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OBJECTIVE: To describe predominantly persistent subretinal fluid (SRF) in eyes receiving ranibizumab or bevacizumab for neovascular age-related macular degeneration and compare visual acuity (VA) to eyes with non-persistent SRF. DESIGN: Cohort within randomized clinical trial PARTICIPANTS: Comparison of Age-related Macular Degeneration Treatments Trials patients assigned to pro re nata (PRN) treatment. METHODS: Reading center graders evaluated optical coherence tomography scans at baseline and monthly follow-up visits for SRF. Predominantly persistent SRF through week 12 was defined as SRF at baseline, weeks 4, 8, and 12. Predominantly persistent SRF through 1 or 2 years was defined as SRF in ≥80% of visits by year 1 or year 2, respectively. Adjusted mean VA score and VA change from baseline were compared between eyes with predominantly persistent SRF and eyes non-persistent SRF over the same duration using linear regression models including baseline predictors of VA and predominantly persistent intraretinal fluid (IRF). PRIMARY OUTCOME MEASURES: Predominantly persistent SRF through year 1, adjusted VA score and VA change, and SRF thickness at the foveal center. RESULTS: Among 406 eyes with baseline SRF, SRF persisted in 108 (26.6%) through week 12, 94 (23.2%) through year 1, and 77 (19.0%) through year 2. Adjusted VA means (letters) at year 1 were similar between eyes with predominantly persistent vs. non-persistent SRF by week 12, (68.1 vs. 70.2; P=0.18), year 1 (67.6 vs. 70.2; P=0.11), and year 2 (71.4 vs. 70.9; P=0.78). Adjusted change in VA at year 1 means were similar between eyes with predominantly persistent vs. non-persistent SRF by week 12 (6.3 vs. 7.6; P=0.38), year 1 (5.5 vs. 7.8; P=0.14), and year 2 (8.1 vs. 7.7; P=0.78). Among eyes with predominantly persistent SRF through year 1, SRF was absent in the foveal center in 46 (48.9%), thickness was 1-200 μm in 48 (50.0%) and >200 μm in 1 (1.1%) at year 1. CONCLUSIONS: Eyes with predominantly persistent and non-persistent SRF through week 12, year 1, or year 2 had similar VA outcomes after adjustment for baseline covariates and persistent IRF. At the foveal center, predominantly persistent SRF was most commonly absent or present in small quantities.

BackgroundFinancial compensation of research participants has been standard practice for centuries, however, there is an ongoing debate among researchers and ethicists regarding the ethical nature of this practice. While these debates develop ethical arguments and theories, they fail to incorporate input from those most affected by financial compensation: potential research participants.MethodsTo identify attitudes surrounding clinical research, participants of a long-standing cohort completed a one-time interview. Open-ended questions stimulated a participant-driven discussion surrounding medical research. Following a grounded theory methodology, 58 semistructured interview transcripts were coded, focusing on attitudes surrounding financial compensation of research participants.ResultsOf the interviews coded, the majority of participants identified as Black/African American (n=44) and were women (n=40). Five major themes emerged. In support of financial compensation, participants felt that study participants should be compensated for time, effort and risk. However, participants were concerned that compensation may differentially impact low-income populations and entice them to hide potentially harmful side effects. Participants also mentioned that financial compensation may invalidate study results if participants knowingly provide false information to subvert inclusion/exclusion criteria.ConclusionThe emergence of both positive and negative themes reiterates the complicated issue of providing financial compensation for study participation. While compensation as a motivator for research participation raises ethical concerns, participants discussed weighing the benefits with the risks in order to make an informed decision. To avoid paternalistic behaviours, research staff must allow potential research participants to review the available information and make the decision that best reflects their wishes.

To identify precursors of macular atrophy (MA) and of fibrotic scar (FS) in eyes treated with anti-vascular endothelial growth factor through pixel-mapping analysis of baseline optical coherence tomography (OCT).Design: Cross-sectional analysis.Multicenter clinical trial.68 eyes from the Comparison of Age-Related Macular Degeneration Treatments Trials.Treatment with anti-vascular endothelial growth factor agents.The percentage of MA or FS pixels with each OCT feature at baseline, and the odds ratio for baseline pixels with an OCT feature to develop MA or FS.Retinal pigment epithelium atrophy and photoreceptor loss on OCT were highly predictive of MA at that location at years 2 and 5 (P.0001), but accounted for only 22.5% of the ensuing atrophy at year 2 and less at year 5. Among pixels of MA at year 2, 78% were preceded by thick drusen, 54% by subretinal macular neovascularization (MNV), and 22.5% by no detectable OCT features. MNV, subretinal hyperreflective material, pigment epithelial detachment, intraretinal fluid, and sub-retinal pigment epithelium fluid were predictive of FS at that location (P values.05). More than 75% of the pixels of FS at years 2 and 5 were preceded by pixels of baseline MNV.Most pixels of FS were preceded by components of neovascularization. Although one-quarter of MA was accounted for by pre-existing evidence of atrophy on OCT alone, the development of MA in areas of thick drusen, areas with and without subretinal MNV lesion, and areas without detectable OCT precursors argues that the development of MA is multifactorial and may follow, in part, a non-neovascular pathway.

Purpose Alpha lipoic acid (ALA) is a nutraceutical and potent antioxidant that has shown efficacy in the retina light damage mouse model and in humans for multiple sclerosis. Our objective was to evaluate the efficacy and safety of oral ALA for the treatment of geographic atrophy (GA). Design Randomized, controlled, double-masked, multicenter phase 2 clinical trial of ALA versus placebo. Participants Participants with unilateral or bilateral GA from age-related macular degeneration. Methods Participants were randomized to 1200 mg daily of ALA or placebo. Fundus autofluorescence, fundus color photography, and spectral-domain OCT were conducted and best-corrected visual acuity (BCVA) was obtained at baseline and every 6 months through month 18. Main Outcome Measures Annual rate of change over 18 months in square root-transformed area of GA in study eyes as measured on fundus autofluorescence. Secondary outcomes included the number of adverse events (AEs), change in BCVA, and annual rate of change in area of GA measured on color photographs. Results Fifty-three participants (mean age, 80 years) were randomized (April 2016–August 2017). Twenty-seven participants (37 eyes) were in the placebo group, and 26 participants (36 eyes) were in the ALA group. Unadjusted mean (standard error) annual change in GA area was 0.28 (0.02) mm and 0.31 (0.02) mm for the placebo and ALA groups, respectively (difference, 0.04 mm; 95% confidence interval [CI], –0.03 to 0.11 mm; P = 0.30). Adjusting for baseline GA area, number of GA lesions, and presence of subfoveal GA, the mean annual change in GA area was 0.27 (0.04) mm and 0.32 (0.05) mm for the placebo and ALA groups, respectively (difference, 0.05 mm; 95% CI, –0.02 to 0.12 mm; P = 0.14). At 18 months, the percent of eyes losing 15 letters or more of BCVA was 22% (8 of 36) and 14% (5 of 36) in the placebo and ALA groups, respectively (P = 0.54). No difference was found in the percentage of participants with nonserious AEs (P = 0.96) or serious AEs (P = 0.28) between the placebo and ALA groups. Conclusions Results do not support ALA having beneficial effects on GA or BCVA. This trial design may be useful for other GA repurposing drug trials.

