Postnatal Serum Insulin-Like Growth Factor I and Retinopathy of Prematurity in Latin American Infants.

PURPOSE: Identifying at-risk infants for retinopathy of prematurity (ROP) is complex in countries with emerging economies as infants that lack conventional risk factors, such as low birth weight (BW) and young gestational age (GA), still go on to develop severe ROP. Potential biomarkers, like serum insulin-like growth factor 1 (IGF-1) and slow postnatal weight gain, have been identified as good predictors for ROP in developed countries. We sought to determine the relationship between IGF-1 levels and ROP in two Latin American countries where the burden of disease is still significant. METHODS: Prospective cohort study of infants in Guadalajara, Mexico and La Plata, Argentina. Filter-paper bloodspot IGF-1 assays were performed weekly from birth until hospital discharge or 40 weeks' postmenstrual age (PMA). RESULTS: 112 infants were studied with a median BW of 1412 g (range 620 g-2390 g) and a median GA of 33 weeks (range 25-37). There was no significant difference in IGF-1 between infants who developed ROP and those who did not. CONCLUSION: Low IGF-1 was not associated with ROP in these infants. The lack of an association between ROP and IGF-1 in Latin America supports the observation that growth-based predictive models do not perform as well in this setting where more mature babies still develop severe ROP.

COMBINING INFORMATION FROM MULTIPLE DATA SOURCES TO ASSESS POPULATION HEALTH.

Information about an extensive set of health conditions on a well-defined sample of subjects is essential for assessing population health, gauging the impact of various policies, modeling costs, and studying health disparities. Unfortunately, there is no single data source that provides accurate information about health conditions. We combine information from several administrative and survey data sets to obtain model-based dummy variables for 107 health conditions (diseases, preventive measures, and screening for diseases) for elderly (age 65 and older) subjects in the Medicare Current Beneficiary Survey (MCBS) over the fourteen-year period, 1999-2012. The MCBS has prevalence of diseases assessed based on Medicare claims and provides detailed information on all health conditions but is prone to underestimation bias. The National Health and Nutrition Examination Survey (NHANES), on the other hand, collects self-reports and physical/laboratory measures only for a subset of the 107 health conditions. Neither source provides complete information, but we use them together to derive model-based corrected dummy variables in MCBS for the full range of existing health conditions using a missing data and measurement error model framework. We create multiply imputed dummy variables and use them to construct the prevalence rate and trend estimates. The broader goal, however, is to use these corrected or modeled dummy variables for a multitude of policy analysis, cost modeling, and analysis of other relationships either using them as predictors or as outcome variables.

Refractive change in children with accommodative esotropia.

OBJECTIVE: To determine whether there is a measurable change in hyperopia in children with accommodative esotropia over time. METHODS AND ANALYSIS: A retrospective cohort of children with fully or partially accommodative esotropia diagnosed by age 7 years, followed to age 10 or older, and with at least two cycloplegic refractions, one before age 7 years and one after age 10 years. The annual change was calculated from linear mixed-effect models, overall and during two age periods with subgroup analysis by baseline refractive error (<4D, ≥4D) and type (partial, full) of accommodative esotropia. RESULTS: 405 subjects were studied. Mean age at first and last visit was 3.2 and 12.1 years, respectively, with mean 7.6 cycloplegic refractions. The annual change (95% CI) in refractive error was -0.071 (-0.087 to -0.055) D/yr. Between ages 3 and 7, hyperopia among children with baseline hyperopia <4D increased by 0.12 (0.08 to 0.16) D/yr, while hyperopia among those with baseline 4D or greater was stable (0.0D/yr, -0.03 to 0.04) (p<0.001). Hyperopia decreased from age 7 to 15 years in both subgroups: <4D subgroup -0.17 (-0.20 to -0.14) D/yr, ≥4D subgroup -0.18 (-0.21 to -0.15) D/yr (p=0.58). There was no significant difference in refractive change between fully (n=274) and partially (n=131) accommodative esotropia (p≥0.10). CONCLUSION: Hyperopia in children with accommodative esotropia is stable or increases up to age 7 years, depending on baseline hyperopia, but decreases gradually between ages 7 and 15 years regardless of baseline refractive error.

