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1.  Associations Between Abnormal Rod-Mediated Dark Adaptation and Health and Functioning in Older Adults With Normal Macular Health 
Delayed rod-mediated dark adaptation (DA) is characteristic of early age-related macular degeneration (AMD) and also can be observed in some older adults in normal macular health. We examine cross-sectional associations between rod-mediated DA and risk factors for AMD in older adults in normal macular health.
The sample consisted of adults aged ≥60 years old in normal macular health per grading of fundus photos using an established disease classification system. Rod-mediated DA was measured psychophysically following a photobleach using a computer-automated dark adaptometer with targets centered at 5° on the inferior vertical meridian. The speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥ 12.3 minutes. We assessed several health and functional characteristics that the literature has suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers, apolipoproteins, low luminance visual acuity, chronic medical conditions, body mass, family history).
Among 381 participants (mean age, 68.5 years; SD, 5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA increasing with age. After age-adjustment, abnormal DA was associated with increased odds of elevated C-reactive protein (CRP), heavy use of or abstention from alcohol, high blood pressure, and drop in visual acuity under mesopic conditions.
Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP.
Abnormal rod-mediated dark adaptation in older adults in normal macular health is associated with elevated plasma C-reactive protein levels.
PMCID: PMC4122017  PMID: 24854857
aging; dark adaptation; rod function; age-related macular degeneration
2.  Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium 
Lipofuscin (LF) accumulation within RPE cells is considered pathogenic in AMD. To test whether LF contributes to RPE cell loss in aging and to provide a cellular basis for fundus autofluorescence (AF) we created maps of human RPE cell number and histologic AF.
Retinal pigment epithelium–Bruch's membrane flat mounts were prepared from 20 donor eyes (10 ≤ 51 and 10 > 80 years; postmortem: ≤4.2 hours; no retinal pathologies), preserving foveal position. Phalloidin-binding RPE cytoskeleton and LF-AF (488-nm excitation) were imaged at up to 90 predefined positions. Maps were assembled from 83,330 cells in 1470 locations. From Voronoi regions representing each cell, the number of neighbors, cell area, and total AF intensity normalized to an AF standard was determined.
Highly variable between individuals, RPE-AF increases significantly with age. A perifoveal ring of high AF mirrors rod photoreceptor topography and fundus-AF. Retinal pigment epithelium cell density peaks at the fovea, independent of age, yet no net RPE cell loss is detectable. The RPE monolayer undergoes considerable lifelong re-modeling. The relationship of cell size and AF, a surrogate for LF concentration, is orderly and linear in both groups. Autofluorescence topography differs distinctly from the topography of age-related rod loss.
Digital maps of quantitative AF, cell density, and packing geometry provide metrics for cellular-resolution clinical imaging and model systems. The uncoupling of RPE LF content, cell number, and photoreceptor topography in aging challenges LF's role in AMD.
Simultaneous RPE cell density and autofluorescence maps of human donor eyes exhibit a significant increase in lipofuscin autofluorescence with age while RPE cell density remains stable, questioning lipofuscin's role in aging and AMD.
PMCID: PMC4123894  PMID: 25034602
retinal pigment epithelium; autofluorescence; photoreceptor; lipofuscin; cytoskeleton
3.  Agreement in Assessing Cup-to-Disc Ratio Measurement Among Stereoscopic Optic Nerve Head Photographs, HRT II, and Stratus OCT 
Journal of glaucoma  2006;15(3):183-189.
To compare the level of agreement between subjective and objective methods in estimating horizontal and vertical cupto-disc ratios (HCDR and VCDR, respectively) to determine if objective techniques may be used as surrogates for subjective cup-to-disc (CDR) estimation.
Fifty-one glaucoma patients and 49 control subjects underwent full ophthalmic examination, stereoscopic optic nerve head photographs (ONHPs), confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomography II [HRT II]), and optical coherence tomography (Stratus OCT). The intra-class correlation coefficient (ICC) and Bland Altman plots were used to assess the agreement across the three methods. Repeated measures analysis of variance (ANOVA), Tukey adjustment, and pairwise P values were used to compare the HCDR and VCDR estimates between three clinicians who reviewed photos, Stratus OCT, and HRT II.
For the clinicians, the agreement in subjectively assessed HCDR and VCDR was substantial (ICC = 0.84 and 0.85, respectively), and for all three methods, overall agreement was good (ICC = 0.75 and 0.77 for the HCDR and VCDR, respectively). Stratus OCT provided the largest overall mean ± SD HCDR (0.68 ± 0.14) and VCDR (0.62 ± 0.13). The smallest overall mean ± SD HCDR was provided by ONHP (0.32 ± 0.16), and the smallest overall mean ± SD VCDR was provided by HRT II (0.26 ± 0.20). Repeated measures ANOVA test demonstrated significant differences across the three methods for glaucomatous (P = 0.0017 and 0.0016, HCDR and VCDR, respectively) and normal (P = 0.0001 for both HCDR and VCDR) eyes. Tukey adjustment demonstrated specific statistical differences between pairs of methods.