Objective To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment. Design Multicenter, randomized clinical trial. Participants Patients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial. Interventions At enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment. Main Outcome Measures Mean change in visual acuity. Results Among patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, −1.4 letters; 95% confidence interval [CI], −3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, −2.4 letters; 95% CI, −4.8 to −0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P P = 0.03) and a lower proportion without fluid (−19%; P P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07−1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF). Conclusions Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The city of Philadelphia has long been criticized for the amount of litter strewn about its streets. To more fully understand this problem, a recent city initiative, the Clean PHL program, sent out individuals to rate the amount of litter on more than 28,000 blocks across the city. We used multilevel models to analyze these data to identify both address-level and block group–level correlates of increased litter ratings. The results show that being on an arterial or collector street, the late summer and early fall seasons, and exposure to food-serving businesses and vacant properties are linked with the odds of increased litter, whereas proximity to a park is linked with decreased litter. We also found that increased block group–level disadvantage is directly related to increased litter and serves to moderate the relationships between some address-level predictors and litter.

Purpose To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression. Design Consensus meeting. Participants Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. Methods As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA. Main Outcome Measures Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates. Results OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA. Conclusions An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated.

BACKGROUND: Verbal short-term memory (STM) and the related ability, working memory (WM), are widely understood to be integral components of language production and comprehension. However, assessment of these abilities in people with aphasia is hampered by a lack of valid, standardized measures that are clinically appropriate. Focusing primarily on verbal STM, we held a series of five focus groups with speech-language pathologists (SLPs) to understand better their current clinical practices and their beliefs and attitudes regarding assessment of verbal STM in aphasia. AIMS: The purpose of this study was to explore the attitudes, beliefs and preferences of clinical SLPs to determine: (1) current practices related to verbal STM assessment; (2) the extent to which practices reflect current theories of aphasia and the role of verbal STM in language processing; and (3) practical considerations regarding aphasia assessment in clinical practice. METHODS & PROCEDURES: Five focus groups were conducted using a semi-structured interview protocol with a total of 44 SLPs. Grounded theory methodology was used to collect, code and analyse the data. Codes were reviewed to identify emerging themes. Themes were compared to explore meta-themes, connections and potential theoretical frameworks. OUTCOMES & RESULTS: Five main themes were identified: (1) The theoretical understanding that clinical SLPs have regarding the role of verbal STM in aphasia is not always consistent with clinical practice; (2) Clinical SLPs highly value functionally relevant assessments; (3) The intense time constraints in clinical practice affect all aspects of assessment; (4) Clinical SLPs feel that there is a lack of appropriate tests for assessment of STM in aphasia; and (5) Clinical SLPs prefer tests that are comprehensive, easy to administer and psychometrically sound. CONCLUSIONS: Clinical SLPs report a lack of standardized measures to assess STM in individuals with aphasia. Researchers are met with several challenges in the development of these tests including effective communication with clinicians regarding the benefit of verbal STM assessments, especially as it relates to functional skills, and the creation of a test that is comprehensive yet simple, quick and easy to administer.

Despite a myriad of potential pathways linking neighborhood change and gentrification to health, existing quantitative measures failed to capture individual-level, self-reported perceptions of these processes. We developed the Perceptions About Change in Environment and Residents (PACER) survey to measure the gentrification-related neighborhood change experienced by individuals relevant to health. We employed a multi-stage process to develop PACER including a scoping review, question refinement, content validity, and cognitive interviews. Content validity and cognitive interviews were assessed within the National Neighborhood Indicators Partnership (NNIP) and for residents of different tenure in both gentrifying and non-gentrifying neighborhoods to ensure PACER considers the complex nature of neighborhood change for different people within different urban contexts. We piloted the instrument to a sample from the resident panel BeHeardPhilly to assess acceptability and data quality. Finally, we assessed internal consistency, dimensionality, and criterion-related validity using Principal Components Analysis (PCA), descriptive statistics, and correlation coefficients. Testing showed good internal consistency for PACER questions, as well as for each of four resulting factors (Feelings, Built Environment, Social Environment, and Affordability). Correlations between factors and other context measures demonstrated strong criterion-related validity. PACER offers an unprecedented tool for measuring and understanding resident perceptions about gentrification-related neighborhood change relevant to health. Rigorously tested and tailored for health, PACER holds utility for application across different settings to examine changes from events that may impact and shift neighborhoods., Highlights • New survey tool of neighborhood change and gentrification is presented. • This validation study found strong construct validity and reliability. • Measures can be used to study the impacts of neighborhood change on health of residents.

Purpose To describe changes in visual acuity (VA) and macular morphologic features at 5 years in eyes with nonfibrotic scar (NFS) identified at 1 year in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Design Prospective cohort study within a randomized clinical trial. Participants Participants in CATT. Methods Participants assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens were released from the clinical trial protocol after 2 years and recalled at 5 years. Nonfibrotic scar was identified on color images at year 1 as flat, small, well-circumscribed areas of pigmentation with varying degrees of central hypopigmentation without exposure of underlying choroidal vessels at the site of baseline choroidal neovascularization. Follow-up images were assessed for changes in and around NFS. Main Outcome Measures Pigmentation changes, VA, development of fibrotic scar (FS), nongeographic atrophy (NGA), geographic atrophy (GA), retinal fluid on OCT, and fluorescein leakage. Results Among 474 eyes with images obtained at 1, 2, and 5 years, 39 (8.2%) showed NFS at 1 year with a mean VA of 80 letters (Snellen equivalent, 20/25). Among these eyes, FS developed in 5% at 2 years and 28% at 5 years. Nongeographic atrophy was observed in 34%, 47%, and 65% of eyes at 1, 2, and 5 years, respectively. Geographic atrophy developed in 5% of eyes at 2 years and 21% at 5 years. Among eyes with NFS, FS, or no scar at 1 year, mean VA at 5 years was 73 letters (20/32), 48 letters (20/100), and 62 letters (20/63), respectively. At 5 years, NFS eyes demonstrated less GA, less intraretinal fluid, more subretinal fluid, and less subretinal pigment epithelium fluid (all P 0.50). The proportion of eyes with fluid on OCT also did not change (P = 0.36). Subretinal hyperreflective material disappeared by 5 years in 40% of eyes with NFS. Conclusions These results indicate that, on average, eyes with NFS after anti-VEGF treatment have good VA not only at 1 and 2 years, but also through 5 years.

To examine the use and association of medications for opioid use disorder (MOUD) with treatment completion and retention for criminal justice referred (CJR) admissions to residential treatment.A retrospective analysis of the Treatment Episode Dataset-Discharge (TEDS-D; 2015-2018) for adults (N = 205,348) admitted to short-term (ST) (30 days) or long-term (LT) (30 days) residential treatment for OUD. Outcomes were MOUD in treatment plans, and treatment completion and retention (ST10 days; LT90 days). Logistic regression analyses were conducted separately for ST and LT settings.CJR admissions were less likely to have MOUD than non-CJR admissions (ST, 11% vs. 21%; LT, 10% vs. 24%, respectively) and were more likely to complete and be retained in treatment. In ST settings, MOUD was associated with higher likelihood of treatment completion and retention. In LT settings, MOUD was associated with higher likelihood of treatment retention and lower likelihood of treatment completion. These associations tended to be slightly weaker for CJR admissions, with the exception of treatment completion in LT settings, but the moderating effect size of CJR status in all models was very small. Small differences in the moderating effect of CJR status by race and ethnicity were observed in LT settings.MOUD is greatly under-utilized for CJR patients, and given that MOUD was associated with positive outcomes, there is a critical need to find ways to increase access to MOUD for CJR patients in residential treatment. Race and ethnicity appear to have relatively little impact on outcomes.

BackgroundThiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).MethodsSecondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models.ResultsPatients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference −6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference −75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference −41.9 um; p=0.001) and year 2 (difference −43.3 um; p=0.001).ConclusionsIn this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones.Trial registration numberClinicalTrials.gov NCT00593450.

PURPOSE: To determine associations of systemic medications with the incidence and growth of geographic atrophy (GA) in participants of the comparison of age-related macular degeneration treatments trials. METHODS: Participants of comparison of age-related macular degeneration treatments trials with new untreated choroidal neovascularization in the study eye (one study eye per participant) were randomized to receive treatment with bevacizumab or ranibizumab. Participants were released from clinical trial treatment at 2 years and examined at approximately 5 years. Color fundus photographs and fluorescein angiograms taken at baseline, Years 1, 2, and 5 were assessed for the presence and size of GA by two masked graders. Participants were interviewed about systemic medication use at baseline. Systemic medications previously reported to be associated with age-related macular degeneration were evaluated for associations with GA incidence in study eye using univariable and multivariable Cox models and for association with the GA growth using linear mixed effects models. RESULTS: In multivariable analysis of 1,011 study eyes without baseline GA, systemic medications, including cholinesterase inhibitors, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, diuretics, aspirin, steroids, statins, hormone replacement therapy, antacids, and drugs targeting G protein-coupled receptors, were not associated with GA incidence in the study eye (all adjusted hazard ratios ≤1.86, P ≥ 0.18). In multivariable analysis of 214 study eyes with longitudinal GA size measurements, calcium channel blockers were associated with a higher GA growth rate (0.40 vs. 0.30 mm/year, P =0.02). CONCLUSION: None of the systemic medications analyzed were associated with GA incidence. However, calcium channel blockers were associated with a higher growth rate of GA in the study eye.

Purpose To determine associations between beta-peripapillary atrophy (B-PPA) and incidence and growth of geographic atrophy (GA) in eyes treated with anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Methods We included 245 cases with incident GA and 245 controls matched by baseline demographics and characteristics associated with development of GA in the CATT. Baseline color images were graded for the type of B-PPA, defined as presence of hypopigmentation with visible choroidal vessels and sclera that is adjacent to the optic disk. Beta-peripapillary atrophy was further classified as scleral ring, sclera, sclera/choroidal blood vessels, or combination. Areas of each type of B-PPA and the circumferential extent of B-PPA were measured. Results Beta-peripapillary atrophy was present in 58% of eyes developing GA and in 52% without GA (P = 0.17). The greater circumferential extent of sclera/choroidal blood vessels B-PPA in relation to the optic disk was associated with incident GA (P = 0.02) and the GA size at first observation (P = 0.047). Beta-peripapillary atrophy was not associated with GA growth rates (P>0.05). Patients without B-PPA had a higher number of GA-associated risk alleles of ARMS2 (P = 0.0003) and HTRA1 (P = 0.001). Conclusion The extent of sclera/choroidal blood vessel B-PPA was associated with the GA incidence and size but not with the growth rate in eyes treated for neovascular age-related macular degeneration. Beta-peripapillary atrophy and GA may share some common pathophysiologic pathways unrelated to the GA-associated risk alleles evaluated.

IMPORTANCE: Retinal hypopigmentation and hyperpigmentation are precursors of geographic atrophy (GA). Incidence and progression to GA in eyes treated with anti–vascular endothelial growth factor for neovascular age-related macular degeneration (nAMD) have not been investigated. OBJECTIVE: To determine the incidence and progression of non-GA (NGA) and associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: This study is a post hoc analysis of a cohort study within the Comparison of Age-Related Treatments Trials (CATT) clinical trial. Participants were recruited February 20, 2008, through December 9, 2009; released from protocol follow-up and treatment after 2 years; and recalled from March 14, 2014, through March 31, 2015. Data analyses were conducted from January 11, 2019, through November 27, 2019. INTERVENTIONS: Participants were randomized to ranibizumab or bevacizumab for (1) 2 years of monthly or as-needed injections or (2) monthly injections for 1 year and as-needed injections the following year. Participants were treated according to best medical judgement thereafter. MAIN OUTCOMES AND MEASURES: Incidence of nAMD-associated NGA (hypopigmentation and hyperpigmentation in color images) and progression; adjusted risk ratios (aRR) for baseline characteristics. RESULTS: Among 1107 participants, risk of NGA was 35% (391 eyes), 59% (246 eyes), and 81% (122 eyes) at 1, 2, and 5 years, respectively. Risk factors for NGA included worse visual acuity (20/200-20/320: aRR, 1.74 [95% CI, 1.24-2.43], compared with ≤20/40; P = .006), larger neovascularization area (>4 disc areas: aRR, 1.31 [95% CI, 1.01-1.71], compared with ≤1 disc areas; P = .007), switched drug regimen (aRR, 1.28 [95% CI, 1.06-1.54], compared with as-needed injections; P = .02), and single-nucleotide variants Age-Related Maculopathy Susceptibility 2 (ARMS2) (TT variant: relative risk [RR], 1.53 [95% CI, 1.22-1.93]; P = .001) and HtrA Serine Peptidase 1 (HTRA1) (AG variant: RR, 1.23 [95% CI, 1.01-1.48]; AA variant: RR, 1.51 [95% CI, 1.20-1.91]; P = .002). Sub–retinal pigment epithelium thickness was protective (>275 μm: aRR, 0.59 [95% CI, 0.46-0.75], compared with ≤75 μm; P

We examine how the densities of adult and juvenile drug offenders within neighborhoods might be linked to the odds of juvenile recidivism due to drug sales and drug possession. To do so, we analyze a dataset of 5,528 juvenile offenders adjudicated in Philadelphia’s Family Court between 1996 and 2004 using multilevel models to estimate the effects of both individual- and neighborhood-level indicators on the odds of recidivism. The results indicate that community context is significantly related to the odds of juvenile recidivism due to drug sales, but not due to drug possession. Neighborhood levels of adult and juvenile drug offender densities are also shown to moderate the links between individual-level characteristics and the odds of juvenile drug sales recidivism.

PURPOSE: To determine baseline predictors of visual acuity (VA) outcomes at 5 years after initiating treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD). DESIGN: Secondary analysis of data from a cohort study. PARTICIPANTS: Patients enrolled in the Comparison of AMD Treatments Trials (CATT) who completed a 5-year follow-up visit. METHODS: Participants were randomly assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After two years, patients were released from the clinical trial protocol, and were recalled for examination at 5 years. Trained readers evaluated baseline lesion features, fluid and thickness. Baseline predictors were determined using univariate and multivariate regression analysis. MAIN OUTCOME MEASURES: VA score and change from baseline, ≥3-line gain, and VA 20/200 or worse at 5 years. RESULTS: Among 647 patients with VA measured at 5 years, mean VA score in the study eye was 58.9 letters (≈20/63), mean decrease from baseline was 3.3 letters, 17.6% eyes gained ≥3 lines, and 19.9% had VA of 20/200 or worse. In multivariate analysis, worse baseline VA was associated with worse VA, more VA gain, higher percentage with ≥3-line gain, and higher percentage with 20/200 or worse at 5 years (all p

Patients with chronic kidney diseases (CKDs) are at risk for further loss of kidney function and death, which occur despite reasonable blood pressure treatment. To determine whether arterial stiffness influences CKD progression and death, independent of blood pressure, we conducted a prospective cohort study of CKD patients enrolled in the CRIC study (Chronic Renal Insufficiency Cohort). Using carotid–femoral pulse wave velocity (PWV), we examined the relationship between PWV and end-stage kidney disease (ESRD), ESRD or halving of estimated glomerular filtration rate, or death from any cause. The 2795 participants we enrolled had a mean age of 60 years, 56.4% were men, 47.3% had diabetes mellitus, and the average estimated glomerular filtration rate at entry was 44.4 mL/min per 1.73 m 2 . During follow-up, there were 504 ESRD events, 628 ESRD or halving of estimated glomerular filtration rate events, and 394 deaths. Patients with the highest tertile of PWV (>10.3 m/s) were at higher risk for ESRD (hazard ratio [95% confidence interval], 1.37 [1.05–1.80]), ESRD or 50% decline in estimated glomerular filtration rate (hazard ratio [95% confidence interval], 1.25 [0.98–1.58]), or death (hazard ratio [95% confidence interval], 1.72 [1.24–2.38]). PWV is a significant predictor of CKD progression and death in people with impaired kidney function. Incorporation of PWV measurements may help define better the risks for these important health outcomes in patients with CKDs. Interventions that reduce aortic stiffness deserve study in people with CKD.

