to $33,456. Men were reimbursed more than women across all specialties with the greatest disparity in procedure-heavy specialties. The specialties with the highest difference in median Medicare reimbursement between men and women were ophthalmology ($99,452), dermatology ($84,844), cardiology ($64,112), nephrology ($62,352), and pulmonary medicine ($47,399). In linear regression models controlling for calendar year, years of experience, total number of services, and ACS zip-code-level variables, men received a higher amount of Medicare reimbursement in all specialties, as compared to women (p<0.01 for all). The percentage of top earning men (range: 65.0%-99.5%) surpassed the proportion of men in each specialty (range: 46.1%-94.6%), except public health and preventive medicine. Conclusions and Relevance: Women physicians continue to receive lower total Medicare reimbursements than men physicians, particularly in procedure-heavy specialties. Lower clinical volume and fewer procedural services among women physicians partially contribute to the disparities in reimbursement.

Association of retinal optical coherence tomography metrics and polygenic risk scores with cognitive function and future cognitive decline.

PURPOSE: To evaluate the potential of retinal optical coherence tomography (OCT) measurements and polygenic risk scores (PRS) to identify people at risk of cognitive impairment. METHODS: Using OCT images from 50 342 UK Biobank participants, we examined associations between retinal layer thickness and genetic risk for neurodegenerative disease and combined these metrics with PRS to predict baseline cognitive function and future cognitive deterioration. Multivariate Cox proportional hazard models were used to predict cognitive performance. P values for retinal thickness analyses are false-discovery-rate-adjusted. RESULTS: Higher Alzheimer's disease PRS was associated with a thicker inner nuclear layer (INL), chorio-scleral interface (CSI) and inner plexiform layer (IPL) (all p<0.05). Higher Parkinson's disease PRS was associated with thinner outer plexiform layer (p<0.001). Worse baseline cognitive performance was associated with thinner retinal nerve fibre layer (RNFL) (aOR=1.038, 95% CI (1.029 to 1.047), p<0.001) and photoreceptor (PR) segment (aOR=1.035, 95% CI (1.019 to 1.051), p<0.001), ganglion cell complex (aOR=1.007, 95% CI (1.002 to 1.013), p=0.004) and thicker ganglion cell layer (aOR=0.981, 95% CI (0.967 to 0.995), p=0.009), IPL (aOR=0.976, 95% CI (0.961 to 0.992), p=0.003), INL (aOR=0.923, 95% CI (0.905 to 0.941), p<0.001) and CSI (aOR=0.998, 95% CI (0.997 to 0.999), p<0.001). Worse future cognitive performance was associated with thicker IPL (aOR=0.945, 95% CI (0.915 to 0.999), p=0.045) and CSI (aOR=0.996, 95% CI (0.993 to 0.999) 95% CI, p=0.014). Prediction of cognitive decline was significantly improved with the addition of PRS and retinal measurements. CONCLUSIONS AND RELEVANCE: Retinal OCT measurements are significantly associated with genetic risk of neurodegenerative disease and may serve as biomarkers predictive of future cognitive impairment.

Racial Disparities in Glaucoma Vision Outcomes and Eye Care Utilization: An IRIS Registry Analysis.