Although the overall agreement between various methods was good, the mean estimates were statistically different. Additional studies are needed to evaluate the sources of variability, their level of significance, and longitudinal agreement between various methods of the CDR estimation.
PMCID: PMC4302161  PMID: 16778638
cup-to-disc ratio; HRT II; Stratus OCT; stereoscopic optic nerve head photographs
4.  Patient versus parental perceptions about pain and disability in children and adolescents with a variety of chronic pain conditions 
Cross-informant variance is often observed in patient self-reports versus parent proxy reports of pediatric chronic pain and disability.
To assess the relationship and merit of the child versus parent perspective.
A total of 99 patients (eight to 17 years of age [mean 13.2 years]; 71% female, 81% Caucasian) and parents completed the Pediatric Pain Questionnaire and Functional Disability Inventory at their initial clinic visit. Patients’ and parents’ pain intensity and disability scores were analyzed using an intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, Bland-Altman plot and Spearman’s correlation coefficient. The association between clinical/demographic variables and differences in patient/parent pain intensity and disability scores was assessed using multivariable regression.
There was significant agreement between patients’ self-reports and parents’ proxy reports of their child’s pain intensity (ICC=0.52; P<0.001) and disability (ICC=0.57; P=0.004) at the individual level. There were no significant group differences in patient versus parent-proxy pain intensity scores (P=0.40) and disability scores (P=0.54). The difference between patient and parent-proxy pain intensity was associated with patients’ self-reported pain intensity (P<0.001). The difference between patient and parent-proxy disability was associated with patient’s self-reported pain disability (P<0.001). Bland-Altman plots revealed major inter-rater variation in the Pediatric Pain Questionnaire and Functional Disability Inventory across their score ranges. A significant relationship (r=0.38; P<0.001) was observed between patients’ self-reported pain intensity and disability.
While equal merit should ideally be given to pediatric chronic pain patients’ self-reports and their parents’ proxy reports of pain intensity and disability, it would appear that, as needed, pediatric patients or parents can offer a clinically valid, single clinical perspective.
PMCID: PMC3938337  PMID: 24147272
Adolescents; Children; Chronic pain; Disability; Functional capacity; Pain intensity; Parent-child; Pediatrics
5.  A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus 
Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis.
We genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects.
In the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10−5, false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58–3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10−4) and European Americans (OR 3.47, P = 0.024).
TLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation.
PMCID: PMC4269184  PMID: 24578102
6.  Reducing Older Driver Motor Vehicle Collisions via Earlier Cataract Surgery 
Accident; analysis and prevention  2013;61:10.1016/j.aap.2013.01.002.
Older adults who undergo cataract extraction have roughly half the rate of motor vehicle collision (MVC) involvement per mile driven compared to cataract patients who do not elect cataract surgery. Currently in the U.S., most insurers do not allow payment for cataract surgery based upon the findings of a vision exam unless accompanied by an individual’s complaint of visual difficulties that seriously interfere with driving or other daily activities and individuals themselves may be slow or reluctant to complain and seek relief. As a consequence, surgery tends to occur after significant vision problems have emerged. We hypothesize that a proactive policy encouraging cataract surgery earlier for a lesser level of complaint would significantly reduce MVCs among older drivers. We used a Monte Carlo model to simulate the MVC experience of the U.S. population from age 60 to 89 under alternative protocols for the timing of cataract surgery which we call “Current Practice” (CP) and “Earlier Surgery” (ES). Our base model finds, from a societal perspective with undiscounted 2010 dollars, that switching to ES from CP reduces by about 21% the average number of MVCs, fatalities, and MVC cost per person. The net effect on total cost – all MVC costs plus cataract surgery expenditures -- is a reduction of about 16%. Quality Adjusted Life Years would increase by about 5%. From the perspective of payers for healthcare, the switch would increase cataract surgery expenditure for ages 65+ by about 8% and for ages 60 to 64 by about 47% but these expenditures are substantially offset after age 65 by reductions in the medical and emergency services component of MVC cost. Similar results occur with discounting at 3% and with various sensitivity analyses. We conclude that a policy of ES would significantly reduce MVCs and their associated consequences.
PMCID: PMC3644302  PMID: 23369786
Motor Vehicle Collision; Cataract Surgery; Monte Carlo Simulation; Elderly; Cost Effectiveness; Medicare; Insurance
7.  Value of Isolated IgA anti-β2GPI Positivity in the Diagnosis of the Antiphospholipid Syndrome 
Arthritis and rheumatism  2013;65(12):3186-3193.