BACKGROUND AND AIMS: Coronary artery calcification (CAC) is common among patients with chronic kidney disease (CKD) and predicts the risk for cardiovascular disease (CVD). We examined the associations of novel risk factors with CAC progression among patients with CKD. METHODS: Among 1,123 CKD patients in the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured in Agatston units at baseline and a follow-up visit using electron beam computed tomography or multidetector computed tomography. RESULTS: Over an average 3.3-year follow-up, 109 (25.1%) participants without CAC at baseline had incident CAC and 124 (18.0%) participants with CAC at baseline had CAC progression, defined as an annual increase of ≥100 Agatston units. After adjustment for established atherosclerotic risk factors, several novel risk factors were associated with changes in CAC over follow-up. Changes in square root transformed CAC score associated with 1 SD greater level of risk factors were −0.20 (95% confidence interval, −0.31 to −0.10; p

Purpose To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Design Consensus meeting. Participants Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. Methods As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. Main Outcome Measures A consensus classification system for atrophy and OCT-based criteria to identify atrophy. Results OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. Conclusions A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

PURPOSE: To summarize the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (AMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials. DESIGN: Systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings. PARTICIPANTS: A panel of retina specialists. METHODS: During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases. A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular AMD was held. MAIN OUTCOME MEASURES: Advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced AMD trials. RESULTS: Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus autofluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution optical coherence tomography volume scans. These images should be acquired at regular intervals throughout the study. In studies of non-neovascular AMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit. Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study. Indocyanine-green angiography (ICG-A) may be considered at baseline under certain conditions. For studies in patients with neovascular AMD, increased need for visualization of the vasculature must be taken into account. Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions. CONCLUSIONS: A multimodal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features. Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future.

PurposeChronic kidney disease (CKD) patients often develop cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess the association between progression of retinopathy and concurrent incidence of CVD events in participants with CKD.DesignWe assessed 1051 out of 1936 participants in the Chronic Renal Insufficiency Cohort Study that were invited to have fundus photographs obtained at two timepoints separated by 3.5 years, on average.MethodsUsing standard protocols, presence and severity of retinopathy (diabetic, hypertensive or other) and vessel diameter calibre were assessed at a retinal image reading centre by trained graders masked to study participants’ information. Participants with a self-reported history of CVD were excluded. Incident CVD events were physician adjudicated using medical records and standardised criteria. Kidney function and proteinuria measurements along with CVD risk factors were obtained at study visits.ResultsWorsening of retinopathy by two or more steps in the EDTRS retinopathy grading scale was observed in 9.8% of participants, and was associated with increased risk of incidence of any CVD in analysis adjusting for other CVD and CKD risk factors (OR 2.56, 95% CI 1.25 to 5.22, pConclusionProgression of retinopathy is associated with higher incidence of CVD events, and retinal-vascular pathology may be indicative of macrovascular disease even after adjustment for kidney diseases and CVD risk factors. Assessment of retinal morphology may provide important information when assessing CVD in patients with CKD.

Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration.A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplements. Trained readers evaluated retinal/subretinal hemorrhage in baseline fundus photographs. Adjusted odds ratios from multivariate logistic regression models assessed the association between iron use and baseline hemorrhage adjusted by age, sex, smoking, hypertension, anemia, and use of antiplatelet/anticoagulant drugs.Among 1,165 participants, baseline retinal/subretinal hemorrhage was present in the study eye in 71% of 181 iron users and in 61% of 984 participants without iron use (adjusted odds ratio = 1.47, P = 0.04), and the association was dose dependent (adjusted linear trend P = 0.048). Iron use was associated with hemorrhage in participants with hypertension (adjusted odds ratio = 1.87, P = 0.006) but not without hypertension. The association of iron use with hemorrhage remained significant among hypertensive participants without anemia (adjusted odds ratio = 1.85, P = 0.02).Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose-response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.

Importance Recent reports suggest that cilioretinal arteries (CRAs) confer protection against developing advanced age-related macular degeneration (AMD). Objective To further characterize the association between the presence of a CRA and incidence of geographic atrophy (GA) or choroidal neovascularization (CNV). Design This cohort study constituted an ad hoc secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and was performed at 44 clinical centers in the United States among participants in CATT with CNV in the study eye and without advanced AMD in the fellow eye at baseline. The presence of a CRA was determined by 2 graders, masked to clinical data, using color fundus photographs, red-free fundus photographs, and fluorescein angiography. The proportion with CRAs at baseline between the study eye with CNV and fellow eye without CNV was first compared. The association of a CRA with incidence of CNV or GA at 5 years among fellow eyes and with incidence of GA among study (treated) eyes was then assessed. In addition, the association of CRAs with the Age-Related Eye Disease Study severity scale among the fellow eyes at baseline was assessed. Data were collected from February 1, 2008, through April 30, 2015, and analyzed from July 1, 2018, through April 30, 2019. Exposures Presence of a CRA. Main Outcomes and Measures The association between the presence of a CRA and incidence of CNV or GA at 5 years of follow-up. Results A total of 350 patients (700 eyes) (230 [65.7% women; mean [SD] age, 77 [7.2] years) were included in the analysis. Cilioretinal arteries were present in 67 of 345 (19.4%) fellow eyes without baseline CNV and 73 of 349 (20.9%) study eyes with baseline CNV (P = .60). Cilioretinal arteries in fellow eyes were not associated with incidence of CNV at 5 years (125 of 278 [45.0%] among eyes without CRAs and 30 of 67 [44.8%] among eyes with CRAs;P = .99) or with incidence of GA at 5 years (110 of 278 [39.6%] among eyes without CRAs and 25 of 67 [37.3%] among eyes with CRAs;P = .89). Cilioretinal arteries in study eyes were not associated with incidence of GA at 5 years (105 of 276 [38.0%] study eyes without CRAs and 26 of 73 [35.6%] study eyes with CRAs;P = .72). Conclusions and Relevance The analysis did not find a protective association between CRAs and incidence of CNV or GA among CATT participants who had unilateral exudative AMD. Why these findings were different from those of previous publications is unclear but may be partially explained by the different techniques used to detect CRAs or by the baseline advanced disease in CATT participants. Trial Registration ClinicalTrials.gov identifier:NCT00593450