Altered ocular parameters from circadian clock gene disruptions.

The pathophysiology of refractive errors is poorly understood. Myopia (nearsightedness) in particular both blurs vision and predisposes the eye to many blinding diseases during adulthood. Based on past findings of diurnal variations in the dimensions of the eyes of humans and other vertebrates, altered diurnal rhythms of these ocular dimensions with experimentally induced myopia, and evolving evidence that ambient light exposures influence refractive development, we assessed whether disturbances in circadian signals might alter the refractive development of the eye. In mice, retinal-specific knockout of the clock gene Bmal1 induces myopia and elongates the vitreous chamber, the optical compartment separating the lens and the retina. These alterations simulate common ocular findings in clinical myopia. In Drosophila melanogaster, knockouts of the clock genes cycle or period lengthen the pseudocone, the optical component of the ommatidium that separates the facet lens from the photoreceptors. Disrupting circadian signaling thus alters optical development of the eye in widely separated species. We propose that mechanisms of myopia include circadian dysregulation, a frequent occurrence in modern societies where myopia also is both highly prevalent and increasing at alarming rates. Addressing circadian dysregulation may improve understanding of the pathogenesis of refractive errors and introduce novel therapeutic approaches to ameliorate myopia development in children.

Effective Three-Body Interactions in Cs(6s)-Cs(nd) Rydberg Trimers.

Ultralong-range Rydberg trimer molecules are spectroscopically observed in an ultracold gas of Cs(nd_{3/2}) atoms. The anisotropy of the atomic Rydberg state allows for the formation of angular trimers, whose energies may not be obtained from integer multiples of dimer energies. These nonadditive trimers coexist with Rydberg dimers. The existence of such effective three-body interactions is confirmed with the observation of asymmetric line profiles and interpreted by a theoretical approach that includes relativistic spin interactions. Simulations of the observed spectra with and without angular trimer lines lend convincing support to the existence of effective three-body interactions.

Causes and Consequences of Phenotypic Plasticity in Complex Environments.

Phenotypic plasticity is a ubiquitous and necessary adaptation of organisms to variable environments, but most environments have multiple dimensions that vary. Many studies have documented plasticity of a trait with respect to variation in multiple environmental factors. Such multidimensional phenotypic plasticity (MDPP) exists at all levels of organismal organization, from the whole organism to within cells. This complexity in plasticity cannot be explained solely by scaling up ideas from models of unidimensional plasticity. MDPP generates new questions about the mechanism and function of plasticity and its role in speciation and population persistence. Here we review empirical and theoretical approaches to plasticity in response to multidimensional environments and we outline new opportunities along with some difficulties facing future research.

Prevalence and Onset of Pediatric Sickle Cell Retinopathy.

