Heart Failure-Type Symptom Score Trajectories in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individuals with CKD to understand the patterns and trajectories of HF-type symptoms in this setting. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF. PREDICTORS: Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and electrocardiographic parameters. OUTCOME: Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where<75 reflects clinically significant symptoms). ANALYTICAL APPROACH: Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership. RESULTS: Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms [average of 81] and clinically significant symptoms [average of 52], respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline), and group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of group 1 was male, without diabetes or obesity, and this group had higher baseline kidney function. A majority of groups 2 and 3 had diabetes and obesity. A majority of group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD). LIMITATIONS: No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption. CONCLUSIONS: Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.

Dioptric differences between clinically determined and metric-optimised refractions for adults with Down syndrome.

PURPOSE: Refractions based on the optimisation of single-value wavefront-derived metrics may help determine appropriate corrections for individuals with Down syndrome where clinical techniques fall short. This study compared dioptric differences between refractions obtained using standard clinical techniques and two metric-optimised methods: visual Strehl ratio (VSX) and pupil fraction tessellated (PFSt), and investigated characteristics that may contribute to the differences between refraction types. METHODS: Thirty adults with Down syndrome (age = 29 ± 10 years) participated. Three refractive corrections (VSX, PFSt and clinical) were determined and converted to vector notation (M, J0 , J45 ) to calculate the dioptric difference between pairings of each type using a mixed model repeated measures approach. Linear correlations and multivariable regression were performed to examine the relationship between dioptric differences and the following participant characteristics: higher order root mean square (RMS) for a 4 mm pupil diameter, spherical equivalent refractive error and Vineland Adaptive Behavior Scales (a measure of developmental ability). RESULTS: The least squares mean estimates (standard error) of the dioptric differences for each pairing were as follows: VSX versus PFSt = 0.51 D (0.11); VSX versus clinical = 1.19 D (0.11) and PFSt versus clinical = 1.04 D (0.11). There was a statistically significant difference in the dioptric differences between the clinical refraction and each of the metric-optimised refractions (p < 0.001). Increased dioptric differences in refraction were correlated with increased higher order RMS (R = 0.64, p < 0.001 [VSX vs. clinical] and R = 0.47, p < 0.001 [PFSt vs. clinical]) as well as increased myopic spherical equivalent refractive error (R = 0.37, p = 0.004 [VSX vs. clinical] and R = 0.51, p < 0.001 [PFSt vs. clinical]). CONCLUSIONS: The observed differences in refraction demonstrate that a significant portion of the refractive uncertainty is related to increased higher order aberrations and myopic refractive error. Methodology surrounding clinical techniques and metric-optimisation based on wavefront aberrometry may explain the difference in refractive endpoints.

Heart failure-type symptom scores in chronic kidney disease: The importance of body mass index.

OBJECTIVES: This analysis sought to determine factors (including adiposity-related factors) most associated with HF-type symptoms (fatigue, shortness of breath, and edema) in adults with chronic kidney disease (CKD). BACKGROUND: Symptom burden impairs quality of life in CKD, especially symptoms that overlap with HF. These symptoms are common regardless of clinical HF diagnosis, and may be affected by subtle cardiac dysfunction, kidney dysfunction, and other factors. We used machine learning to investigate cross-sectional relationships of clinical variables with symptom scores in a CKD cohort. METHODS: Participants in the Chronic Renal Insufficiency Cohort (CRIC) with a baseline modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score were included, regardless of prior HF diagnosis. The primary outcome was Overall Summary Score as a continuous measure. Predictors were 99 clinical variables representing demographic, cardiac, kidney and other health dimensions. A correlation filter was applied. Random forest regression models were fitted. Variable importance scores and adjusted predicted outcomes are presented. RESULTS: The cohort included 3426 individuals, 10.3% with prior HF diagnosis. BMI was the most important factor, with BMI 24.3 kg/m2 associated with the least symptoms. Symptoms worsened with higher or lower BMIs, with a potentially clinically relevant 5 point score decline at 35.7 kg/m2 and a 1-point decline at the threshold for low BMI, 18.5 kg/m2. The most important cardiac and kidney factors were heart rate and eGFR, the 4th and 5th most important variables, respectively. Results were similar for secondary analyses. CONCLUSIONS: In a CKD cohort, BMI was the most important feature for explaining HF-type symptoms regardless of clinical HF diagnosis, identifying an important focus for symptom directed investigations.