To examine the prevalence of isolated IgA anti-β2Glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the Antiphospholipid Syndrome (APS) in three patients groups. The pathogenicity of IgA anti-β2GPI was also evaluated in a mouse model of thrombosis.
Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n=558), patients with SLE from the Hopkins Lupus Cohort (n=215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n=5,098) were evaluated. IgA anti-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti- β2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.
A total of 198 patients were found to be positive for IgA anti-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2GPI positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI positivity was associated with an increased risk for arterial thrombosis (p<0.001), venous thrombosis (p=0.015) and all thrombosis (p<0.001). The association between isolated IgA anti-β2GPI and arterial thrombosis (p=0.0003) and all thrombosis (p=0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.
Isolated IgA anti-β2GPI positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid (aPL) tests are negative and APS is suspected is recommended. IgA anti-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.
PMCID: PMC4048705  PMID: 23983008
9.  Histologic Characteristics of the Fetal Inflammatory Response Associated with Neurodevelopmental Impairment and Death in Extremely Preterm Infants 
The Journal of pediatrics  2013;163(3):652-657.e2.
To test the hypothesis that increasing severity of the fetal inflammatory response would have a dose-dependent relationship with severe neurodevelopmental impairment (NDI) or death in extremely preterm infants.
Study design
We report 347 infants 23 to 28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or NDI at 18–22 month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1: phlebitis; stage 2: arteritis with or without phlebitis; stage 3: subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis).
A fetal inflammatory response was detected in 110 placentas (32%). Severe NDI/death rate was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs. 35%; p<0.05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with higher rates of severe NDI/death (47% vs. 23%; p<0.05). After adjustment for confounding factors, only subacute necrotizing funisitis (RR: 1.87; 95% CI: 1.04 – 3.35; p=0.04) and chorionic plate vasculitis with thrombosis (RR: 2.21; 95% CI: 1.10 – 4.46; p=0.03) were associated with severe NDI/death.
Severe fetal inflammatory response characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis are associated with severe NDI/death in preterm infants.
PMCID: PMC3744601  PMID: 23664630
chorioamnionitis; infant; premature; prognosis; funisitis; chorionic plate vasculitis
10.  Examining the Association Between Age-Related Macular Degeneration and Motor Vehicle Collision Involvement: A Retrospective Cohort Study 
The British journal of ophthalmology  2013;97(9):10.1136/bjophthalmol-2013-303601.
Little is known about motor vehicle collision (MVC) risk in older drivers with age-related macular degeneration (AMD). The purpose of this study is to examine associations between MVC involvement and AMD presence and severity.
In a retrospective cohort study pooling the samples from four previous studies, we examined associations between MVC rate and older drivers with early, intermediate, or advanced AMD as compared to those in normal eye health. MVC data were based on accident reports obtained from the state agency that compiles this information.
MVC rate was highest among those in normal eye health and progressively declined among those with early and intermediate disease, and then increased for those with advanced AMD. However, only for drivers with intermediate AMD was the MVC rate significantly different (lower) as compared to those in normal eye health, regardless of whether the rate was defined in terms of person-years (RR 0.34, 95% CI 0.13–0.89) or person-miles (RR 0.35, 95% CI 0.13–0.91) of driving.
These results suggest that older drivers with intermediate AMD have a reduced risk of collision involvement. Further research should investigate whether self-regulatory driving practices by these drivers (avoiding challenging driving situations) underlies this reduced risk.
PMCID: PMC3837568  PMID: 23832967
driving; age-related macular degeneration; vision impairment
11.  Functional status, life-space mobility, and quality of life: a longitudinal mediation analysis 
Using the Wilson–Cleary model of patient outcomes as a conceptual framework, the impact of functional status on health-related quality of life (HRQoL) among older adults was examined, including tests of the mediation provided by life-space mobility.
Participants were enrollees in a population-based, longitudinal study of mobility among community-dwelling older adults. Data from four waves of the study equally spaced approximately 18 months apart (baseline, 18, 36, and 54 months) were used for participants who survived at least 1 year beyond the 54-month assessment (n = 677). Autoregressive mediation models using longitudinal data and cross-sectional mediation models using baseline data were evaluated and compared using structural equation modeling.
The longitudinal autoregressive models supported the mediating role of life-space mobility and suggested that this effect is larger for the mental component summary score than the physical component summary score of the SF-12. Evidence for a reciprocal relationship over time between functional status, measured by ADL difficulty, and life-space mobility was suggested by modification indices; these model elaborations did not alter the substantive meaning of the mediation effects. Mediated effect estimates from longitudinal autoregressive models were generally larger than those from cross-sectional models, suggesting that mediating relationships would have been missed or were potentially underestimated in cross-sectional models.
These results support a mediating role for life-space mobility in the relationship between functional status and HRQoL. Functional status limitations might cause diminished HRQoL in part by limiting mobility. Mobility limitations may precede functional status limitations in addition to being a consequence thereof.