PURPOSE: Children with sickle cell hemoglobinopathy (SCH) can demonstrate proliferative retinopathy with vision loss, but lack of consensus exists regarding screening regimens. We sought to determine the prevalence, age at onset, and risk factors associated with sickle cell retinopathy (SCR) to inform development of screening guidelines for asymptomatic children. DESIGN: Retrospective cohort study. PARTICIPANTS: Children with SCH over a 4-year period. METHODS: Prevalences of any retinopathy, nonproliferative retinopathy (NPR), and proliferative retinopathy (PR), determined as proportions of all children examined, were calculated. Subgroup analyses were completed by SCH genotype. Ages at first diagnosis were reported using standard descriptive statistics. The association of potential risk factors with retinopathy were assessed using univariate and multivariate linear and logistic regression. MAIN OUTCOME MEASURES: Outcomes were prevalence, age at onset, and type of SCR, based on examination by an ophthalmologist. Markers of SCH severity (number of emergency room or hospital admissions for crises, number of blood transfusions, hydroxyurea therapy, transcranial Doppler-confirmed cerebral vasculopathy), genotype, gender, and race were evaluated as SCR risk factors. RESULTS: Of 398 children (mean age, 9.6±4.6 years; range 0-18 years), 208 (52%) showed sickle cell homozygote (SS) genotype, 113 (28%) showed sickle cell hemoglobin C (SC) genotype, and 77 (19%) showed trait genotype. Forty-eight children (12.1%) demonstrated SCR, 44 of 398 children (11.1%; 95% confidence interval, 8.3%-14.5%) demonstrated NPR, and 9 of 398 children (2.3%; 95% confidence interval, 1.2%-4.2%) demonstrated PR. Prevalence was higher for SC than SS genotype for NPR (21% vs. 9%) and PR (5% vs. 1%); onset for SC genotype was earlier than that for SS genotype for NPR (youngest diagnosis 4.8 vs. 6.1 years) and PR (12.2 vs. 15.4 years). No other risk factors were associated significantly with SCR. CONCLUSIONS: Clinical markers of SCH severity assessed were not associated with SCR and are not necessary for screening guidelines. Based on our study and literature review, although screening could begin at age 5 years for NPR, screening of children without ophthalmologic symptoms to identify treatment-requiring PR could begin later, at 9 years of age for SC and 13 years of age for SS.

Dietary Zinc-Amino Acid Complex Does Not Affect Markers of Mammary Epithelial Integrity or Heat Stability of Milk in Mid-Lactating Cows.

Supplying dietary zinc in excess of traditional requirements has clear impacts on the gut epithelium, but little research has explored whether similar impacts on the mammary epithelium may occur. Our objective was to determine the effects of supplemental Zn sources, in excess of minimal requirements, on markers of mammary epithelial integrity in blood and in milk as well as the heat stability of milk in mid-lactation cows. Twelve multiparous Holstein cows (132 ± 21 days in milk and 51 ± 3 kg/day milk) were blocked according to milk yield and enrolled in a replicated 3 × 3 Latin square experiment. Experimental periods were 21 days, with 17 days allowed for diet adaptation and 4 days for sampling. Treatment sequences were randomly assigned to animals and treatments were as follows: (1) 0.97 g Zn/day provided as ZnSO4 (34.5 mg supplemental Zn/kg diet DM; 30-ZS), (2) 1.64 g Zn/day provided as ZnSO4 (56.5 mg supplemental Zn/kg diet DM; 60-ZS), and (3) 0.55 g Zn/day provided as ZnSO4 plus 1.13 g Zn/day provided as a zinc-methionine complex (58.2 mg supplemental Zn/kg diet DM; 60-ZM). Treatments were administered once daily as an oral bolus containing all supplemental trace minerals. Rumen-bypass methionine was also included in the 30-ZS and 60-ZS boluses to provide metabolizable methionine equivalent to that provided in 60-ZM rations. Milk samples were assessed for electrolytes, somatic cell transcript abundance of genes related to zinc metabolism, and heat coagulation time. Whole blood samples were analyzed for Na and K concentrations, and plasma samples were analyzed for lactose concentration. Cows fed 60-ZS or 60-ZM had greater zinc intake compared to 30-ZS. Dry matter intake and milk fat content tended to be greater in 60-ZS and 60-ZM cows compared to 30-ZS. Somatic cell linear score was similar among treatments. Treatments neither affected markers of mammary epithelial integrity in blood nor in milk of cows, including plasma concentration of lactose, milk concentrations of Na+ and K+, and SLC30A2 and CLU transcript abundance. Treatments had no effect on milk N fractions or heat coagulation time. This study provided no evidence that supplemental Zn above the established requirements can improve blood-milk epithelial barrier or heat stability of milk in healthy mid-lactation dairy cows.