Importance Associations between retinopathy and kidney disease have been previously described. The association between the progression of retinopathy and concurrent progression of chronic kidney disease is unknown. Objective To assess the association between progression of retinopathy and concurrent progression of chronic kidney disease (CKD) among persons with CKD enrolled in a prospective cohort study. Design, Setting, and Participants A total of 1936 patients with chronic kidney disease enrolled in the multicenter, prospective Chronic Renal Insufficiency Cohort (CRIC) Study were invited to have 2 nonmydriatic fundus photography sessions separated by a mean (SD) of 3.5 (0.5) years. The study was conducted from May 12, 2006, to June 29, 2011. Data analysis was performed from March 16, 2016, to November 17, 2017. Main Outcomes and Measures Fundus photographs obtained at baseline and then at a follow-up at 3.5 years were reviewed by masked graders for presence and severity of retinopathy, and vessel calibers were assessed using standard protocols. The associations of the changes in retinal features with progression of CKD (50% estimated glomerular filtration rate [eGFR] loss or incident end-stage renal disease, and differences in eGFR slope in the same time period) were assessed with univariable and multivariable logistic regression models. Results Among 1583 CRIC participants who had baseline fundus photography, had additional follow-up in CRIC, and were at risk for retinopathy progression, 1025 patients (64.8%) had follow-up photography. The odds ratio (OR) for CKD progression associated with worsening of retinopathy in comparison with participants with stable retinopathy was 2.24 (95% CI, 1.28-3.91;P = .005) in univariable analysis among participants with baseline and follow-up photography. In the multivariable analysis, the OR was 1.62 (95% CI, 0.77-3.39;P = .20). The multiple imputation analysis provided similar results. Conclusions and Relevance Progression of retinopathy appears to be associated with progression of CKD on univariable analysis but not on multivariable analysis suggesting that similar risk factors may be affecting the progression of both retinal and chronic kidney disease.

Purpose To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD). Design Cohort study. Participants Patients enrolled in the Comparison of AMD Treatments Trials. Methods Patients were assigned randomly to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At 5 years, patients were recalled for examination. Main Outcome Measures Visual acuity (VA) and morphologic retinal features. Results Visual acuity was obtained for 647 of 914 (71%) living patients with average follow-up of 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments was 15.4. Most patients (60%) were treated 1 time or more with a drug other than their assigned drug. At the 5-year visit, 50% of eyes had VA of 20/40 or better and 20% had VA of 20/200 or worse. Mean change in VA was −3 letters from baseline and −11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm 2 , a mean of 4.8 mm 2 larger than at 2 years. Geographic atrophy was present in 213 of 515 (41%) gradable eyes and was subfoveal in 85 eyes (17%). Among 555 eyes with spectral-domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% sub–retinal pigment epithelium). Mean foveal total thickness was 278 μm, a decrease of 182 μm from baseline and 20 μm from 2 years. The retina was abnormally thin ( P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups. Conclusions Vision gains during the first 2 years were not maintained at 5 years. However, 50% of eyes had VA of 20/40 or better, confirming anti–vascular endothelial growth factor therapy as a major long-term therapeutic advance for neovascular AMD.

Purpose To evaluate the association between pseudodrusen and incidence of late age-related macular degeneration (AMD) in fellow eyes of patients with unilateral neovascular AMD (nAMD). Design Cohort study within the Comparison of AMD Treatments Trials (CATT). Participants Patients with neither nAMD nor geographic atrophy (GA) in the fellow eye at baseline. Methods Presence and type (dot, reticular, or confluent) of baseline pseudodrusen were assessed using digital color fundus photography (CFP) viewed under full color, green channel, and blue channel; red-free images; and fluorescein angiography (FA). Incidence of nAMD was based on monthly clinical examination and reading center evaluation of images at years 1 and 2. Incidence of GA was based on reading center evaluation of CFP and FA images at years 1 and 2. Associations of baseline pseudodrusen with incident nAMD and GA were summarized with adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs) from multivariate Cox models, with adjustment of covariates identified through backward stepwise selection. Main Outcome Measures Incident nAMD and GA. Results Among 620 fellow eyes, 176 (28.4%) had baseline pseudodrusen (55% dot, 82% reticular, 35% confluent). Within 2 years, nAMD occurred in 54 eyes (30.7%) with pseudodrusen and in 72 eyes (16.2%) without pseudodrusen (aRR, 2.05; 95% CI, 1.43–2.93); GA occurred in 27 eyes (15.3%) with pseudodrusen and in 37 eyes (8.3%) without pseudodrusen (aRR, 1.89; 95% CI, 1.13–3.17); late AMD occurred in 73 eyes (41.5%) with pseudodrusen and in 101 eyes (22.8%) without pseudodrusen (aRR, 2.07; 95% CI, 1.51–2.83). Dot pseudodrusen were associated independently with nAMD (aRR, 2.53; 95% CI, 1.60–4.00), whereas confluent pseudodrusen were associated independently with GA (aRR, 4.35; 95% CI, 1.69–11.2). Eyes with pseudodrusen had increased incidence of late AMD regardless of whether the Age-Related Eye Diseases Study (AREDS) severity score was 2 (28.7% vs. 10.3%), 3 (34.9% vs. 13.7%), or 4 (50.5% vs. 32.0%). Conclusions In fellow eyes of CATT participants, pseudodrusen were associated independently with a higher incidence of both nAMD and GA. Dot pseudodrusen were associated with nAMD, whereas confluent pseudodrusen were associated with GA. Pseudodrusen should be considered along with the AREDS severity score for predicting late AMD.

To describe morphologic and visual outcomes in eyes with angiographic cystoid macular edema (CME) treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (nAMD).Prospective cohort study within a randomized clinical trial.A total of 1185 CATT study subjects.Baseline fluorescein angiography (FA) images of all CATT study eyes were evaluated for CME. Grading of other characteristics on optical coherence tomography (OCT) and photographic images at baseline and during 2-year follow-up was completed by readers at the CATT Reading Centers. Three groups were created on the basis of baseline CME and intraretinal fluid (IRF) status: (1) CME, (2) IRF without CME, (3) neither CME nor IRF.Visual acuity (VA) and total central retinal thickness (CRT) on OCT at baseline, year 1, and year 2.Among 1131 participants with images of sufficient quality for determining CME and IRF at baseline, 92 (8.1%) had CME, 766 (67.7%) had IRF without CME, and 273 (24.1%) had neither. At baseline, eyes with CME had worse mean VA (letters) than eyes with IRF without CME and eyes with neither CME nor IRF (52 vs. 60 vs. 66 letters, P0.001); higher mean total CRT (μm) on OCT (514 vs. 472 vs. 404, P0.001); and greater hemorrhage, retinal angiomatous proliferation (RAP) lesions, and classic choroidal neovascularization (CNV). All groups showed improvement in VA at follow-up; however, the CME group started and ended with the worst VA among the 3 groups. Central retinal thickness, although higher at baseline for the CME group, was similar at 1 and 2 years follow-up for all groups. More eyes with CME (65.3%) developed scarring during 2 years of follow-up compared with eyes with IRF without CME (43.8%) and eyes with neither CME nor IRF (32.5%; P0.001).In CATT, eyes with CME had worse baseline and follow-up VA, although all groups showed similar rates of improvement in VA during 2 years of follow-up. Cystoid macular edema seems to be a marker for poorer visual outcomes in nAMD because of underlying baseline retinal dysfunction and subsequent scarring.

To compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs.Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Patients with NVAMD.Reading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra-retinal leakage of fluorescein in combination with other associated features.Visual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years.Retinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P0.001) on OCT, no leakage on FA (61% vs. 50%; P = 0.03), and greater reduction in foveal thickness (-240 μm vs. -161 μm; P0.001). They were more likely to demonstrate GA (24% vs. 15%; P = 0.01) and less likely to have scarring (17% vs. 36%; P0.001) or SHRM (36% vs. 48%; P = 0.01). These results were similar at 2 years. The mean change in lesion size at 1 year differed (-0.27 DA vs. 0.27 DA; P = 0.02), but was similar at 2 years (0.49 DA vs. 0.79 DA; P = 0.26). Among eyes treated PRN, eyes with RAP received a lower mean number of injections in year 1 (6.1 vs. 7.4; P = 0.003) and year 2 (5.4 vs. 6.6; P = 0.025).At both 1 and 2 years after initiation of anti-VEGF treatment in CATT, eyes with RAP were less likely to have fluid, FA leakage, scar, and SHRM and more likely to have GA than eyes without RAP. Mean improvement in VA was similar at 2 years.

Purpose To evaluate the association between use of antiplatelet or anticoagulant drugs and retinal or subretinal hemorrhage in participants with neovascular age-related macular degeneration (AMD) in the Comparison of AMD Treatments Trials (CATT). Design Cohort study within CATT. Participants Participants in CATT with untreated active neovascular AMD (n = 1185). Methods Participants were interviewed for use of antiplatelet or anticoagulant drugs. Trained readers evaluated photographs for the presence and size of retinal or subretinal hemorrhage at baseline and years 1 and 2. Associations between use of antiplatelet or anticoagulant drugs and hemorrhage were evaluated among all participants and by baseline hypertension status using multivariate logistic regression models. Main Outcome Measures Odds ratio for association with antiplatelet or anticoagulant use. Results Among 1165 participants with gradable photographs, 724 (62.1%) had retinal or subretinal hemorrhage at baseline; 84.4% of hemorrhages were 1 disc area (DA) or less, 8.1% were 1 to 2 DA, and 7.5% were more than 2 DA. At baseline, 608 participants (52.2%) used antiplatelet or anticoagulant drugs, including 514 participants (44.1%) using antiplatelets only, 77 (6.6%) using anticoagulants only, and 17 (1.5%) using both. Hemorrhage was present in 64.5% of antiplatelet or anticoagulant users and in 59.6% of nonusers ( P = 0.09; adjusted odds ratio [OR], 1.18; 95% confidence interval, 0.91–1.51; P = 0.21). Neither presence nor size of baseline hemorrhage was associated with the type, dose, or duration of antiplatelet or anticoagulant use. Forty-four of 1078 participants (4.08%) had retinal or subretinal hemorrhage detected on 1- or 2-year photographs; these hemorrhages were not associated with antiplatelet or anticoagulant use at baseline ( P = 0.28) or during follow-up ( P = 0.64). Among participants with hypertension (n = 807), antiplatelet or anticoagulant use was associated with a higher rate of hemorrhage at baseline (66.8% vs. 56.4%; adjusted OR, 1.48; P = 0.01), but not size of retinal or subretinal hemorrhage ( P = 0.41). Conclusions Most retinal or subretinal hemorrhages in eyes enrolled in CATT were less than 1 DA. Among all CATT participants, antiplatelet or anticoagulant use was not associated significantly with hemorrhage, but it was associated significantly with hemorrhage in participants with hypertension.

Importance Identifying the characteristics of eyes with neovascular age-related macular degeneration (nAMD) that maintain good vision without anti–vascular endothelial growth factor treatment for at least 3 years after management, as occurred in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), may have prognostic importance and help in understanding the disease and its treatment. Objectives To ascertain the characteristics of eyes in the CATT that retained good vision despite receiving no therapy for 3 years after release from the 2-year CATT treatment protocol. Design, Setting and Participants This case-control study analyzed the baseline and follow-up characteristics of eyes with nAMD that were enrolled in the CATT from 43 US clinical centers between February 20, 2008, and December 9, 2009. After initial randomization to 1 of 4 treatment groups (ranibizumab monthly, bevacizumab monthly, ranibizumab as needed, or bevacizumab as needed), at year 1, participants in the monthly groups were rerandomized to continue monthly treatment or to switch to as-needed treatment using the same drug as originally assigned. At year 2, participants were released from the protocol to treatment at the discretion of their ophthalmologist. At year 5, participants were recalled for examination. This present analysis, conducted from December 1, 2018, to September 30, 2019, compared the eyes of 40 participants (referred to as the cessation of treatment with good visual acuity, or CTGVA, group) with the eyes of the remainder of the CATT Follow-up Study (referred to as the other group). Main Outcomes and Measures Visual acuity, morphologic characteristics, and number of treatments over 5 years. Results Among 625 eyes with nAMD at baseline and a visual acuity measurement at year 5, 40 (6.4%; 95% CI, 4.7%-8.7%) were included in the analysis. These 40 participants, compared with the other group (n = 585), had a lower mean (SD) age of 74.7 (7.3) years (vs 77.7 [7.3] years;P = .01) and included 26 women (65.0%). Baseline characteristics were similar between eyes in the CTGVA and other groups, except for better visual acuity letter score in the study eye (68.8 vs 61.8;P = .001) and the fellow eye (78.4 vs 68.0;P = .01) as well as the presence of blocked fluorescence seen more often in participants in the CTGVA vs the other group (27.5% vs 13.8%;P = .02). Eyes in the CTGVA group with as-needed treatment received fewer mean (SD) injections in year 1 (5.8 [4.0] vs 8.1 [3.5]) and year 2 (7.7 [5.7] vs 13.8 [6.8]) than eyes in the other as-needed group. Mean (SD) visual acuity letter score at 5 years was 79.0 (5.5; Snellen 20/25) in the CTGVA group and 57.5 (24.2; Snellen 20/80) in the other group. Conclusions and Relevance These findings suggest that a small proportion of eyes with nAMD can retain good visual acuity with no treatment for at least 3 years after the initial 2 years of treatment. Unique characteristics of eyes that could discontinue treatment while maintaining good visual acuity could not be identified at baseline, but data suggest that not all eyes with this disease may need treatment forever. Trial Registration ClinicalTrials.gov Identifier:NCT00593450

PURPOSE: Macular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration (AMD) and are associated with poor visual acuity. We sought to identify the distribution of spectral domain optical coherence tomography (SDOCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after two years of treatment in the Comparison of AMD Treatments Trials (CATT). DESIGN: Cross-sectional analysis PARTICIPANTS: CATT participants with SDOCT, color photograph and fluorescein angiogram (CP/FA) images at Year 2. METHODS: Sixty-eight study eyes at Year 2 in CATT, were selected based on image quality and CP/FA-determined predominant presence of: geographic atrophy (GA, n=25), non-GA (NGA, n=44), fibrotic scar (FS, n=26) or non-FS (NFS, n=7). CP/FA components were delineated by CP/FA readers; SDOCT morphologic features and thicknesses were delineated by OCT readers. Using custom software and graphic user interfaces, images were registered, overlaying features and components per pixel; differences were analyzed across groups. MAIN OUTCOME MEASURES: OCT features, CP/FA components, and retinal and subretinal lesion thicknesses at each pixel of regional overlays. RESULTS: SDOCT assessment of registered areas of pathology revealed the following: 1) retinal pigment epithelium atrophy (with or without residual lesion material) covered 75% of pixels designated as GA, 22% as NGA, 24% of NFS and 46% of FS (p