Avoidable emergency department visits for rabies vaccination.

BACKGROUND: Administering subsequent doses of rabies vaccine is not a medical emergency and does not require access to emergency department (ED) services. This study reviewed ED visits for rabies postexposure prophylaxis (PEP) to identify avoidable ED visits for subsequent rabies vaccination. METHODS: This retrospective study included patients who received human rabies immune globulin (HRIG) or rabies vaccine at 15 EDs of a multi-hospital health system from 2016 to 2018. All ED visits were classified as initial or non-initial healthcare visits after animal exposure. Emergency department visits for non-initial healthcare were classified as necessary (HRIG administration, worsening symptoms, other emergent conditions, or vaccination during a natural disaster) or avoidable (rabies vaccination only). RESULTS: This study included 145 patients with 203 ED visits (113 initial and 90 non-initial healthcare visits). Avoidable ED visits were identified for 19% (28 of 145) of patients and 66% (59 of 90) of ED visits for non-initial healthcare. Contributing factors for avoidable ED visits were suboptimal ED discharge instructions to return to the ED for vaccination (n = 20 visits) and patients' inability to coordinate outpatient follow-up (n = 17 visits). Patients with previous avoidable ED visits had a 73% probability for unnecessarily returning to the ED for vaccination. The average number of avoidable ED visits observed per patient was 0.41 (95% CI = 0.25 to 0.56). Since the Centers for Disease Control and Prevention reports that 30,000 to 60,000 Americans initiates rabies PEP each year, we estimate that 7500 to 33,600 avoidable ED visits occur for rabies vaccination in the US each year. CONCLUSIONS: One of 5 patients who received rabies PEP in the ED had avoidable ED visits for subsequent rabies vaccination. This study highlights systemic lack of coordination following ED discharge and barriers to accessing rabies vaccine.

Visual Acuity Outcomes in a Randomized Trial of Wavefront Metric-optimized Refractions in Adults with Down Syndrome.

SIGNIFICANCE: This study reports visual acuity outcomes from a clinical trial investigating an objective refraction strategy that may provide a useful tool for practitioners needing additional strategies to identify refractive corrections for adults with intellectual disability. PURPOSE: Determining refractions for individuals with Down syndrome is challenging because of the presence of elevated refractive error, optical aberrations, and cognitive impairment. This randomized clinical trial evaluated the performance of spectacle corrections determined using clinical techniques and objective refractions derived from wavefront aberration measures. METHODS: Thirty adults with Down syndrome had a clinical refraction determined by a single expert examiner using pre-dilation and post-dilation techniques appropriate for this population. Objective refractions were determined from dilated wavefront aberration measures that were processed post-visit to identify refractions that optimized each of two image quality metrics: pupil fraction tessellated and visual Strehl ratio in the spatial domain. The three refractions were dispensed in random order and worn for 2 months each. The primary outcome measure, binocular visual acuity, was obtained by a masked examiner administering a distance logMAR acuity test. To compare treatment types, mean acuity was compared using a two-sided type 3 F test of the treatment effect in a linear mixed-effects regression model, where the final model included fixed effects for treatment, period (1, 2, or 3), and first-order carryover effects. RESULTS: The 2-month estimated least square means in binocular visual acuity (logMAR) were 0.34 (95% confidence interval [CI], 0.25 to 0.39) for clinical refractions, 0.31 (95% CI, 0.25 to 0.36) for pupil fraction tesselated refractions, and 0.33 (95% CI, 0.27 to 0.38) for visual Strehl ratio refractions. No statistically significant treatment effect was observed (F = 1.10, P = .34). CONCLUSIONS: Objective refractions derived from dilated wavefront aberration measures resulted in acuity similar to expert clinician-derived refractions, suggesting that the objective method may be a suitable alternative for patients with Down syndrome.

A Randomized Trial of Objective Spectacle Prescriptions for Adults with Down Syndrome: Baseline Data and Methods.