Development of Modified Screening Criteria for Retinopathy of Prematurity: Primary Results From the Postnatal Growth and Retinopathy of Prematurity Study.

Importance: Current retinopathy of prematurity (ROP) guidelines, which are based on studies of high-risk infants and expert opinion, have low specificity for disease requiring treatment. Postnatal weight gain-based models improve specificity but have been limited by complexity and small development cohorts, which results in model overfitting and resultant decreased sensitivity in validation studies. Objective: To develop a birth weight (BW), gestational age (GA), and weight gain (WG) prediction model using data from a broad-risk cohort of premature infants. Design, Setting, and Participants: The Postnatal Growth and ROP Study was a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada from 2006 to 2012 that included 7483 premature infants at risk for ROP with a known ROP outcome. A hybrid modeling approach was used that combined BW/GA criteria, weight comparison with expected growth from infants without ROP, multiple growth-interval assessments, consideration of nonphysiological WG, and user-friendly screening criteria. Numerous BW/GA levels, postnatal age periods, time intervals, and WG percentile thresholds were evaluated to identify the most robust parameters. Main Outcome and Measures: Sensitivity for Early Treatment of ROP Study type 1 ROP and potential reduction in infants who require examinations. Results: Of 7483 infants, the median (SD) BW was 1099 (359) g, the median GA was 28 weeks (range, 22-35), 3575 (47.8%) were female, 3615 (48.4%) were white, 2310 (30.9%) were black, 233 (3.1%) were Asian, 93 (1.2%) were Pacific Islander, and 40 (0.5%) were American Indian/Alaskan Native. Infants who met any of 6 criteria would undergo examinations: (1) a GA of younger than 28 weeks; (2) a BW of less than 1051 g; a WG of less than 120 g, 180 g, or 170 g during ages 10 to 19, 20 to 29, or 30 to 39 days, respectively; or hydrocephalus. These criteria predicted 459 of 459 (100%) type 1 (sensitivity, 100%; 95% CI, 99.2%-100%), 524 of 524 (100%) treated, and 466 of 472 (98.7%) type 2 cases while reducing the number of infants who required examinations by 2269 (30.3%). Conclusions and Relevance: This cohort study, broadly representative of infants who are undergoing ROP examinations, provides evidence-based screening criteria. With validation, the Postnatal Growth and ROP Study criteria could be incorporated into ROP screening guidelines to reduce the number of infants who require examinations in North America.

Ocular complications following treatment in the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study.

PURPOSE: To determine the prevalence of treatment-related ocular complications and disease progression following treatment for retinopathy of prematurity (ROP). METHODS: This was a retrospective cohort study of eyes treated for ROP at 29 North American neonatal intensive care units in the Postnatal Growth and ROP (G-ROP) Study. Data from the time of treatment through 15 months were abstracted from medical records by certified data collectors. Treatment-related complication (cataract, hyphema, glaucoma, corneal abrasion/opacity), and disease-progression (retinal fold, dragging, or stage 4 or 5 detachment) were calculated by treatment modality. Vitreous hemorrhage was classified separately, because it can relate to treatment or disease progression. RESULTS: Of 7,483 infants included in the study, 1,004 eyes (512 infants) underwent ROP treatment: 970 eyes received laser as initial therapy; 34 eyes received intravitreal bevacizumab (IVB). Median follow-up after treatment was 18 weeks. Overall, one or more complications occurred in 2.6% (95% CI, 1.8%-3.8%) laser treated eyes and no (0%; 95% CI, 0.0%-10.1%) IVB eyes. Disease-progression occurred in 9.2% (95% CI, 7.6%-11.2%) laser treated eyes, no (0%; 95% CI, 0.0-12.9%) IVB-only eyes. Vitreous hemorrhage occurred in 5.4% (95% CI: 4.1% - 7.0%) laser treated eyes, no IVB-only eyes. CONCLUSIONS: Rates of complications are very low following ROP treatment with either laser or IVB. Of laser-treated eyes, 9% experienced disease progression despite treatment.

