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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.

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

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 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.

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.

To describe outcomes 5 years after initiating treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD).Cohort study.Patients enrolled in the Comparison of AMD Treatments Trials.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.Visual acuity (VA) and morphologic retinal features.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 (120 μm) in 36% of eyes. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (-4 letters; P = 0.008). Otherwise, there were no statistically significant differences in VA or morphologic outcomes between drug or regimen groups.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 describe the association between morphologic features on fundus photography (FP), fluorescein angiography (FA), and optical coherence tomography (OCT) and visual acuity (VA) in the second year of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Prospective cohort study within a randomized clinical trial. Participants Participants in the CATT. Methods Study eye eligibility required angiographic and OCT evidence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and VA between 20/25 and 20/320. Treatment was assigned randomly to ranibizumab or bevacizumab with 3 different dosing regimens over a 2-year period. Main Outcome Measures Fluid type, location, and thickness; retina and subretinal tissue complex thickness on OCT; size and lesion composition on FP and FA; and VA. Results Among 1185 CATT participants, 993 (84%) had fluid on OCT at baseline and completed 2 years of follow-up. At 2 years, intraretinal fluid (IRF), subretinal fluid (SRF), sub–retinal pigment epithelium (RPE) fluid, and subretinal tissue complex thickness decreased in all treatment groups. Ranibizumab monthly was best able to resolve each type of fluid. Eyes with SRF in the foveal center on OCT had better mean VA than eyes with no SRF (72.8 vs. 66.6 letters; P = 0.006). Eyes with IRF in the foveal center had worse mean VA than eyes without IRF (59.9 vs. 70.9 letters; P 212 μm (59.4 vs. 71.3 vs. 70.3 letters; P P Conclusions The associations between VA and morphologic features identified through year 1 were maintained or strengthened during year 2. Eyes with foveal IRF, abnormally thin retina, greater thickness of the subretinal tissue complex on OCT, and subfoveal geographic atrophy or scar on FP/FA had the worst VA. Subretinal fluid was associated with better VA.

Patients with chronic kidney disease (CKD) experience other diseases such as cardiovascular disease (CVD) and retinopathy. The purpose of this study was to assess whether retinopathy predicts future CVD events in a subgroup of the participants of the Chronic Renal Insufficiency Cohort (CRIC) study. In this ancillary investigation, 2,605 participants of the CRIC study were invited to participate, and nonmydriatic fundus photographs were obtained in 1,936 subjects. Using standard protocols, presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed at a central photograph reading center by trained graders masked to study participant's information. Patients with a self-reported history of cardiovascular disease were excluded. Incident CVD events were adjudicated using medical records. Kidney function measurements, traditional and nontraditional risk factors, for CVD were obtained. Presence and severity of retinopathy were associated with increased risk of development of any CVD in this population of CKD patients, and these associations persisted after adjustment for traditional risk factors for CVD. We also found a direct relation between increased venular diameter and risk of development of CVD; however, the relation was not statistically significant after adjustment for traditional risk factors. In conclusion, the presence of retinopathy was associated with future CVD events, suggesting that retinovascular pathology may be indicative of macrovascular disease even after adjustment for renal dysfunction and traditional CVD risk factors. Assessment of retinal morphology may be valuable in assessing risk of CVD in patients with CKD, both clinically and in research settings.

Importance Although anti–vascular endothelial growth factor treatment of neovascular age-related macular degeneration (AMD) results in improved vision overall, loss of substantial vision can occur. Understanding the processes that lead to loss of vision may lead to preventive strategies. Objective To determine the incidence, characteristics, causes, and baseline predictors of sustained visual acuity loss after 2 years of treatment with ranibizumab or bevacizumab for neovascular AMD. Design, Setting, and Participants A cohort study within a randomized clinical trial of participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Interventions Participants were randomly assigned to treatment with ranibizumab or bevacizumab and to 2 years of monthly or as needed injections or monthly injections for 1 year and as needed injections the following year. Main Outcomes and Measures Sustained visual acuity loss, defined as loss of 15 or more letters from baseline at weeks 88 and 104. Results Among 1030 participants, 61 eyes (5.9%) developed sustained visual acuity loss in 2 years. Within this group, visual acuity decreased gradually over time, with a mean decrease of 2, 19, and 33 letters from baseline at 4 weeks, 1 year, and 2 years, respectively. At 2 years, eyes with sustained visual acuity loss had more scarring (60.0% vs 41.4%, P = .007), more geographic atrophy (GA) (31.6% vs 20.7%, P = .004), larger lesions (16 vs 8 mm 2 , P P P P P P = .006), larger area of choroidal neovascularization (OR for a >4-disc area vs ≤1-disc area, 3.91; 95% CI, 1.70-9.03; P = .007), and bevacizumab treatment (OR, 1.83; 95% CI, 1.07-3.14; P = .03). Conclusions and Relevance Sustained visual acuity loss was relatively rare in CATT. The development of foveal scar, pigmentary abnormalities, or GA contributed to most of the sustained visual acuity loss. Risk was 3% higher among eyes treated with bevacizumab. Treatment that targeted the prevention of scarring or GA may improve vision outcomes. Trial Registration clinicaltrials.gov Identifier:NCT00593450