SIGNIFICANCE: It is difficult to determine the most efficacious refractive correction for individuals with Down syndrome using routine clinical techniques. New objective methods that optimize spectacle corrections for this population may reduce limitations on daily living by improving visual quality. PURPOSE: This article describes the methods and baseline characteristics of study participants in a National Eye Institute-sponsored clinical trial to evaluate objectively derived spectacle corrections in adults with Down syndrome. Intersession repeatability of the primary outcome measure (distance visual acuity) is also reported. METHODS: Adults with Down syndrome were enrolled into a nine-visit study to compare clinically derived spectacle corrections and two different objective spectacle corrections derived from wavefront aberration data. Spectacle corrections were randomized and dispensed for 2 months each. Distance visual acuity was measured with a Bailey-Lovie-style chart. Intersession repeatability of acuity was established by performing difference versus mean analysis from binocular acuity measures obtained through habitual corrections at visits 1 and 2. RESULTS: Thirty adults (mean ± standard deviation age, 29 ± 10 years) with a large range of refractive errors were enrolled. Presenting visual acuity at visit 1 was reduced (right eye, 0.47 ± 0.20 logMAR; left eye, 0.42 ± 0.17 logMAR). The mean difference between visits 1 and 2 was 0.02 ± 0.06 logMAR, with a coefficient of repeatability (1.96 × within-subject standard deviation) of 0.12 logMAR. CONCLUSIONS: This study seeks to investigate new strategies to determine optical corrections that may reduce commonly observed visual deficits in individuals with Down syndrome. The good intersession repeatability of acuity found in this study (six letters) indicates that, despite the presence of reduced acuity, adults with Down syndrome performed the outcome measure for this clinical trial reliably.

Randomized Clinical Trial of Near Visual Performance with Digital Devices Using Spherical and Toric Contact Lenses.

SIGNIFICANCE: Visual demands today incorporate a significant amount of time using digital devices. Results of this randomized crossover study of spherical and toric contact lenses demonstrated that participants were able to read smaller print size more comfortably and preferred toric contact lenses when using digital devices. PURPOSE: The purpose of this study was to assess how toric contact lens correction affects subjective and objective outcomes of astigmatic patients using real-world digital devices. METHODS: Adult participants, aged between 20 and 38 years with -0.75 to -1.50 D of astigmatism were enrolled in this double-masked randomized crossover 10-day study of Alcon Dailies Aqua Comfort Plus Sphere and Toric (Alcon, Geneva, Switzerland) contact lenses. Electronic high- and low-contrast near logMAR visual acuity and contrast sensitivity were tested. Reading performance was assessed using custom iPad applications; one used a reading sentences test, whereas the other analyzed zoom, contrast, and distance with website-based articles. Participants completed the Near Activity Visual Questionnaire and stated their preferred contact lens correction. RESULTS: Thirty seven participants were screened, 35 participants were enrolled, and 34 participants completed the study. Toric lens correction improved near high- and low-contrast visual acuity by 0.5 to 1 full line (P < .0001) and allowed participants to read one line smaller text on the iPad (P = .01). Participants increased the zoom 11% (P = .004) and the contrast 4% (P = .006) more with spherical lenses while reading articles. Participants held the iPad at approximately the same distance, about 33 cm (P = .63). Eighty five percent of participants preferred the toric correction (P < .0001). Participants reported improved satisfaction with toric lens correction (P = .0002) and noticed the most benefit with tasks such as reading small print and labels/instructions. CONCLUSIONS: This study used digital devices to demonstrate realistic benefits of toric contact lens designs for astigmatic patients.

Impact of simulated micro-scotomas on reading performance in central and peripheral retina.

Observers with central field loss typically fixate within a non-foveal region called the preferred retinal locus, which can include localized sensitivity losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we simulated micro-scotomas at the fovea and in the peripheral retina to assess their impact on reading speed. Ten younger (<36 years old) and 8 older (>50 years old) naïve observers with normal vision monocularly read high and/or low contrast sentences, presented at or above the critical print size for young observers at the fovea and at 5 and 10 deg in the inferior visual field. Reading material comprised MNREAD sentences and sentences taken from novels that were presented in rapid serial visual presentation (RSVP) format. Randomly distributed 13 × 13 arc min blocks corresponding to 0-78% of the text area (corresponding to ∼0-17 micro-scotomas/deg2) were set to the background luminance to simulate micro-scotomas. A staircase algorithm estimated maximum reading speed from the threshold exposure duration for each combination of retinal eccentricity, contrast and micro-scotoma density in both age groups. Log10(RSVP reading speed) decreased significantly with simulated micro-scotoma density and eccentricity. Across conditions, reading speed was slower with low-compared to high-contrast text and was faster in younger than older normal observers. For a given eccentricity and contrast, a higher density of random element losses maximally affected older observers with normal vision. These outcomes may explain some of the reading deficits observed in older observers with central field loss.