Visual and Morphologic Outcomes in Eyes with Hard Exudate in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: 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). DESIGN: Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). PARTICIPANTS: Patients with NVAMD. METHODS: 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. MAIN OUTCOME MEASURES: VA; scar; geographic atrophy; retinal thickness, fluid; and number of anti-VEGF injections. RESULTS: 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%; p<0.001) 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; p <0.001), greater total foveal thickness (522µm vs 452µm; p<0.001), more retinal angiomatous proliferation (18% vs 10%; p=0.009) and sub-RPE fluid (65% vs 47%; p<0.001). At 1 year, VA was similar in both groups; more eyes with baseline HE had no fluid (45% vs 29%; p<0.001) and greater reduction in total foveal thickness (-266µm vs -158u; p<0.001). 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. CONCLUSION: 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.

Rydberg-atom based radio-frequency electrometry using frequency modulation spectroscopy in room temperature vapor cells.

Rydberg atom-based electrometry enables traceable electric field measurements with high sensitivity over a large frequency range, from gigahertz to terahertz. Such measurements are particularly useful for the calibration of radio frequency and terahertz devices, as well as other applications like near field imaging of electric fields. We utilize frequency modulated spectroscopy with active control of residual amplitude modulation to improve the signal to noise ratio of the optical readout of Rydberg atom-based radio frequency electrometry. Matched filtering of the signal is also implemented. Although we have reached similarly, high sensitivity with other read-out methods, frequency modulated spectroscopy is advantageous because it is well-suited for building a compact, portable sensor. In the current experiment, ∼3 µV cm-1 Hz-1/2 sensitivity is achieved and is found to be photon shot noise limited.

Atom-Based Sensing of Weak Radio Frequency Electric Fields Using Homodyne Readout.

We utilize a homodyne detection technique to achieve a new sensitivity limit for atom-based, absolute radio-frequency electric field sensing of 5 µV cm-1 Hz-1/2. A Mach-Zehnder interferometer is used for the homodyne detection. With the increased sensitivity, we investigate the dominant dephasing mechanisms that affect the performance of the sensor. In particular, we present data on power broadening, collisional broadening and transit time broadening. Our results are compared to density matrix calculations. We show that photon shot noise in the signal readout is currently a limiting factor. We suggest that new approaches with superior readout with respect to photon shot noise are needed to increase the sensitivity further.

SYSTEMIC BETA-BLOCKERS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate whether oral beta-blockers (BBs) are associated with a decreased number of intravitreal injections in patients with incident neovascular age-related macular degeneration. METHODS: A retrospective cohort study of subjects with a new diagnosis of neovascular age-related macular degeneration was conducted using a medical claims database from a large national US insurer. Two cohorts were created for comparison consisting of patients with regular use of BBs or calcium channel blockers. The main outcome measured was the difference in the mean number of intravitreal injections administered between the two cohorts. RESULTS: After inclusion and exclusion criteria, 239 BB and 155 calcium channel blocker subjects remained for analysis. Univariate analysis revealed that the mean number of injections in the BB cohort was 6.43 (95% confidence interval [CI] 5.90-6.95) versus 6.55 (95% CI 5.85-7.25) in the calcium channel blocker cohort (P = 0.78). After multivariate adjustment, the mean number of injections in the BB group was 6.32 (95% CI 5.77-6.87) versus 6.71 (95% CI 6.02-7.40) in the calcium channel blocker group. The overall difference between the 2 groups was -0.39 (95% CI difference -1.29 to 0.51; P = 0.40). CONCLUSION: The use of oral BBs is not associated with a decreased number of intravitreal injections in incident neovascular age-related macular degeneration patients.

Theory of Ultralong-Range Rydberg Molecule Formation Incorporating Spin-Dependent Relativistic Effects: Cs(6s)-Cs(np) as Case Study.