OBJECTIVE: To evaluate associations of morphologic features with 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT). DESIGN: Cohort study within a randomized clinical trial. PARTICIPANTS: Participants in CATT. METHODS: Eyes with AMD-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists’ discretion thereafter. MAIN OUTCOME MEASURES: VA; thickness and morphological features on optical coherence tomography; lesion size and foveal composition on fundus photography and fluorescein angiography. RESULTS: VA and image gradings were available for 523 of 914 (57%) participants alive at 5 years. At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid (SRF), 36% had sub-retinal pigment epithelium (RPE) fluid, and 66% had subretinal hyper-reflective material (SHRM). Mean (SD) foveal center thickness (μm) was 148 (99) for retina, 5 (21) for SRF, 125 (107) for subretinal tissue complex, 11 (33) for SHRM, and 103 (95) for RPE+RPE elevation. SHRM, thinner retina, greater CNV lesion area and foveal center pathology (all p

Throughout the years, DNA barcoding has gained in importance in forensic entomology as it leads to fast and reliable species determination. High-quality results, however, can only be achieved with a comprehensive DNA barcode reference database at hand. In collaboration with the Bavarian State Criminal Police Office, we have initiated at the Bavarian State Collection of Zoology the establishment of a reference library containing arthropods of potential forensic relevance to be used for DNA barcoding applications. CO1-5P' DNA barcode sequences of hundreds of arthropods were obtained via DNA extraction, PCR and Sanger Sequencing, leading to the establishment of a database containing 502 high-quality sequences which provide coverage for 88 arthropod species. Furthermore, we demonstrate an application example of this library using it as a backbone to a high throughput sequencing analysis of arthropod bulk samples collected from human corpses, which enabled the identification of 31 different arthropod Barcode Index Numbers.

Speaking to a need for innovative methods in data collection, this study demonstrates the utilization of web-based, automated SMS text messages in survey research in an attempt to cost-effectively reach more diverse samples of citizens, through their cell phones. The Textizen™ web-based SMS text message platform allows for the large-scale administration of short, text-based surveys. Of particular interest to survey researchers, some traditionally harder-to-reach populations, such as low-income and minority populations, have been quick to adopt mobile phone technologies, and use text-messaging services a higher rate than others. This study describes a recent test of SMS text messages as a “primary” mode of data collection – both in recruiting participants, and administering a survey in a regional context. A sample of 1,000 mobile subscribers was contacted via a “cold text” asking them to participate in a 5-question survey regarding their opinion on a local park; a raffle of 10 iPads was offered as incentive. Non-respondents received follow-up phone calls to determine their reason(s) for not responding, such as a non-working number, the inability to receive text messages, non-interest in text-message survey participation, or invasion of privacy. Significant empirical results include the rate of text message non-receipt, rate of text message receipt, frequency of reported barriers to responding (reasons for not responding), and demographics of respondents. Findings provide rich insight into the use for automated text messages in survey research in general, and have implications for particular local and global markets where the number of mobile subscribers and text message usage is high. This study can inform future experiments aimed to increase both response rates and cost effectiveness, as well as access traditionally harder to reach populations.

Die WOLVES (Wolfsburg HPV Epidemiology Study)-Studie ist die erste populationsbasierte Langzeitbeobachtungsstudie in Deutschland zu HPV-assoziierten Erkrankungen in einem Normalkollektiv. Alle Frauen der Geburtsjahrgange 1983/84 und 1988/89, die beim Einwohnermeldeamt mit erstem Wohnsitz in Wolfsburg gemeldet waren, wurden zur Teilnahme eingeladen. Die Teilnehmerinnen beantworteten einen Fragebogen zu Vorerkrankungen, Sexualleben, sexuell ubertragbaren Infektionen (STI) sowie Bildung und Sozialstatus. Es erfolgten eine gynakologische Vorsorgeuntersuchung mit zytologischem Abstrich, HPV-Test und HPV-Genotypisierung. Bei Genitalwarzen oder auffalligen Abstrichen erfolgte eine Differenzialkolposkopie. Insgesamt wurden bis 12/2014 1.672 Frauen eingeschlossen, das entspricht 44 % der Jahrgange 1983/84 und 75 % der Jahrgange 1988/89. Die HPV-Gesamtpravalenz lag bei 25,9 %, ohne signifikante Unterschiede zwischen den Gruppen. Die Anzahl der Sexualpartner korrelierte signifikant mit der Wahrscheinlichkeit einer HPV-Infektion. Bei 0,9 % wurden Genitalwarzen diagnostiziert, fur 1983/84 Geborene lag das Risiko bis zum 27. Geburtstag bei 4,8 %. Bei 2,51 % aller Teilnehmerinnen wurden CIN2+ histologisch gesichert. HPV 16 zeigte die hochste Pravalenz (7,1 %) aller high-risk HPV-Typen, HPV 6 war der wichtigste low-risk HPV-Typ (1,8 %). HPV-Infektionen sind in Deutschland bei jungen Frauen sehr haufig, die Last HPV-assoziierter Erkrankungen ist relevant, andere STI spielen eine vergleichsweise geringere Rolle.

Although recent work has begun to identify factors associated with risk of treatment attrition for juvenile offenders, few of these studies have considered how community context is related to the completion of juvenile offender treatment. The current work examines the relationship between social distance and treatment attrition for juvenile offenders. Analyzing a data set of 5,517 juvenile offenders adjudicated in Philadelphia, the results of cross-classified hierarchical models indicate that social distance, operationalized in two ways that consider perceptions of both the ethnic composition and level of disadvantage within neighborhoods, does not directly predict the likelihood of treatment attrition. However, when considered with the ethnicity of the juvenile offenders in the form of an interaction effect, social distance based on perceptions of ethnicity within neighborhoods is shown to predict the likelihood of treatment attrition, and to be more acute for young non-White offenders. The implications of these findings are discussed.

Purpose To describe risk factors for scar formation and changes to fibrotic scar through 5 years in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Multicenter, prospective cohort study. Participants A total of 1061 subjects in CATT. Methods Color photographic and fluorescein angiographic images from baseline and 1, 2, and 5 years were evaluated. Incidence of scar formation was estimated with Kaplan–Meier curves. Risk factors were assessed with Cox regression models. Main Outcome Measures Scar formation, fibrotic scar area, and macular atrophy associated with fibrotic scar ("atrophy"). Results Cumulative proportion of eyes with scar was 32%, 46%, and 56% at years 1, 2, and 5, respectively. Baseline factors associated with increased risk (adjusted hazards ratio [aHR] and 95% confidence interval [CI]) were classic choroidal neovascularization (CNV) (aHR, 4.49; 95% CI, 3.34–6.04) versus occult, hemorrhage >1 disc area (DA) (aHR, 2.28; 95% CI, 1.49–3.47) versus no hemorrhage, retinal thickness >212 μm (aHR, 2.58; 95% CI, 1.69–3.94) versus 275 μm (aHR, 2.64; 95% CI, 1.81–3.84) versus ≤75 μm, subretinal fluid thickness >25 μm (aHR, 1.31; 95% CI, 0.97–1.75) versus no fluid, visual acuity (VA) in fellow eye 20/20 (aHR, 1.72; 95% CI, 1.25–2.36) versus 20/50 or worse, retinal pigment epithelium elevation absence (aHR, 1.71; 95% CI, 1.21–2.41), and subretinal hyperreflective material (aHR, 1.72; 95% CI, 1.25–2.36). Among 68 eyes that developed fibrotic scar at year 1, VA decreased by a mean of additional 13 letters between years 1 and 5. Mean scar area was 1.2, 1.2, and 1.9 DA at 1, 2, and 5 years, respectively. Atrophy was present in 18%, 24%, and 54% of these eyes at years 1, 2, and 5, respectively; the mean areas were 1.6, 2.0, and 3.1 DA, respectively. Atrophy replaced fibrotic scar in 8 eyes at year 5. There was no significant correlation between scar growth and atrophy growth. The rate of growth for both was similar between the clinical trial and observation periods. Conclusions Several morphologic features, including classic CNV and large hemorrhage, are associated with scar formation. Rate of new scar formation declined after 2 years. Most fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.

