To evaluate the association between binocular visual field defects in drivers with glaucoma and risk of motor vehicle collision (MVC) involvement.
A retrospective cohort study was conducted on 438 drivers with glaucoma aged ≥ 55 years old using data from 1994 through 2000. Demographic, clinical, and driving characteristics were obtained from chart abstractions and patient survey. Binocular field measures were generated by combining data from the monocular (central 24° radius) fields whereby the binocular field measure was defined as the more sensitive point at each monocular field location. Measures included threshold (TH), total deviation (TD), and pattern deviation (PD); severe impairment in these measures was defined as falling into the worst quartile. MVC data was obtained from police records. Rate ratios (RR) and 95% confidence intervals (CI) were calculated.
Drivers with severely impaired PD measures were twice as likely to have an at-fault MVC compared to those not severely impaired (RR 2.13, 95% CI 1.21-3.75); those with severely impaired TH (RR 1.49, 95% CI 0.81-2.74) and TD (RR 1.50, 95% CI 0.82-2.74) also had an increased rate of at-fault MVCs, although these were not significant. When the binocular central visual field was stratified into 9 regions, drivers with impaired TH, TD, or PD had similarly elevated MVC rates in all regions compared to those not severely impaired, though not all reached statistical significance.
Based on clinical measures of visual field routinely used in the management of glaucoma, drivers with glaucoma with severe PD field defects in the binocular field have a higher rate of at-fault MVC compared to those with less impaired or unimpaired binocular visual fields.
The use of a non-mydriatic camera for retinal imaging combined with the remote evaluation of images at a telemedicine reading center has been advanced as a strategy for diabetic retinopathy (DR) screening, particularly among patients with diabetes from minority populations with low eye care utilization.
To examine the rate and types of DR identified through a telemedicine screening program using a non-mydriatic camera, as well as the rate of other ocular findings.
Four urban clinic or pharmacy settings in the United States serving predominantly minority and uninsured persons with diabetes.
Persons age ≥ 18 years old who have type 1 or 2 diabetes and present to the community-based settings.
Main Outcome Measure
Percentage of DR detection including type of DR, and percentage of detection of other ocular findings.
A total of 1,894 persons participated in the screening program across sites, with 21.7% having DR in at least one eye. The most common type of DR by far was background DR, which was present in 94.1% of all participants with DR. Almost half of those screened had ocular findings other than DR with 30% of other findings being cataract.
Conclusions and Relevance
In a DR telemedicine screening program in urban clinic/pharmacy settings in the US serving predominantly minority populations, 1 in 5 persons with diabetes screened positive for DR. The vast majority of DR was background indicating high public health potential for intervention in DR’s earliest phases when treatment can prevent vision loss. Other ocular conditions were detected at a high rate, a collateral benefit of DR screening programs that may be under appreciated.
Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs. rheumatic disease controls) and the association with SLE manifestations in an international multi-center study.
Information and blood samples were obtained in a cross-sectional study from patients with SLE (n=308) and other rheumatologic diseases (n=389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA.
Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR=2.7, 95% CI: 1.8-4, p<0.001). Anti-C1q was associated with proteinuria (OR=3.0, 95% CI: 1.7-5.1, p<0.001), red cell casts (OR=2.6, 95% CI: 1.2-5.4, p=0.015), anti-dsDNA (OR=3.4, 95% CI: 1.9-6.1, p<0.001) and anti-Smith (OR=2.8, 95% CI: 1.5-5.0, p=0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR=2.3, 95% CI: 1.3-4.2, p<0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR=14.9, 95% CI: 5.8-38.4, p<0.01).
Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.
To validate a model-driven method (RefMoB) of automatically describing the four outer retinal hyperreflective bands revealed by spectral-domain optical coherence tomography (SDOCT), for comparison with histology of normal macula; to report thickness and position of bands, particularly band 2 (ellipsoid zone [EZ], commonly called IS/OS).
Foveal and superior perifoveal scans of seven SDOCT volumes of five individuals aged 28 to 69 years with healthy maculas were used (seven eyes for validation, five eyes for measurement). RefMoB determines band thickness and position by a multistage procedure that models reflectivities as a summation of Gaussians. Band thickness and positions were compared with those obtained by manual evaluators for the same scans, and compared with an independent published histological dataset.
Agreement among manual evaluators was moderate. Relative to manual evaluation, RefMoB reported reduced thickness and vertical shifts in band positions in a band-specific manner for both simulated and empirical data. In foveal and perifoveal scans, band 1 was thick relative to the anatomical external limiting membrane, band 2 aligned with the outer one-third of the anatomical IS ellipsoid, and band 3 (IZ, interdigitation of retinal pigment epithelium and photoreceptors) was cleanly delineated.