PMCID: PMC3618999  PMID: 23161329
Wilson; Cleary model; Activities of daily living; Mobility; SF-12; Longitudinal mediation; Autoregressive mediation modeling
12.  Effectiveness of Booster Seats Compared With No Restraint or Seat Belt Alone for Crash Injury Prevention 
The objective was to evaluate the effectiveness of belt-positioning booster seats, compared with no restraint use and with seat belt use only, during motor vehicle crashes among U.S. children.
This was a retrospective matched cohort study with data from the 1998 through 2009 National Automotive Sampling System (NASS) Crashworthiness Data System (CDS). The study sample consisted of children aged 0 to 10 years who were not seated in the front seat of the vehicle. We used Cox proportional hazards models to estimate the risk of overall, fatal, and regional body injury.
Children using seat belts in belt-positioning booster seats experienced less overall injury (Injury Severity Score [ISS] > 0, adjusted risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.55 to 0.96; Abbreviated Injury Scale [AIS] score of 2 or higher, adjusted RR = 0.30, 95% CI = 0.16 to 0.58; ISS > 8, adjusted RR = 0.19, 95% CI = 0.06 to 0.56), and less injury in most body regions except the neck (adjusted RR = 4.79, 95% CI = 1.43 to 16.00) than did children with no restraint use. Children using seat belts in belt-positioning booster seats had an equal risk of injury but higher risks of neck (adjusted RR = 1.86, 95% CI = 1.02 to 3.40) and thorax (adjusted RR = 2.86, 95% CI = 1.33 to 6.15) injury than did children restrained by seat belts only.
Children using belt-positioning booster seats appear to experience a higher risk of AIS > 0 injury to the neck and thorax than do children using seat belts only. Future research should examine whether the observed increase in neck and thorax injuries can be attributed to improper use of booster seats.
PMCID: PMC3798005  PMID: 24050794
13.  Is Familial Lupus Different from Sporadic Lupus?: Data from LUMINA, a Multiethnic US Cohort 
Lupus  2010;19(11):1331-1336.
To characterize the clinical features of familial lupus, and determine its influence on damage accrual and survival using data from LUMINA, a longitudinal multiethnic US cohort.
Familial lupus was defined as patients with a first degree relative with SLE. Relative risks were estimated by logistic regression; odds ratios (OR) and their 95% confidence intervals (CI) were the measure of association for familial lupus. Hazard Ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for damage and survival.
Thirty-two of 644 patients had familial and 612 had sporadic lupus; both groups were of comparable age (~ 36 years). Familial lupus patients were in decreasing order of frequency siblings, parents and children. In multivariable analyses, mucosal ulcers (OR=1.92, 95% CI 0.65–5.70), mitral valve prolapse (OR=1.74, 95% CI 0.50–6.10), cerebrovascular disease (OR=4.18, 95% CI 0.98–17.76) and oral contraceptive use (ever/never; OR=2.51, 95% CI 0.88–7.19) were more likely in familial lupus but a history of low platelet count (<150,000/mm3; OR=0.31, 95% CI 0.08–1.17) and pulmonary disease activity (OR=0.39, 95% CI 0.14–1.20) were less likely. However, none of these associations reached statistical significance. Familial lupus was not significantly associated with a shorter time to either damage accrual or death (HR=0.77, 95% CI 0.37–1.59, p = 0.4746 and HR=0.20, 95% CI 0.03–1.47, p = 0.2020, respectively).
Although some clinical differences were observed in patients with familial and sporadic lupus, familial lupus was not associated with a significantly greater disease burden (damage, survival) than sporadic lupus.
PMCID: PMC4078734  PMID: 20696771
familial lupus; lupus; sporadic lupus; LUMINA; multiethnic cohort
14.  Visually Impaired Drivers Who Use Bioptic Telescopes: Self-Assessed Driving Skills and Agreement With On-Road Driving Evaluation 
To compare self-assessed driving habits and skills of licensed drivers with central visual loss who use bioptic telescopes to those of age-matched normally sighted drivers, and to examine the association between bioptic drivers' impressions of the quality of their driving and ratings by a “backseat” evaluator.
Participants were licensed bioptic drivers (n = 23) and age-matched normally sighted drivers (n = 23). A questionnaire was administered addressing driving difficulty, space, quality, exposure, and, for bioptic drivers, whether the telescope was helpful in on-road situations. Visual acuity and contrast sensitivity were assessed. Information on ocular diagnosis, telescope characteristics, and bioptic driving experience was collected from the medical record or in interview. On-road driving performance in regular traffic conditions was rated independently by two evaluators.