PURPOSE: To evaluate racial disparities in vision outcomes and eye care utilization among glaucoma patients. DESIGN: Retrospective cohort study. METHODS: In this population-based IRIS Registry (Intelligent Research in Sight) study, we included patients with minimum one diagnosis code for glaucoma at least 6 months prior to January 1, 2015 and at least one eye exam, visual field (VF), optical coherence tomography (OCT), or eye-related inpatient or emergency department (ED) code in 2015. Multivariable logistic and negative binomial regression models were used to assess vision and utilization outcomes, respectively, across race and ethnicity from January 1, 2015 to January 1, 2020. Vision outcomes included cup-to-disc ratio (CDR) progression > 0.80, poor vision (visual acuity 20/200 or worse), low vision codes, and need for glaucoma filtering surgery. Utilization outcomes included outpatient eye exams, OCTs, VFs, inpatient/ED encounters, and lasers/surgeries. RESULTS: Among 996,297 patients, 73% were non-Hispanic White, 15% non-Hispanic Black, 9% Hispanic, 3% Asian/Pacific Islander, and 0.3% Native American/Alaska Native. Compared to White eyes, Black and Hispanic eyes had higher adjusted odds of CDR progression (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.08-1.17; OR = 1.28, 95% CI = 1.22-1.34), poor vision (OR = 1.26, 95% CI = 1.22-1.29; OR = 1.26, 95% CI = 1.22-1.31), glaucoma filtering surgery (rate ratio (RR) = 1.47, 95% CI = 1.42-1.51; RR = 1.13, 95% CI = 1.09-1.18). Hispanic eyes also had increased odds of low vision diagnoses (Hispanic OR = 1.18, 95% CI = 1.07-1.30). Black and Hispanic patients were less likely to have eye exams (RR = 0.94, 95% CI = 0.94-0.95; RR = 0.99, 95% CI = 0.99-0.99) and OCTs (RR = 0.86, 95% CI = 0.85-0.86; RR = 0.97, 95% CI = 0.96-0.98), yet Black patients had higher odds of inpatient/ED encounters (RR = 1.64, 95% CI = 1.37-1.96) compared to White patients. Native American patients were more likely to have poor vision (OR = 1.17, 95% CI = 1.01-1.36) and less likely to have outpatient visits (RR = 0.89, 95% CI = 0.86-0.91), OCTs (RR = 0.85, 95% CI = 0.82-0.89), visual fields (RR = 0.91, 95% CI = 0.88-0.94) or lasers/surgeries (RR = 0.87, 95% CI = 0.79-0.96) compared to White patients. CONCLUSIONS: We found that significant disparities in US eye care exist with Black, Hispanic, and Native American patients having worse vision outcomes and less disease monitoring. Glaucoma may be undertreated in these racial and ethnic minority groups, increasing risk for glaucoma-related vision loss.

Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health.

The human retina is a multilayered tissue that offers a unique window into systemic health. Optical coherence tomography (OCT) is widely used in eye care and allows the noninvasive, rapid capture of retinal anatomy in exquisite detail. We conducted genotypic and phenotypic analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed OCT layer cross-phenotype association analyses (OCT-XWAS), associating retinal thicknesses with 1866 incident conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association studies (GWASs), identifying inherited genetic markers that influence retinal layer thicknesses and replicated our associations among the LIFE-Adult Study (N = 6313). Last, we performed a comparative analysis of phenome- and genome-wide associations to identify putative causal links between retinal layer thicknesses and both ocular and systemic conditions. Independent associations with incident mortality were detected for thinner photoreceptor segments (PSs) and, separately, ganglion cell complex layers. Phenotypic associations were detected between thinner retinal layers and ocular, neuropsychiatric, cardiometabolic, and pulmonary conditions. A GWAS of retinal layer thicknesses yielded 259 unique loci. Consistency between epidemiologic and genetic associations suggested links between a thinner retinal nerve fiber layer with glaucoma, thinner PS with age-related macular degeneration, and poor cardiometabolic and pulmonary function with a thinner PS. In conclusion, we identified multiple inherited genetic loci and acquired systemic cardio-metabolic-pulmonary conditions associated with thinner retinal layers and identify retinal layers wherein thinning is predictive of future ocular and systemic conditions.

Impact of the Affordable Care Act on Glaucoma Severity at First Presentation.