RefMoB is suitable for automatic description of the location and thickness of the four outer retinal hyperreflective bands. Initial results suggest that band 2 aligns with the outer ellipsoid, thus supporting its recent designation as EZ. Automated and objective delineation of band 3 will help investigations of structural biomarkers of dark-adaptation changes in aging.
The four outer retinal hyperreflective bands of optical coherence tomography are modeled as Gaussian functions to accurately measure band thickness and position based on linear reflectivities. Comparison of these values with histology can refine knowledge of the subcellular sources of reflectivity.
optical coherence tomography; reflectivity; segmentation; retina; ellipsoid; interdigitation; photoreceptors; retinal pigment epithelium; age-related macular degeneration
Distracted driving contributes to a large proportion of motor vehicle crashes, yet little is known about the prevalence of distracted driving and the specific types of distracting behaviors. The objective of this study was to estimate the prevalence of driver distraction using a roadside observational study design.
A cross-sectional survey involving direct roadside observation was conducted at 11 selected intersections. Trained investigators observed a sample of passenger vehicles and recorded distraction-related behaviors, driver characteristics, and contextual factors such as vehicle speed and traffic flow.
Of the 3,265 drivers observed, the prevalence of distracted driving was 32.7%. Among those involved in a distracting activity, the most frequently observed distractions included interacting with another passenger (53.2%, where passengers were present), talking on the phone (31.4%), external-vehicle distractions (20.4%), and texting/dialing a phone (16.6%). The prevalence of talking on the phone was higher among females than males (38.6% vs. 24.3%), whereas external vehicle distractions were higher among males than females (25.8% vs. 24.3%). Drivers <30 years were observed being engaged in any distracting activity, interacting with other passengers and texting/dialing more frequently than drivers aged 30–50 and >50 years. Drivers were engaged in distracting behaviors more frequently when the car was stopped.
When using similar methodology, roadside observational studies generate comparable prevalence estimates of driver distraction as naturalistic driving studies. Driver distraction is a common problem among passenger vehicle drivers. Despite the increased awareness on the dangers of texting and cell phone use while driving, these specific activities were two of the most frequently observed distractions. There is a continued need for road safety education about the dangers of distracted driving, especially for younger drivers.
Distraction; driver; epidemiology; observational; prevalence; safety
Primary open angle glaucoma is a chronic, progressive eye disease that is the leading cause of blindness among African Americans. Glaucoma progresses more rapidly and appears about 10 years earlier in African Americans as compared to whites. African Americans are also less likely to receive comprehensive eye care when glaucoma could be detected before irreversible blindness. Screening and follow-up protocols for managing glaucoma recommended by eye-care professional organizations are often not followed by primary eye-care providers, both ophthalmologists and optometrists. There is a pressing need to improve both the accessibility and quality of glaucoma care for African Americans. Telemedicine may be an effective solution for improving management and diagnosis of glaucoma because it depends on ocular imaging and tests that can be electronically transmitted to remote reading centers where tertiary care specialists can examine the results. We describe the Eye Care Quality and Accessibility Improvement in the Community project (EQUALITY), set to evaluate a teleglaucoma program deployed in retail-based primary eye care practices serving communities with a large percentage of African Americans.
We conducted an observational, 1-year prospective study based in two Walmart Vision Centers in Alabama staffed by primary care optometrists. EQUALITY focuses on new or existing adult patients who are at-risk for glaucoma or already diagnosed with glaucoma. Patients receive dilated comprehensive examinations and diagnostic testing for glaucoma, followed by the optometrist’s diagnosis and a preliminary management plan. Results are transmitted to a glaucoma reading center where ophthalmologists who completed fellowship training in glaucoma review results and provide feedback to the optometrist, who manages the care of the patient. Patients also receive eye health education about glaucoma and comprehensive eye care. Research questions include diagnostic and management agreement between providers, the impact of eye health education on patients’ knowledge and adherence to follow-up and medication, patient satisfaction, program cost-effectiveness, and EQUALITY’s impact on Walmart pharmacy prescription rates.
As eye-care delivery systems in the US strive to improve quality while reducing costs, telemedicine programs including teleglaucoma initiatives such as EQUALITY could contribute toward reaching this goal, particularly among underserved populations at-risk for chronic blinding diseases.
Primary open angle glaucoma; Ocular hypertension; Glaucoma suspect; Health disparities; Telemedicine; Vision impairment; Eye care utilization; Eye health education; Spectral domain optical coherence tomography
Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC.
A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan-Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients.
62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p=0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7 kg/m2, p < 0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3 months, p=0.024) and OS (26.1 vs. 42.2 months, p=0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS.
EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.