Longitudinal Changes in Disability Rating Scale Scores: A Secondary Analysis Among Patients With Severe TBI Enrolled in the Epo Clinical Trial.

OBJECTIVES: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. METHODS: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. RESULTS: The inter-quartile range (25th-75th percentile) of DRS scores was 20-28 at week1; 8-24 at week 4; and 3-17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. CONCLUSIONS: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293-301).

Refining Psychological, Substance Use, and Sociodemographic Predictors of Suicide Ideation and Attempts in a National Multiethnic Sample of Adults, 2008-2013.

The purpose of this study was to examine psychological, substance use, and sociodemographic predictors of 12-month suicide ideation and attempts across six US racial/ethnic groups-white, Latino/a, Black, Asian or Pacific Islander (A/PI), American Indian or Alaska Native (AI/AN), and multiracial adults. Multiple logistic regression analyses were conducted for 218,765 adults who participated in the 2008-2013 National Survey on Drug Use and Health. Overall, commonly cited factors were associated with increased risk for suicide ideation and attempt for some racial/ethnic groups, but not for others. As one example, 12-month depression was associated with 12-month suicide attempt for A/PI, AI/AN, Latino/a, and white, but not for Black or multiracial adults. Alcohol abuse and dependence were also associated with suicide attempt for AI/AN, Black, and white respondents but not for other racial/ethnic groups. Risk factors for suicide ideation and attempt may not increase risk universally. More theoretically supported research is needed.

Application of Topographical Keratoconus Detection Metrics to Eyes of Individuals with Down Syndrome.

SIGNIFICANCE: The challenges associated with clinical assessment of individuals with Down syndrome contribute to a wide range of estimates on the prevalence of keratoconus in the Down syndrome population. This work focuses on two topographical indices previously identified with keratoconus detection, applying them to a topographical data set meeting strict sampling criteria. PURPOSE: The purpose of this study was to quantify the level of keratoconus-like topographical morphology in a large sample of eyes from individuals with Down syndrome, as identified by two keratoconus detection metrics: inferior-superior dioptric asymmetry (I-S) and KISA%. Severity of the asymmetry was also cast within the context of established Collaborative Longitudinal Evaluation of Keratoconus study disease severity classification criteria. METHODS: Corneal topography data on both eyes of 140 subjects with Down syndrome and 138 control subjects were collected. Both I-S and KISA% were calculated from the topography data of eyes with sufficient sampling. Steep and flat keratometry data are reported for subjects with measurements on both eyes in the context of values recorded by the Collaborative Longitudinal Evaluation of Keratoconus study in frank keratoconus to examine within-eye and between-eye asymmetry and severity. RESULTS: Keratoconus detection thresholds were exceeded in 20.8% of the eyes of subjects with Down syndrome and 2.2% of the eyes of controls using I-S and 11.8% of the eyes of subjects with Down syndrome and 0.0% of the eyes of controls using KISA%. Examination of the level of intraeye difference between flat and steep keratometry data for individuals with Down syndrome detected as having corneal morphology consistent with moderate keratoconus yields an average of 1.81 D of toricity, whereas the Collaborative Longitudinal Evaluation of Keratoconus study reported 3.28 D of toricity. CONCLUSIONS: Morphology consistent with keratoconus as codified in the detection metrics I-S and KISA% is present in a large percentage of the eyes of individuals with Down syndrome. Differences were observed in the distribution of severity of corneal morphology in individuals with Down syndrome and the keratoconus population at large.

Objectively Measured Light Exposure During School and Summer in Children.