We calculate vibrational spectra of ultralong-range Cs(32p) Rydberg molecules that form in an ultracold gas of Cs atoms. We account for the partial-wave scattering of the Rydberg electrons from the Cs perturber atoms by including the full set of spin-resolved 1,3 SJ and 1,3 PJ scattering phase shifts, and allow for the mixing of singlet (S=0) and triplet (S=1) spin states through Rydberg electron spin-orbit and ground state electron hyperfine interactions. Excellent agreement with observed data in Saßmannshausen et al. [Phys. Rev. Lett. 2015, 113, 133201] in line positions and profiles is obtained. We also determine the spin-dependent permanent electric dipole moments for these molecules. This is the first such calculation of ultralong-range Rydberg molecules for which all of the relativistic contributions are accounted.

Strong Coupling of Rydberg Atoms and Surface Phonon Polaritons on Piezoelectric Superlattices.

We propose a hybrid quantum system where the strong coupling regime can be achieved between a Rydberg atomic ensemble and propagating surface phonon polaritons on a piezoelectric superlattice. By exploiting the large electric dipole moment and long lifetime of Rydberg atoms as well as tightly confined surface phonon polariton modes, it is possible to achieve a coupling constant far exceeding the relevant decay rates. The frequency of the surface mode can be selected so that it is resonant with a Rydberg transition by engineering the piezoelectric superlattice. We describe a way to observe the Rabi splitting associated with the strong coupling regime under realistic experimental conditions. The system can be viewed as a new type of optomechanical system.

Development of Experimental Myopia in Chicks in a Natural Environment.

PURPOSE: The hypothesis that outdoor exposure might protect against myopia has generated much interest, although available data find only modest clinical efficacy. We tested the effect of outdoor rearing on form-deprivation myopia in chicks, a myopia model markedly inhibited by high-intensity indoor laboratory lighting. METHODS: Unilaterally goggled cohorts of White Leghorn chicks were maintained in a species-appropriate, outdoor rural setting during daylight hours to the extent permitted by weather. Control chicks were reared indoors with incandescent lighting. Besides ocular refraction and ultrasound, we determined dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) content in retina and vitreous and measured mRNA expression levels of selected clock and circadian rhythm-related genes in the retina/RPE. RESULTS: Myopia developed in the goggled eyes of all cohorts. Whereas outdoor rearing lessened myopia by 44% at 4 days, a protective effect was no longer evident at 11 days. Outdoor rearing had no consistent effect on retinal or vitreous content of dopamine or DOPAC. Conforming to prior data on form-deprivation myopia, retina and vitreous levels of DOPAC were reduced in goggled eyes. Compared with contralateral eyes, the retinal expression of clock and circadian rhythm-related genes was modestly altered in myopic eyes of chicks reared indoors or outdoors. CONCLUSIONS: Outdoor rearing of chicks induces only a partial decrease of goggle-induced myopia that is not maintained, without evidence that retinal dopamine metabolism accounts for the partial myopia inhibition under these outdoor conditions. Although modest, alterations in retinal gene expression suggest that studying circadian signals might be informative for understanding refractive mechanisms.

Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration: A Meta-Analysis.