Like normally sighted drivers, bioptic drivers reported no or little difficulty in many driving situations (e.g., left turns, rush hour), but reported more difficulty under poor visibility conditions and in unfamiliar areas (P < 0.05). Driving exposure was reduced in bioptic drivers (driving 250 miles per week on average vs. 410 miles per week for normally sighted drivers, P = 0.02), but driving space was similar to that of normally sighted drivers (P = 0.29). All but one bioptic driver used the telescope in at least one driving task, and 56% used the telescope in three or more tasks. Bioptic drivers' judgments about the quality of their driving were very similar to backseat evaluators' ratings.
Bioptic drivers show insight into the overall quality of their driving and areas in which they experience driving difficulty. They report using the bioptic telescope while driving, contrary to previous claims that it is primarily used to pass the vision screening test at licensure.
Drivers with central vision impairment who use bioptic telescopes have insight into the overall quality of their driving and driving skills with which they have difficulty.
PMCID: PMC3894796  PMID: 24370830
bioptic telescope; driving; low vision
15.  Association Between Depression and Functional Vision Loss in Persons 20 Years of Age or Older in the United States, NHANES 2005–2008 
JAMA ophthalmology  2013;131(5):573-581.
This study provides further evidence from a national sample to generalize the relationship between depression and vision loss to adults across the age spectrum. Better recognition of depression among people reporting reduced ability to perform routine activities of daily living due to vision loss is warranted.
To estimate, in a national survey of US adults 20 years of age or older, the prevalence of depression among adults reporting visual function loss and among those with visual acuity impairment. The relationship between depression and vision loss has not been reported in a nationally representative sample of US adults. Previous studies have been limited to specific cohorts and predominantly focused on the older population.
The National Health and Nutrition Examination Survey (NHANES) 2005–2008.
A cross-sectional, nationally representative sample of adults, with prevalence estimates weighted to represent the civilian, noninstitutionalized US population.
A total of 10 480 US adults 20 years of age or older.
Main Outcome Measures
Depression, as measured by the 9-item Patient Health Questionnaire depression scale, and vision loss, as measured by visual function using a questionnaire and by visual acuity at examination.
In 2005–2008, the estimated crude prevalence of depression (9-item Patient Health Questionnaire score of ≥10) was 11.3% (95% CI, 9.7%–13.2%) among adults with self-reported visual function loss and 4.8% (95% CI, 4.0%–5.7%) among adults without. The estimated prevalence of depression was 10.7% (95% CI, 8.0%–14.3%) among adults with presenting visual acuity impairment (visual acuity worse than 20/40 in the better-seeing eye) compared with 6.8% (95% CI, 5.8%–7.8%) among adults with normal visual acuity. After controlling for age, sex, race/ethnicity, marital status, living alone or not, education, income, employment status, health insurance, body mass index, smoking, binge drinking, general health status, eyesight worry, and major chronic conditions, self-reported visual function loss remained significantly associated with depression (overall odds ratio, 1.9 [95% CI, 1.6–2.3]), whereas the association between presenting visual acuity impairment and depression was no longer statistically significant.
Conclusions and Relevance
Self-reported visual function loss, rather than loss of visual acuity, is significantly associated with depression. Health professionals should be aware of the risk of depression among persons reporting visual function loss.
PMCID: PMC3772677  PMID: 23471505
16.  A Population-Based Examination of the Visual and Ophthalmological Characteristics of Licensed Drivers Aged 70 and Older 
Safe driving performance depends on visual skills yet little is known about the prevalence of vision impairments in older drivers and the eye conditions that cause them. This study is a population-based examination of the prevalence of vision impairment and major ophthalmological conditions among drivers aged 70 and older.
The source population was a random sample of 2,000 licensed drivers aged 70 and older residing in north central Alabama. All had driven within the past 3 months. Binocular visual acuity and contrast sensitivity were assessed. The Useful Field of View subtest 2 and Trails B assessed visual processing speed. Ophthalmological diagnoses for cataract, intraocular lens placement, glaucoma, diabetic retinopathy, age-related macular degeneration, and diabetic retinopathy were obtained through medical records from the most recent eye examination.
Ninety-two percent of drivers had visual acuity of 20/40 or better; only two drivers (0.1%) had acuity worse than 20/100. Ninety-three percent had normal contrast sensitivity (≥1.5). About 40% had slowed visual processing speed (44%, Useful Field of View; 38%, Trails B). The most common eye condition was cataract, with more than half having cataract in one or both eyes (56%); yet by the 80s and 90s, the prevalence was low, with most drivers having undergone cataract surgery and intraocular lens placement.
This population-based study suggests that serious impairment in central vision—visual acuity or contrast sensitivity—is rather uncommon in older drivers; however, slowed visual processing speed is common.
PMCID: PMC3623480  PMID: 22982690
Aging; Driving; Vision impairment; Eye disease
17.  Comparison of the Disease Activity Score using Erythrocyte Sedimentation Rate and C-reactive Protein in African-Americans with Rheumatoid Arthritis 
The Journal of rheumatology  2013;40(11):1812-1822.