SIGNIFICANCE: Significant differences in light exposure were observed between school and summer in children, whereas activity and sleep were similar. Associations between parent and child behaviors suggest a potential mechanism for how myopia is transmitted from parents to children through patterns of environmental exposure, in addition to genetic factors. PURPOSE: Objectively measured time outdoors, light exposure, activity, and sleep were examined in children during school and summer and assessed with eye growth. Associations between parent and child behaviors were evaluated. METHODS: Children (aged 7.6 ± 1.8 years, n = 60) in Houston, TX, wore an actigraph device for three 2-week sessions (fall school, spring school, summer) to quantify time outdoors, light exposure, activity, and sleep. Cycloplegic autorefraction (WAM-5500; Grand-Seiko, Tokyo, Japan) and axial length (LenStar; Haag-Streit AG, Koeniz, Switzerland) were measured at baseline and 1 year. A subset of parents wore the device during their child's first 2-week session to compare behaviors (n = 33). RESULTS: Children spent 94.4 ± 30.6 minutes per day outdoors in spring, 110.6 ± 45.7 minutes in summer, and 72.2 ± 31.0 minutes in fall, with significant differences between sessions (P < .0001). Daily activity and sleep duration were similar across sessions (P = .73 and .06, respectively). Axial growth rate decreased with light exposure, but did not reach significance after adjusting for baseline axial length, age, sex, activity, and parental myopia (P = .073). Parent and child time outdoors and sleep duration were significantly correlated (P = .0002 and 0.026, respectively). CONCLUSIONS: Significant differences in light exposure were observed between school and summer, whereas activity and sleep were constant throughout the year. Children's behaviors were associated with their parent's behaviors, which may represent a modifiable component to potential environmental influences on eye growth. However, light exposure was not a significant environmental influence on axial growth in this study.

Repeatability of Monocular Acuity Testing in Adults with and without Down Syndrome.

PURPOSE: Individuals with Down syndrome may experience greater difficulty reliably performing visual acuity (VA) tests because of intellectual disability and limitations in visual quality. This study evaluated the repeatability of acuity (Bailey-Lovie [BL] and HOTV) in subjects with and without Down syndrome. METHODS: High-contrast VA was measured in both eyes of 30 subjects with Down syndrome (mean, 30 years; range, 18 to 50 years) and 24 control subjects without Down syndrome (mean, 29 years; range, 18 to 50 years). In the Down syndrome group, 23 subjects performed BL, and 7 subjects performed HOTV. All control subjects performed both BL and HOTV, but for HOTV analysis, only seven age-matched control subjects were included. For each eye, subjects performed VA three times on different charts (computer controlled, single-line display) until five total letters were missed on each chart. A repeated-measure ANOVA was used to compare the acuity measures between groups. RESULTS: The average logMAR VA for subjects with Down syndrome was approximately six lines worse than the control subjects (BL: Down syndrome = right eye: 0.51 ± 0.16, left eye: 0.53 ± 0.18; control = right eye: -0.06 ± 0.06, left eye: -0.06 ± 0.08, P < .0001; HOTV: Down syndrome = right eye: 0.47 ± 0.19, left eye: 0.46 ± 0.16; control: right eye = -0.11 ± 0.09, left eye: -0.07 ± 0.07, P < .001). Bailey-Lovie VA repeatability (1.96 * Sw * √2) was 0.13 logMAR (6.5 letters) for Down syndrome and 0.09 logMAR (4.5 letters) for control subjects. HOTV VA repeatability was 0.16 logMAR (eight letters) for both Down syndrome and control subjects. CONCLUSIONS: Despite poorer acuity in individuals with Down syndrome, repeatability of VA measurements was comparable to control subjects for both BL and HOTV techniques.

Impact of Cognitive Demand during Sustained Near Tasks in Children and Adults.

SIGNIFICANCE: These results demonstrate that accommodation in children is more accurate and less variable when performing a sustained near task with increased cognitive demand. In addition, children with increased uncorrected hyperopia have less stable accommodative responses, which may have visual implications during sustained near tasks. PURPOSE: This study investigated accommodative accuracy (lag) and variability during sustained viewing for passive and active tasks in children and adults with emmetropia and uncorrected hyperopia. METHODS: Lag and variability (root mean square [RMS] and low-frequency component) were measured in 54 children aged 3 to younger than 10 years with mean spherical equivalent of +1.31 ± 1.05 diopters (D) (range, -0.37 to +4.58 D) and 8 adults aged 22 to 32 years with mean spherical equivalent +0.65 ± 0.62 D (range, -0.13 to +1.15 D). Subjects viewed 20/50 stimuli at 33 cm during both a 10-minute passive and active task. Group 1 (<6 years or nonreaders) viewed shapes; group 2 (≥6 years and reading) and adults read passages. RESULTS: Groups 1 and 2 had larger lags, RMS, and low-frequency component for passive versus active tasks (P < .001). Lag and RMS did not differ between tasks in adults (P > .05), but low-frequency component was larger during passive viewing (P = .04). Group 1 had significantly higher RMS and low-frequency component than group 2 and the adults in the passive condition had greater low-frequency component in the active condition. In children, hyperopia was independently associated with RMS and low-frequency component under passive (RMS 95% confidence interval [CI], 0.04 to 0.15; low-frequency component 95% CI, 0.00011 to 0.00065) and active (RMS 95% CI, 0.001 to 0.06; 95% CI, 0.000014 to 0.00023) viewing. CONCLUSIONS: Accommodation is more accurate and less variable when children are engaged in the task. Children also have more variable accommodation than adults. In addition, children with greater hyperopia have more variable accommodation during sustained near tasks.