IMPORTANCE: The fellow eye of patients with unilateral neovascular age-related degeneration (nAMD) is at increased risk of developing late AMD. Several cohort studies have evaluated the prevalence of pseudodrusen and the association between pseudodrusen and late AMD in the fellow eye of patients with unilateral nAMD. However, these studies have limited sample sizes and their results are inconsistent. OBJECTIVE: To evaluate the prevalence rate of pseudodrusen, and the association between pseudodrusen and incidence of late AMD (nAMD and geographic atrophy (GA)) in the fellow eye of patients with unilateral nAMD. DATA SOURCES: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to July 2015, as well as other systematic reviews. STUDY SELECTION: All cohort studies for pseudodrusen with late AMD in the fellow eye of patients with unilateral nAMD. DATA EXTRACTION AND SYNTHESIS: The numbers of patients with and without pseudodrusen at baseline and the numbers of incident nAMD and GA during follow up among patients with and without pseudodrusen were independently extracted by 2 authors. The results were pooled using random-effects meta-analysis. Heterogeneity was assessed using the I2 test. MAIN OUTCOME MEASURES: Prevalence rate of pseudodrusen, risk ratios (RRs) and their 95% confidence intervals (95% CIs) for associations between pseudodrusen and the incidence of nAMD and GA in the fellow eye. RESULTS: Five cohort studies (N = 677 patients) from 8 countries across 4 continents were included. The pooled prevalence rate of pseudodrusen in the fellow eye was 48.1% (95% Cl: 36.7-59.5%, I2 = 87%). Pseudodrusen were associated with an increased risk of nAMD (RR = 1.54, 95% Cl: 1.10-2.16, I2 = 42%), GA (RR = 4.70, 95% Cl: 1.22-18.1, I2 = 64%), and late AMD (RR = 2.03, 95% Cl: 1.35-3.06, I2 = 60%). CONCLUSIONS: For patients with unilateral nAMD, pseudodrusen were present in about half of the fellow eyes. The presence of pseudodrusen was associated with a 1.5 times higher risk of developing nAMD, a 4.7 times higher risk of developing GA, and a 2 times higher risk of developing late AMD. Pseudodrusen should be considered in evaluating the risk of late AMD development; however, due to considerable heterogeneity across these studies, a larger study is needed to validate these findings.

Angiographic Cystoid Macular Edema and Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: 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). DESIGN: Prospective cohort study within a randomized clinical trial. PARTICIPANTS: A total of 1185 CATT study subjects. METHODS: 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. MAIN OUTCOME MEASURES: Visual acuity (VA) and total central retinal thickness (CRT) on OCT at baseline, year 1, and year 2. RESULTS: 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, P < 0.001); higher mean total CRT (µm) on OCT (514 vs. 472 vs. 404, P < 0.001); 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%; P < 0.001). CONCLUSIONS: 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.

Projecting Critical Care Beyond the ICU: An Analysis of Tele-ICU Support for Rapid Response Teams.

BACKGROUND: The rapid response team (RRT) concept was developed to improve care for decompensating patients outside of the intensive care unit (ICU) setting. The tele-ICU service (eICU(®)) at Health First Hospitals (Brevard County, FL) has provided tele-critical care support for patients outside the ICU using a mobile platform (the eMobile platform) since 2012. In this study we sought to evaluate the ability of eMobile to support care administered by RRTs. MATERIALS AND METHODS: A retrospective review evaluating mobile cart activations for RRT calls was performed. Data on mobile cart deployments were recorded over a 33-month period from January 2012 through September 2014. RESULTS: Five hundred eighty mobile cart activations for critical care support were initiated by RRTs, and 577 were completed (>99%). For recorded gender, 223 patients (47%) were male, and 248 (53%) patients were female. Mean recorded age was 70 ± 16 years (median, 72 years). The most common patient conditions were respiratory distress (n = 190, 33%), altered mental status (n = 137, 24%) and hypotension (n = 59, 10%). The most common interventions were medication orders (n = 231, 40%) and laboratory studies (n = 92, 29%). For 566 eMobile calls with documented dispositions, 189 patients (33%) were managed without ICU upgrade. No adverse patient outcomes were recorded involving eMobile. Compared with the RRT program in 2009, the last year before testing of eMobile began (2010-2011), addition of tele-critical care support for calendar years 2012 and 2013 increased projected cost avoidance from unnecessary ICU transfers by a mean of 66% above the 2009 baseline. For Fiscal Year 2014, a projected cost avoidance analysis for unnecessary ICU transfers including costs of information technology (IT) support demonstrated a return on investment up to $1.66 for every $1 invested in IT support. CONCLUSIONS: Mobile critical care coupled with RRT is clinically effective and can generate meaningful cost avoidance.