The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arthritis (RA). Studies have reported discordance between DAS28 based on erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) in RA patients. However such comparison is lacking in African-Americans with RA.
This analysis included participants from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry which enrolls self-declared African-Americans with RA. Using tender and swollen joint counts separate ESR-based and CRP-based DAS28 scores (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4, which included the patient’s assessment of disease activity. The scores were compared using paired t-test, simple agreement and kappa, correlation coefficient and Bland-Altman plots.
Of the 233 included participants, 85% were women, mean age at enrollment was 52.6 years, and median disease duration at enrollment was 21 months. Mean DAS28-ESR3 was significantly higher than DAS28-CRP3 (4.8 vs. 3.9; p<0.001). Similarly, mean DAS28-ESR4 was significantly higher than DAS28-CRP4 (4.7 vs. 3.9; p<0.001). ESR-based DAS28 remained higher than CRP-based DAS28 even when stratified by age, sex, and disease duration. Overall agreement was not high between DAS28-ESR3 and DAS28-CRP3 (50%) or between DAS28-ESR4 and DAS28-CRP4 (59%). DAS28-CRP3 underestimated disease activity in 47% of the participants relative to DAS28-ESR3 and DAS28-CRP4 in 40% of the participants relative to DAS28-ESR4.
There was significant discordance between the ESR-based and CRP-based DAS28 which could impact clinical treatment decisions in African-Americans with RA.
PMCID: PMC3987124  PMID: 23950187
DAS28; Rheumatoid Arthritis; African-Americans
18.  Complementary and Alternative Medicine Use in African Americans With Rheumatoid Arthritis 
Arthritis care & research  2014;66(2):180-189.
Racial/ethnic differences with regard to complementary and alternative medicine (CAM) use have been reported in the US. However, specific details of CAM use by African Americans with rheumatoid arthritis (RA) are lacking.
Data were collected from African Americans with RA enrolled in a multicenter registry regarding the use of CAM, including food supplements, topical applications, activities, and alternative care providers. Factors associated with CAM use by sex and disease duration were assessed using t-test, Wilcoxon’s rank sum test, chi-square test, and logistic regression analyses.
Of the 855 participants, 85% were women and mean age at enrollment was 54 years. Overall, ever using any of the CAM treatments, activities, and providers was 95%, 98%, and 51%, respectively (median of 3 for number of treatments, median of 5 for activities, and median of 1 for providers). Those with longer disease duration (>2 years) were significantly more likely (odds ratio >2.0, P < 0.05) to use raisins soaked in vodka/gin, to take fish oils, or to drink alcoholic beverages for RA treatment than those with early disease. As compared to men, women were significantly (P < 0.05) more likely to pray/attend church, write in a journal, and use biofeedback, but were less likely to smoke tobacco or topically apply household oils for treatment of RA.
CAM use was highly prevalent in this cohort, even in individuals with early disease. Health care providers need to be aware of CAM use as some treatments may potentially have interactions with conventional medicines. This could be important within this cohort of African Americans, where racial disparities are known to affect access to conventional care.
PMCID: PMC3977347  PMID: 23983105
19.  A survey of Alabama eye care providers in 2010–2011 
BMC Ophthalmology  2014;14:44.
State level information regarding eye care resources can provide policy makers with valuable information about availability of eye care services. The current study surveyed ophthalmologists, optometrists and vision rehabilitation providers practicing in Alabama.
Three mutually exclusive provider groups were identified, i.e., all ophthalmologists, optometrists, and vision rehabilitation providers working in Alabama in 2010. Eligible providers were contacted in 2010 and 2011 and information was requested regarding provider demographics and training, practice type and service characteristics, and patient characteristics. Descriptive statistics (e.g., means, proportions) were used to characterize provider groups by their demographic and training characteristics, practice characteristics, services provided and patients or clients served. In addition, county level figures demonstrate the numbers and per capita ophthalmologists and optometrists.
Ophthalmologists were located in 24 of Alabama’s 67 counties, optometrists in 56, and 10 counties had neither an ophthalmologist nor an optometrist. Overall, 1,033 vision care professionals were identified as eligible to participate in the survey: 217 ophthalmologists, 638 optometrists, and 178 visual rehabilitation providers. Of those, 111 (51.2%) ophthalmologists, 246 (38.6%) optometrists, and 81 (45.5%) rehabilitation providers participated. Most participating ophthalmologists, optometrists, and vision rehabilitation providers identified themselves as non-Hispanic White. Ophthalmologists and optometrists estimated that 27% and 22%, respectively, of their patients had diabetes but that the proportion that adhered to eye care guidelines was 61% among ophthalmology patients and 53% among optometry patients.
A large number of Alabama communities are isolated from eye care services. Increased future demand for eye care is anticipated nationally given the aging of the population and decreasing numbers of providers; however, Alabama also has a high and growing prevalence of diabetes which will result in greater numbers at risk for diabetic retinopathy, glaucoma, and cataracts.