Blur Detection, Depth of Field, and Accommodation in Emmetropic and Hyperopic Children.

SIGNIFICANCE: Our results demonstrate that blur detection thresholds are elevated in young children compared with adults, and poorer blur detection thresholds are significantly correlated with the magnitude of accommodative microfluctuations. Given that accommodative microfluctuations are greater with greater accommodative responses, these findings may have implications for young uncorrected hyperopes. PURPOSE: This study investigated the association between subjective blur detection thresholds and accommodative microfluctuations in children 3 years to younger than 10 years old and adults. METHODS: Blur detection thresholds were determined in 49 children with habitually uncorrected refractive error (+0.06 to +4.91 diopters [D] spherical equivalent) and 10 habitually uncorrected adults (+0.08 to +1.51 D spherical equivalent) using a custom blur chart with 1° sized optotypes at 33 cm. Letters were blurred by convolution using a Gaussian kernel (SDs of 0.71 to 11.31 arc minutes in √2 steps). Subjective depth of field was determined in subjects 6 years or older and adults. Accommodative microfluctuations, pupils, and lag were measured using infrared photorefraction (25 Hz). RESULTS: Children had greater blur detection thresholds (P < .001), accommodative microfluctuations (P = .001), and depth of field (P < .001) than adults. In children, increased blur detection thresholds were associated with increased accommodative microfluctuations (P < .001), increased uncorrected hyperopia (P = .01), decreased age (P < .001), and decreased pupil size (P = .01). In a multiple linear regression analysis, blur detection thresholds were associated with accommodative microfluctuations (P < .001) and age (P < .001). Increased accommodative microfluctuations were associated with increased uncorrected hyperopia (P = .004) and decreased pupil size (P = .003) and independently associated with uncorrected hyperopia (P = .001) and pupil size (P = .003) when controlling for age and lag. CONCLUSIONS: Children did not have adult-like blur detection thresholds or depth of field. Increased accommodative microfluctuations and decreased age were independently associated with greater blur detection thresholds in children 3 years to younger than 10 years. Larger amounts of uncorrected hyperopia in children appear to increase blur detection thresholds because the greater accommodative demand and resulting response increase accommodative microfluctuations.

Extending the Simple View of Reading to Account for Variation Within Readers and Across Texts: The Complete View of Reading (CVRi).

This study leverages advances in multivariate cross-classified random effects models to extend the Simple View of Reading to account for variation within readers and across texts, allowing for both the personalization of the reading function and the integration of the component skills and text and discourse frameworks for reading research. We illustrate the Complete View of Reading (CVRi) using data from an intensive longitudinal design study with a large sample of typical (N = 648) and struggling readers (N = 865) in middle school and using oral reading fluency as a proxy for comprehension. To illustrate the utility of the CVRi, we present a model with cross-classified random intercepts for students and passages and random slopes for growth, Lexile difficulty, and expository text type at the student level. We highlight differences between typical and struggling readers and differences across students in different grades. The model illustrates that readers develop differently and approach the reading task differently, showing differential impact of text features on their fluency. To be complete, a model of reading must be able to reflect this heterogeneity at the person and passage level, and the CVRi is a step in that direction. Implications for reading interventions and 21st century reading research in the era of "Big Data" and interest in phenotypic characterization are discussed.

Spherical Soft Contact Lens Designs and Peripheral Defocus in Myopic Eyes.