To determine the relationship between delayed patchy choroidal filling and morphologic and functional outcomes among eyes treated with ranibizumab or bevacizumab.Cohort study.Comparison of Age-related Macular Degeneration Treatment Trials participants were assigned randomly to ranibizumab or bevacizumab on a monthly or as-needed schedule. Presence of delayed patchy choroidal filling and morphologic and functional outcomes were evaluated among eyes with gradable fluorescein angiography at baseline (n = 973) and at 1 year (n = 860) eyes.Delayed filling was present in 75 (7.7%) of 973 eyes at baseline. Eyes with incident delayed filling at 1 year (23 [2.9%] of 798) showed a mean decrease of 1.7 letters in visual acuity, whereas eyes without incident delayed filling had a mean improvement of 8.1 letters (difference [Δ], -9.8; 95% confidence interval [CI] , -15.8 to -3.9; P.01). Eyes with incident delayed filling had a larger increase in mean total lesion area of choroidal neovascularization (3.00 mm(2)) than eyes without incident delayed filling (0.56 mm(2); Δ , 2.4; 95% CI, 0.4 to 4.4; P = .02). The proportion with incident delayed filling at 1 year was similar among eyes treated with ranibizumab (10 [2.4%] of 413) or bevacizumab (13 [3.3%] of 385; P = .53) and among eyes treated monthly (12 [3.1%] of 388) or as needed (11 [2.7%] of 410; P = .83).Delayed patchy choroidal filling was uncommon at baseline. Although only a small percentage of eyes demonstrated delayed filling during the first year of anti-vascular endothelial growth factor treatment, these eyes had worse visual acuity and a larger increase in total lesion area of choroidal neovascularization.

Objective To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Design Cohort study of patients enrolled in a multicenter, randomized clinical trial. Participants Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Methods Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. Main Outcome Measures Development of CNV in the fellow eye. Results Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], –1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8–1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 ( CFH ), rs10490924 ( ARMS2 ), rs11200638 ( HTRA1 ), and rs2230199 ( C3 ; P >0.35). Conclusions Through 2 years, there was no statistically significant difference between ranibizumab and bevacizumab in incidence of CNV in the fellow eye. Genotype on 4 SNPs previously found to be associated with AMD did not affect the risk of CNV in the fellow eye among CATT patients. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The present article describes a standard instrument for the continuous online determination of retinal vessel diameters, the commercially available retinal vessel analyzer. This report is intended to provide informed guidelines for measuring ocular blood flow with this system. The report describes the principles underlying the method and the instruments currently available, and discusses clinical protocol and the specific parameters measured by the system. Unresolved questions and the possible limitations of the technique are also discussed.

Regulated delivery and removal of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) from postsynaptic elements has been proposed as a mechanism for regulating synaptic strength. Here we test the role of ubiquitin in regulating synapses that contain a C. elegans GluR, GLR-1. GLR-1 receptors were ubiquitinated in vivo. Mutations that decreased ubiquitination of GLR-1 increased the abundance of GLR-1 at synapses and altered locomotion behavior in a manner that is consistent with increased synaptic strength. By contrast, overexpression of ubiquitin decreased the abundance of GLR-1 at synapses and decreased the density of GLR-1-containing synapses, and these effects were prevented by mutations in the unc-11 gene, which encodes a clathrin adaptin protein (AP180). These results suggest that ubiquitination of GLR-1 receptors regulates synaptic strength and the formation or stability of GLR-1-containing synapses.