PMCID: PMC4233655  PMID: 24708636
Epidemiology; Survey; Vision care; Diabetic retinopathy
20.  Histologic Basis of Variations in Retinal Pigment Epithelium Autofluorescence in Eyes with Geographic Atrophy 
Ophthalmology  2013;120(4):821-828.
Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus auto-fluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression.
Experimental study.
Participants and Controls
Ten GA donor eyes (mean age ± standard deviation, 87.1±4.0 years) and 3 age-matched control eyes (mean age ± standard deviation, 84.0±7.2 years) without GA.
Ten–micrometer-thick sections were divided into zones of RPE morphologic features according to an 8-point scale. Any HAF excited by 488 nm light was imaged by laser confocal microscopy. The HAF intensity summed along vertical lines perpendicular to Bruch’s membrane at 0.2-μm intervals served as a surrogate for FAF. Intensity profiles in 151 zones were normalized to grade 0 at a standard reference location in each eye. Cross-sectional area, mean, and sum autofluorescence for individual RPE cells were measured (cellular autofluorescence [CAF]).
Main Outcome Measures
Statistically significant differences in intensity and localization of HAF and CAF at defined stages of RPE morphologic progression for GA and control eyes.
The RPE morphologic features were most abnormal (cell rounding, sloughing, and layering; grade 2) and HAF intensity profiles were highest and most variable immediately adjacent to atrophic areas. Peaks in HAF intensity frequently were associated with vertically superimposed cells. The HAF value that optimally separated reactive RPE was 0.66 standard deviations more than the mean for uninvolved RPE and was associated with a sensitivity of 75.8% and a specificity of 76.3%. When variable cell area was accounted for, neither mean nor sum CAF differed significantly among the RPE pathologic grades.
Areas with advanced RPE alterations are most likely to exhibit clinically recognizable patterns of elevated FAF around GA, but may not predict cells about to die, because of vertically superimposed cells and cellular fragments. These data do not support a role for lipofuscin-related cell death and call into question the rationale of treatments targeting lipofuscin.
PMCID: PMC3633595  PMID: 23357621
21.  Effect of an Eye Health Education Program on Older African Americans' Eye Care Utilization and Attitudes about Eye Care 
We examined the impact of an eye health education program for older African Americans on attitudes about eye care and utilization, using a randomized trial design in a community setting. Participants were older African Americans attending activities at senior centers. Ten centers were randomized to an eye health education (InCHARGE©) or social-contact control presentation. InCHARGE© addressed the importance of annual dilated comprehensive examination and strategies reducing barriers to care. The control presentation was on the importance of physical activity. Outcomes were attitudes about eye care through questionnaire 6 months post-event, and eye care utilization during 12 months post-event through medical record abstraction. At baseline > 80% participants in both arms said transportation and finding, communicating, and trusting a doctor were not problematic and agreed that yearly care was important. One-fourth said eye examination cost was problematic; one-half said spectacle cost was problematic. There were no group differences 6 months post-event. During 12 months pre-event, dilated exam rate was similar in the groups (38.3% InCHARGE©, 40.8% control), and unchanged during 12 months post-event. Results suggest less than half of older African Americans received annual dilated eye care. Group-administered eye health education did not increase this rate. Even before the program, they had positive attitudes about care, yet many cited examination and spectacle cost as problematic, which was not mitigated by health education. Evidence-based strategies in a community setting for increasing eye care utilization rate in older African Americans have yet to be identified. Policy changes may be more appropriate avenues for addressing cost.
PMCID: PMC3718503  PMID: 23862298
eye care utilization; eye health education; barriers to care
22.  Vision Impairment Among Older Adults Residing in Assisted Living 
Journal of aging and health  2013;25(2):364-378.
To examine rates of visual impairment of older adults in assisted living facilities (ALFs).
Vision screening events were held at 12 ALFs in Jefferson County, Alabama for residents ≥60 years of age. Visual acuity, cognitive status, and presence of eye conditions were assessed.
144 residents were screened. 67.8% failed distance screening, 70.9% failed near screening, and 89.3% failed contrast sensitivity screening. 40.4% of residents had cognitive impairment and 89% had a least one diagnosed eye condition. Visual acuities did not differ significantly between cognitive status groups or with greater numbers of eye conditions.
This study is the first to provide information about vision impairment in the assisted living population. Of those screened, 70% had visual acuity worse than 20/40 for distance or near vision, and 90% had impaired contrast sensitivity. Cognitive impairment accounted for a small percentage of the variance in near vision and contrast sensitivity.
PMCID: PMC3586252  PMID: 23338786
Visual impairment; assisted living facilities; older adults
23.  Comparison of diagnostic accuracy of HRT-II and HRT-3 to discriminate glaucomatous and non-glaucomatous eyes 
American journal of ophthalmology  2007;144(4):525-532.