PURPOSE: To test whether the increase in insurance coverage in Massachusetts due to the Affordable Care Act (ACA) is associated with a decrease in glaucoma severity in patients presenting for the first time at a tertiary health system. METHODS: Clinical and billing data of first-time glaucoma patients from a tertiary health system in Massachusetts from 2006 to 2021 was used. Pre-ACA is defined as before 2014 and post-ACA is defined as after 2014. Visual field mean deviation was used to define glaucoma severity: greater than -6 dB, less than -6 dB and greater than -12 dB, and less than -12 dB was classified as "mild," "moderate," and "severe" respectively. Ordinal logistic regression models adjusted for age, race, gender, and insurance type were used to determine the odds of presenting with more severe glaucoma. RESULTS: 2,394 pre-ACA and 3,651 post-ACA first-time glaucoma patients were identified. There was no significant difference in the likelihood of more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.96; 95% CI 0.86-1.08; p=0.49) among the entire population. In stratified analyses, patients who utilized Medicaid for insurance had 52% decreased odds for presenting with more severe glaucoma at first presentation post-ACA compared to pre-ACA (OR=0.48; 95% CI 0.33-0.69; p<0.001). This remained significant after adjustment for age, race, and gender (adjusted OR=0.44; 95% CI 0.29-0.65; p<0.001). CONCLUSION: At a Massachusetts-based tertiary healthcare center, individuals on Medicaid were more likely to have more severe glaucoma at first presentation before the implementation of the ACA, compared to after.

Background polygenic risk modulates the association between glaucoma and cardiopulmonary diseases and measures: an analysis from the UK Biobank.

AIMS: To assess whether associations of cardiopulmonary conditions and markers with glaucoma differ by background genetic risk for primary open angle glaucoma (POAG). METHODS: We constructed a POAG polygenic risk score (PRS) using genome-wide association study summary statistics from a large cross-ancestry meta-analysis. History of glaucoma (including self-report and codes for POAG, 'other glaucoma' or unspecified glaucoma), history of common cardiopulmonary conditions and cardiopulmonary measures were assessed in the UK Biobank. Stratifying by PRS decile 1 (lowest risk) versus decile 10 (highest risk), separate multivariable models were estimated to assess the associations of cardiopulmonary diseases or factors with glaucoma, adjusting for age, sex, smoking and medication use. A Bonferroni correction was used to adjust p values for multiple comparisons. RESULTS: Individuals in POAG PRS decile 1 (417 cases, 44 458 controls; mean age 56.8 years) and decile 10 (2135 cases, 42 413 controls; mean age 56.7 years) were included. Within decile 1, glaucoma cases had significantly higher glycated haemoglobin (38.5 vs 35.9 mmol/mol) and higher prevalence of diabetes (17.5% vs 6.5%), dyslipidaemia (31.2% vs 18.3%) and chronic kidney disease (CKD) (6.7% vs 2.0%) than controls (adjusted p<0.0013 for each). Within decile 10, glaucoma was associated with higher prevalence of dyslipidaemia (27.7% vs 17.3%, p=6.9E-05). The magnitude of association between glaucoma and diabetes, CKD and glycated haemoglobin differed between deciles 1 and 10 (contrast test p value for difference <0.05). CONCLUSION: The relations between systemic conditions and glaucoma vary by underlying genetic predisposition to POAG, with larger associations among those who developed glaucoma despite low genetic risk.

Automated detection of genetic relatedness from fundus photographs using Siamese Neural Networks.

Heritability of common eye diseases and ocular traits are relatively high. Here, we develop an automated algorithm to detect genetic relatedness from color fundus photographs (FPs). We estimated the degree of shared ancestry amongst individuals in the UK Biobank using KING software. A convolutional Siamese neural network-based algorithm was trained to output a measure of genetic relatedness using 7224 pairs (3612 related and 3612 unrelated) of FPs. The model achieved high performance for prediction of genetic relatedness; when computed Euclidean distances were used to determine probability of relatedness, the area under the receiver operating characteristic curve (AUROC) for identifying related FPs reached 0.926. We performed external validation of our model using FPs from the LIFE-Adult study and achieved an AUROC of 0.69. An occlusion map indicates that the optic nerve and its surrounding area may be the most predictive of genetic relatedness. We demonstrate that genetic relatedness can be captured from FP features. This approach may be used to uncover novel biomarkers for common ocular diseases.