Introduction: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and predicts the risk of cardiovascular disease (CVD). Risk factors for the progression of CAC in patients with CKD have not been well studied. Hypothesis: We assessed the hypothesis that several established and novel CVD risk factors are associated with progression of CAC among patients with CKD. Methods: In a random subsample of 1,123 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured at baseline and the follow-up visit using electron beam computed tomography (CT) or multidetector CT. CAC progression was defined as an increase of Agatston score ≥100 units during follow-up. Multiple logistic regression and mixed-effects regression models were used to assess risk factors for progression of CAC. Results: Over an average of 3-year follow-up, 332 (29.6%) participants developed CAC progression. After adjusting for age, sex, race, clinical site, total cholesterol, HDL-cholesterol, systolic blood pressure, antihypertensive treatment, diabetes, and current smoking in the multivariable models, history of CVD (odds ratio [OR] 1.53, 95% CI 1.09-2.15, p=0.02), lipid-lowering treatment (OR 1.81, 95% CI 1.28-2.55, p Conclusions: In conclusion, these data suggest that reduced kidney function, calcium and phosphate metabolic disorders and inflammation, in addition to established CVD risk factors, might play a role in CAC progression among patients with CKD.

Purpose To develop methods to make precise comparisons of specific retinal features between and within spectral-domain (SD) OCT images, color fundus photography (CFP) images, and fluorescein angiography (FA) images in eyes treated with anti–vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD). Design Retrospective study. Participants Patients with good study-eye images at the 104-week visit in the Comparison of Age-Related Macular Degeneration Treatments Trials. Methods Graders reviewed CFP and FA images and delineated areas of fibrotic or nonfibrotic scar and geographic atrophy (GA) or non-GA. Other graders reviewed SD-OCT images and delineated retinal and subretinal lesion characteristics. Using newly developed custom software and graphic user interfaces, the presence and thickness of each feature at each pixel on the en face view was determined. Main Outcome Measures Spectral-domain OCT findings versus CFP and FA lesion components from regional overlays. Results Per-eye distribution and thickness of SD-OCT features within CFP- and FA-established areas of scar and atrophy can be determined precisely, can be displayed in multiple formats, and can be extracted into pixel-specific data sets. These methods enable statistical analysis of imaging results within eyes and across eyes of different patients. For example, photoreceptor loss, subretinal lesion material, and thicknesses of photoreceptor layer and subretinal material across those SD-OCT features can be related precisely to CFP and FA regions of scar or atrophy. Conclusions Methods to integrate qualitative and quantitative retinal and subretinal changes to coincide with photographic and angiographic designations of the nAMD lesion areas and sequelae are integral for accurate assessments of posttreatment retinal morphologic features. These may lead to better understanding of disease progression and improved treatment strategies.

To compare baseline characteristics, visual acuity (VA) and morphological outcomes between eyes with baseline hard exudates (HE) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factors (anti-VEGF).Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Patients with NVAMD.Readers evaluated baseline and follow-up morphology on digital color images, fluorescein angiography (FA), and optical coherence tomography (OCT) in eyes with NVAMD that were randomly assigned to treatment with either ranibizumab or bevacizumab. Ophthalmologists identified HE on color images in the study eye.VA; scar; geographic atrophy; retinal thickness, fluid; and number of anti-VEGF injections.HE was present in 128 of 1185 (11%) study eyes at baseline, 77% within 1 disc diameter of the foveal center. Patients with study eye HE were more likely female (81% vs 60%; p0.001) and non-smokers (53% vs 42%; p=0.004). Both groups had similar proportions of hypercholesterolemia and hypertriglyceridemia. At baseline, eyes with HE had worse VA (mean 57 vs 61 letters; p=0.003), larger total lesion size (3.3 vs 2.4 DA; p0.001), greater total foveal thickness (522µm vs 452µm; p0.001), more retinal angiomatous proliferation (18% vs 10%; p=0.009) and sub-RPE fluid (65% vs 47%; p0.001). At 1 year, VA was similar in both groups; more eyes with baseline HE had no fluid (45% vs 29%; p0.001) and greater reduction in total foveal thickness (-266µm vs -158u; p0.001). VA at year 2 was similar but retinas of eyes with baseline HE were thinner (267µm vs 299µm; p=0.03) and fewer eyes had sub-retinal fluid (23% vs 36%; p=0.008). HE was present in 19% of eyes at 1 year and 5% of eyes at 2 years. LIPC promoter SNP rs10468017 was not associated with NVAMD HE.Eyes with HE have larger CNV lesions and more RAP. Their initially thicker retina rapidly becomes thinner on anti-VEGF treatment. HE is not significantly associated with hyperlipidemia. HE at baseline does not significantly influence VA, scar and GA outcomes in eyes with NVAMD treated with anti-VEGF. Few eyes have HE at year 2.

Retinal abnormalities may be associated with changes in the renal vasculature. This study assessed the association between retinopathy and progression of kidney disease in participants of the Chronic Renal Insufficiency Cohort (CRIC) study.This was a prospective study in which patients with CKD enrolled in CRIC had nonmydriatic fundus photographs of both eyes. All CRIC participants in six clinical sites in which fundus cameras were deployed were offered participation. Photographs were reviewed at a reading center. The presence and severity of retinopathy and vessel calibers were assessed using standard protocols by graders masked to clinical information. The associations of retinal features with changes in eGFR and the need for RRT (ESRD) were assessed.Retinal images and renal progression outcomes were obtained from 1852 of the 2605 participants (71.1%) approached. During follow-up (median 2.3 years), 152 participants (8.2%) developed ESRD. Presence and severity of retinopathy at baseline were strongly associated with the risk of subsequent progression to ESRD and reductions in eGFR in unadjusted analyses. For example, participants with retinopathy were 4.4 times (95% confidence interval [95% CI], 3.12 to 6.31) more likely to develop ESRD than those without retinopathy (P0.001). However, this association was not statistically significant after adjustment for initial eGFR and 24-hour proteinuria. Venular and arteriolar diameter calibers were not associated with ESRD or eGFR decline. The results showed a nonlinear relationship between mean ratio of arteriole/vein calibers and the risk of progression to ESRD; participants within the fourth arteriole/vein ratio quartile were 3.11 times (95% CI, 1.51 to 6.40) more likely to develop ESRD than those in the first quartile (P0.001).The presence and severity of retinopathy were not associated with ESRD and decline in eGFR after taking into account established risk factors.

An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44±15 ml/min per 1.73 m(2)). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR], 1.45 per doubling [95% confidence interval (CI), 1.28 to 1.65]; HR for highest versus lowest quartile, 2.98 [95% CI, 1.97 to 4.52]) and atherosclerotic events (HR per doubling, 1.24 [95% CI, 1.09 to 1.40]; HR for highest versus lowest quartile, 1.76 [95% CI, 1.20 to 2.59]). Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.

Purpose To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Cohort within a randomized clinical trial. Participants We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. Methods Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). Main Outcome Measures Development of GA. Results By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43–4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16–2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40–3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34–3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29–0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35–0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19–0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31–0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06–1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17–2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH , ARMS 2 , HTRA1 , C3 , or TLR3 . Conclusions Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.