To compare the diagnostic accuracy of the Moorfields Regression Analysis (MRA), parameters, and Glaucoma Probability Score (GPS) from Heidelberg Retinal Tomograph HRT-3 with MRA and parameters from HRT-II in discriminating glaucomatous and healthy eyes in subjects of African (AA) and European ancestry (EA).
case-control, institutional setting.
78 glaucoma patients (AA=44, EA=34) and 89 age-matched controls (AA=46, EA=33), defined by visual fields and self-reported race were included. Imaging was obtained with HRT-II and data were exported to a computer with the HRT-3 software using the same contour line. Area under Receiver-operating Characteristic [ROC] curves [AUC], sensitivity and specificity were evaluated for whole group, AA and EA separately. Mean disc area was compared between correctly and incorrectly diagnosed eyes by each technique.
Disc, cup and rim areas from HRT3 were lower than HRT-II (P<0.0001). AUC (sensitivity at 95%-specificity) was 0.85 (54%) for vertical cup-to-disc ratio (VCDR) HRT3, 0.84 (45%) for VCDR HRT-II, and 0.81 (44%) for GPS score at temporal sector. MRA-HRT3 showed greater sensitivity but lower specificity than HRT-II for whole group, AA and EA. GPS classification had lowest specificity. Glaucomatous eyes incorrectly classified by GPS had smaller mean disc area (P=0.0002); controls eyes incorrectly classified had greater mean disc area (P=0.015).
VCDR from HRT-3 showed higher sensitivity than HRT-II and GPS for the whole group, and AA and EA separately. Sensitivity of MRA improved in HRT-3 with some tradeoff in specificity compared to MRA of HRT-II. GPS yielded erroneous classification associated to optic disc size.
PMCID: PMC3928044  PMID: 17693382
24.  Prediction of Driving Safety in Individuals with Homonymous Hemianopia and Quadrantanopia from Clinical Neuroimaging 
Journal of Ophthalmology  2014;2014:754042.
Background. This study aimed to determine whether it is possible to predict driving safety of individuals with homonymous hemianopia or quadrantanopia based upon a clinical review of neuroimages that are routinely available in clinical practice. Methods. Two experienced neuroophthalmologists viewed a summary report of the CT/MRI scans of 16 participants with homonymous hemianopic or quadrantanopic field defects which indicated the site and extent of the lesion and they made predictions regarding whether participants would be safe/unsafe to drive. Driving safety was independently defined at the time of the study using state-recorded motor vehicle crashes (all crashes and at-fault) for the previous 5 years and ratings of driving safety determined through a standardized on-road driving assessment by a certified driving rehabilitation specialist. Results. The ability to predict driving safety was highly variable regardless of the driving safety measure, ranging from 31% to 63% (kappa levels ranged from −0.29 to 0.04). The level of agreement between the neuroophthalmologists was only fair (kappa = 0.28). Conclusions. Clinical evaluation of summary reports of currently available neuroimages by neuroophthalmologists is not predictive of driving safety. Future research should be directed at identifying and/or developing alternative tests or strategies to better enable clinicians to make these predictions.
PMCID: PMC3941145  PMID: 24683493
25.  Associations between Visual, Hearing, and Dual Sensory Impairments and History of Motor Vehicle Collision Involvement by Older Drivers 
To examine the association between visual and hearing impairment and motor vehicle collision (MVC) involvement in older drivers.
Retrospective cohort study.
North central Alabama
Population-based sample of 2,000 licensed-drivers, age 70 and older.
Visual acuity was measured using the Electronic Visual Acuity test. Contrast sensitivity was measured using the Pelli-Robson chart. Presence of subjective hearing loss and other health conditions were determined using a general health questionnaire. Information regarding MVCs for all participants spanning the five years prior to study enrollment was obtained from the Alabama Department of Public Safety.
Following adjustment for age, race, gender, number of miles driven, number of medical conditions, general cognitive status, and visual processing speed, older drivers having both visual acuity and hearing impairment (rate ratio RR 1.52, 95% confidence interval CI 1.01–2.30), contrast sensitivity impairment alone (RR 1.42, 95% CI 1.00–2.02), and both contrast sensitivity and hearing impairment (RR 2.41, 95% CI 1.62–3.57) had elevated MVC rates, compared to drivers with no visual or hearing impairments. Drivers with visual acuity loss alone or hearing loss alone did not have significantly different MVC rates when compared to the no impairment group after adjustment for multiple variables.
Older drivers with dual sensory impairment are at greater MVC risk than those with only a visual acuity or a hearing deficit alone. A combined screening approach of screening for both hearing impairment and visual impairment may be a useful tool to identify older drivers at risk for MVC involvement.
PMCID: PMC3573212  PMID: 23350867
driver safety; dual sensory impairment; vision impairment; hearing impairment

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