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden.

Importance: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. Objective: To evaluate phenotypic features across genetic burden for POAG. Design, Setting, and Participants: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. Main Outcomes and Measures: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. Results: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 µm and macular ganglion cell complex (GCC) of 0.26 µm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). Conclusion and Relevance: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice.

Insights into human health from phenome- and genome-wide analyses of UK Biobank retinal optical coherence tomography phenotypes.

The human retina is a complex multi-layered tissue which offers a unique window into systemic health and disease. Optical coherence tomography (OCT) is widely used in eye care and allows the non-invasive, rapid capture of retinal measurements in exquisite detail. We conducted genome- and phenome-wide analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed phenome-wide association analyses, associating retinal thicknesses with 1,866 incident ICD-based conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association analyses, identifying inherited genetic markers which influence the retina, and replicated our associations among 6,313 individuals from the LIFE-Adult Study. And lastly, we performed comparative association of phenome- and genome- wide associations to identify putative causal links between systemic conditions, retinal layer thicknesses, and ocular disease. Independent associations with incident mortality were detected for photoreceptor thinning and ganglion cell complex thinning. Significant phenotypic associations were detected between retinal layer thinning and ocular, neuropsychiatric, cardiometabolic and pulmonary conditions. Genome-wide association of retinal layer thicknesses yielded 259 loci. Consistency between epidemiologic and genetic associations suggested putative causal links between thinning of the retinal nerve fiber layer with glaucoma, photoreceptor segment with AMD, as well as poor cardiometabolic and pulmonary function with PS thinning, among other findings. In conclusion, retinal layer thinning predicts risk of future ocular and systemic disease. Furthermore, systemic cardio-metabolic-pulmonary conditions promote retinal thinning. Retinal imaging biomarkers, integrated into electronic health records, may inform risk prediction and potential therapeutic strategies.

Effect of visual impairment on depression and anxiety during the COVID-19 pandemic in the United States.

OBJECTIVE: To evaluate associations between visual impairment, anxiety, and depression during the COVID-19 pandemic in the United States. DESIGN: Retrospective cross-sectional design. METHODS: This study included a cohort of U.S. adults enrolled in the National Institutes of Health All of Us Research Program. Individuals who were blind/visually impaired (BVI) were identified via Systematized Nomenclature of Medicine (SNOMED) codes and compared with a control cohort. Prevalences of baseline, new, and worsened depression and anxiety, as defined by SNOMED codes and medication use, were compared between the 2 groups. Anxiety and depression during the COVID-19 pandemic were evaluated using the Generalized Anxiety Disorder 7 and the Patient Health Questionnaire 9 surveys, respectively. RESULTS: A total of 324,915 participants (7526 BVI individuals and 317,389 control individuals) were included. BVI individuals had higher prevalences of baseline anxiety and depression (50.4% vs 28.7%; p < 0.001), new anxiety and depression (0.98% vs 0.66%; p < 0.001), and worsened anxiety and depression throughout the COVID-19 pandemic (0.19% vs 0.07%; p < 0.001) compared with control individuals. Being BVI was significantly associated with baseline and worsened anxiety and depression after controlling for age, sex, race, ethnicity, and comorbidity (adjusted odds ratio [aOR] = 1.61; 95% CI, 1.46-1.78 and aOR = 2.07; 95% CI, 1.03-4.13). Similarly, being BVI was associated with a 2.07 point increase on the Generalized Anxiety Disorder 7 survey (adjusted ß = 2.07; 95% CI, 1.32-3.27) and a 2.96 point increase on the Patient Health Questionnaire 9 survey (adjusted ß = 2.96; 95% CI, 1.64-5.36). CONCLUSIONS: These findings indicate that BVI individuals were disproportionately affected by anxiety and depression at baseline and throughout the pandemic, highlighting an important need to promote access to mental health services among this population.

Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank.

BACKGROUND/AIMS: Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure. METHODS: This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method. RESULTS: Among the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, p<0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31±1.00 SD vs. 0.00±1.00 SD, p<0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles. CONCLUSION: We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.

Exploring COVID-19 Vaccine Hesitancy Amongst Black Americans: Contributing Factors and Motivators.

PURPOSE: To determine reasons for hesitancy towards COVID-19 vaccination and motivators to increase COVID-19 vaccine uptake among Black Americans. DESIGN: Mixed-methods. SETTING: Individual interviews in March-April 2021. PARTICIPANTS: Black adults (20-79 years) who attended a church in Boston, MA and identified as "vaccine hesitant" (n = 18). METHODS: Individual in-depth Zoom interviews to elicit participant views on vaccines in general, specific reasons for COVID-19 vaccine hesitancy, and trusted sources of information. Participants were also asked about possible motivators that could increase COVID-19 vaccine uptake. Transcripts were de-identified and analyzed for major themes using an inductive approach. RESULTS: Analysis included 18 complete interviews. Lack of trust in the government, healthcare, or pharmaceutical companies (n = 18), rushed development (n = 14), fear of side effects (n = 12), history of medical mistreatment (n = 12), and a perception of low risk of disease (n = 9) were the top-cited reasons for COVID-19 vaccine hesitancy. Motivators likely to increase COVID-19 vaccine uptake included more data (n = 17), friends and family getting vaccinated (not celebrities) (n = 11), and increased opportunities that come along with being vaccinated (n = 8). CONCLUSION: There were many reasons for COVID-19 vaccine hesitancy, as reported by participants who were all Black Americans in the Boston area. The public health challenge of increasing vaccine uptake in the Black community is nuanced and intervention efforts may be more successful if delivered by trusted members of the community and tailored to the needs of individuals.

High variability in the measurement of HIV primary prevention activities and outcomes.

INTRODUCTION: While there is a global consensus on monitoring Human Immunodeficiency Virus (HIV) treatment progress, there has been less attention to the degree of consistency of the measurement of HIV prevention programmes-and the global prevention response is not on-track to achieve 2020 goals. In this paper, we assess the degree of variability in primary prevention indicators selected by national strategic plans (NSPs) and global stakeholder monitoring and evaluation (M&E) strategies. METHODS: We obtained the most recent NSPs from low and middle income Joint United Nations Programme on HIV/AIDS (UNAIDS) Fast-Track countries, and M&E documents from The Global Fund to Fight AIDS, Tuberculosis and Malaria (The Global Fund), President's Emergency Plan for AIDS Relief (PEPFAR), UNAIDS, the Global HIV Prevention Coalition and the World Health Organization (WHO). We extracted HIV primary prevention indicators from each document, standardized and aggregated them by age/ sex, categorized indicators by topic, and evaluated the frequency of matched indicators between countries and stakeholders. Data were collected between February and April of 2019. RESULTS: Twenty-one NSPs and five global stakeholder documents were assessed; 736 primary prevention indicators were identified; 284 remained following standardization and aggregation. NSPs contained from 3 to 48 primary prevention indicators, with an average of 23; categories included: HIV education and outreach (17.6%), testing (17.3%) and condom use (16.2%). Of unique national indicators, only 34% was shared between two or more countries. Sixty-nine per cent was applied in a single country only. 56% of NSP indicators did not appear in any global stakeholder document. Conversely, 42% of global indicators did not appear in any surveyed NSPs. Within global indicators, 63% was only measured by one global body, and no single indicator was measured by all five. CONCLUSIONS: These analyses reveal a lack of consensus both between and within countries' and global stakeholders' measurement of HIV prevention. Though some variability is expected, these findings point to a need to refocus attention on achieving greater consensus on a global measurement framework for HIV prevention.