PURPOSE: Peripheral retinal defocus has been implicated in myopia progression. The effect of commercially available spherical soft contact lenses (SCLs) on peripheral defocus of adult myopic eyes was investigated. METHODS: Twenty-five young adults with spherical equivalent (SE) refractions between -0.50D and -6.00D were enrolled. Cycloplegic autorefraction (right eye) was measured centrally and ±20°, ±30°, and ±40° from the line of sight along the horizontal meridian using an autorefractor. Four commercially available spherical SCLs (Biofinity, Acuvue2, PureVision2, and Air Optix Night & Day Aqua) were evaluated. SE defocus (M) was used to calculate relative peripheral defocus (RPD) while wearing each SCL and relative peripheral refraction of the uncorrected eye. Spherical aberration (SA) changes caused by each SCL were measured along the line of sight by aberrometry. Peripheral defocus was analyzed using repeated-measures analyses of variance (RM-ANOVA). The association between changes in axial SA and the change in peripheral defocus was evaluated using linear mixed models. RESULTS: The mean age (±SD) and central SE refractive error were 24.0 ± 1.3 years and -3.45 ± 1.42D, respectively. PureVision2 did not change RPD (P = .33). Significant myopic shifts on the temporal retina were found with three lenses: Acuvue 2 (-0.29D at 30°; -0.80D at 40°; both P ≤ .01), Biofinity (-1.21 D at 40°; P = .02), and Air Optix Night & Day Aqua (-0.23D at 20°, -0.48D at 30°, and -1.50D at 40°; all P < .004). All SCLs caused a negative change in SA. SCLs inducing less negative (more positive) SA changes were associated with a less hyperopic change in RPD. CONCLUSIONS: Spherical SCL design can influence the peripheral defocus profile experienced by a myopic eye. Several, but not all, SCLs reduced peripheral hyperopia. Differences in how SCL types influence peripheral defocus may have implications for myopia progression.

Variability in Objective Refraction for Persons with Down Syndrome.

PURPOSE: Down syndrome (DS) is associated with ocular and cognitive sequelae, which both have the potential to influence clinical measures of refractive error. This study compares variability of autorefraction among subjects with and without DS. METHODS: Grand Seiko autorefraction was performed on 139 subjects with DS (age: 8-55, mean: 25 ± 9 yrs) and 138 controls (age: 7-59, mean: 25 ± 10 yrs). Subjects with three refraction measures per eye (DS: 113, control: 136) were included for analysis. Each refraction was converted to power vector notation (M, J0, J45) and a difference in each component (ΔM, ΔJ0, ΔJ45) was calculated for each refraction pairing. From these quantities, average dioptric strength ((Equation is included in full-text article.): square root of the sum of the squares of M, J0, and J45) and average dioptric difference ((Equation is included in full-text article.): square root of the sum of the squares of ΔM, ΔJ0, and ΔJ45) were calculated. RESULTS: The DS group exhibited a greater median (Equation is included in full-text article.)(1Q: 1.38D M: 2.38D 3Q: 3.41D) than control eyes (1Q: 0.47D M: 0.96D 3Q: 2.75D) (P < .001). Likewise, the DS group exhibited a greater median (Equation is included in full-text article.)in refraction (1Q: 0.27D M: 0.42D 3Q: 0.78D) than control eyes (1Q: 0.11D M: 0.15D 3Q: 0.23D) (P < .001) with 97.1% of control eyes exhibiting (Equation is included in full-text article.)≤0.50D, compared to 59.3% of DS eyes. An effect of (Equation is included in full-text article.)on (Equation is included in full-text article.)was not detected (P = .3009) nor was a significant interaction between (Equation is included in full-text article.)and group detected (P = .49). CONCLUSIONS: In the current study, comparing three autorefraction readings, median total dioptric difference with autorefraction in DS was 2.8 times the levels observed in controls, indicating greater potential uncertainty in objective measures of refraction for this population. The analysis demonstrates that J45 is highly contributory to the observed variability.

A hidden Markov model approach to analyze longitudinal ternary outcomes when some observed states are possibly misclassified.

Understanding the dynamic disease process is vital in early detection, diagnosis, and measuring progression. Continuous-time Markov chain (CTMC) methods have been used to estimate state-change intensities but challenges arise when stages are potentially misclassified. We present an analytical likelihood approach where the hidden state is modeled as a three-state CTMC model allowing for some observed states to be possibly misclassified. Covariate effects of the hidden process and misclassification probabilities of the hidden state are estimated without information from a 'gold standard' as comparison. Parameter estimates are obtained using a modified expectation-maximization (EM) algorithm, and identifiability of CTMC estimation is addressed. Simulation studies and an application studying Alzheimer's disease caregiver stress-levels are presented. The method was highly sensitive to detecting true misclassification and did not falsely identify error in the absence of misclassification. In conclusion, we have developed a robust longitudinal method for analyzing categorical outcome data when classification of disease severity stage is uncertain and the purpose is to study the process' transition behavior without a gold standard.