Increasing rates of distraction-related motor vehicle collisions (MVCs) continue to raise concerns regarding driving safety. This study sought to evaluate a novel driving-related distraction, driving with a pet, as a risk factor for MVCs among older, community dwelling adults. Two thousand licensed drivers aged 70 and older were identified, of whom 691 reported pet ownership. Comparing pet owners who did and did not drive with their pets, neither overall MVC rates (rate ratio [RR] 0.97 95% confidence interval [CI] 0.75–1.26) nor at-fault MVC rates (RR 0.84 95% CI 0.57–1.24) were elevated. However, those who reported always driving with a pet in the vehicle had an elevated MVC rate (RR 1.89 95% CI 1.10–3.25), as compared to those who did not drive with a pet. The MVC rate was not increased for those reporting only sometimes or rarely driving with a pet in the vehicle. The current study demonstrates an increased risk of MVC involvement in those older drivers who always take a pet with them when they drive a vehicle. When confronted with an increased cognitive or physical workload while driving, elderly drivers in prior studies have exhibited slower cognitive performance and delayed response times in comparison to younger age groups. Further study of pet-related distracted driving behaviors among older drivers as well as younger populations with respect to driver safety and performance is warranted to appropriately inform the need for policy regulation on this issue.
We designed a visual field test focused on the field utilized while driving to examine associations between field impairment and motor vehicle collision involvement in 2000 drivers aged 70 years or older.
The “driving visual field test” involved measuring light sensitivity for 20 targets in each eye, extending 15° superiorly, 30° inferiorly, 60° temporally, and 30° nasally. The target locations were selected on the basis that they fell within the field region utilized when viewing through the windshield of a vehicle or viewing the dashboard while driving. Monocular fields were combined into a binocular field based on the more sensitive point from each eye. Severe impairment in the overall field or a region was defined as average sensitivity in the lowest quartile of sensitivity. At-fault collision involvement for 5 years prior to enrollment was obtained from state records. Poisson regression was used to calculate crude and adjusted rate ratios (RRs) examining the association between field impairment and at-fault collision involvement.
Drivers with severe binocular field impairment in the overall driving visual field had a 40% increased rate of at-fault collision involvement (RR, 1.40; 95% confidence interval [CI]: 1.07–1.83). Impairment in the lower and left fields was associated with elevated collision rates (RR, 1.40; 95% CI: 1.07–1.82 and RR, 1.49; 95% CI: 1.15–1.92, respectively), whereas impairment in the upper and right field regions was not.
Results suggest that older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.
Older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.
aging; driving; visual field
Little is known regarding eye care utilization among low income persons with diabetes, especially African Americans.
A retrospective cohort study with two-years of follow-up examined eye care utilization among adult diabetes patients seen in 2007 in the internal medicine clinic of a large, urban, county hospital that serves primarily low income, non-Hispanic African American patients. Patients with a history of retinopathy and macular edema or a current diagnosis indicating ophthalmic complications were excluded. Eye care utilization was defined dichotomously as whether or not patients had a visit to the eye clinic for any eye care examination or procedure. We estimated crude and adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for the association between eye care utilization and selected clinical and demographic characteristics.
There were 867 patients with diabetes identified: 61.9% women, 76.2% non-Hispanic African American, 61.3% indigent, and average age 51.8 years. Eye care utilization was 33.2% within one-year and 45.0% within two-years. For patients 19–39 years of age compared to those 65+ years, significantly decreased eye care utilization was observed within one-year (aRR=0.48, 95% CI 0.27–0.84) and within two-years (aRR=0.61, 95% CI 0.38–0.99).
Overall eye care utilization was low. Additional education efforts to increase the perception of need among urban minority populations may be enhanced if focused on younger people with diabetes.
diabetes; retinopathy; epidemiology; eye exam
We examined the feasibility and efficacy of using a non-mydriatic camera to screen for diabetic retinopathy (DR) among youth with type 1 or type 2 diabetes seen in a pediatric endocrinology clinic serving Alabama, the state that has the highest diabetes rate in the United States.
236 youths with type 1 or type 2 diabetes were screened for DR using a non-mydriatic camera. Visual acuity was also assessed. A questionnaire asked parents about diabetes and eye care history.
Mean duration since diabetes diagnosis was 5.5 years. 66 % reported receiving an eye examination within the previous year. 97.5 % had images that were gradable. DR was detected in 3.8 % of participants. 9.1 % were visually impaired.
Use of a non-mydriatic fundus camera is feasible and efficacious for DR screening in youth with diabetes. DR screening at routine endocrinology visits may be beneficial in managing youth with diabetes and preventing irreversible vision loss, particularly for those in regions where diabetes rates are high.
Diabetes mellitus; Diabetes complications; Diabetic retinopathy; Pediatrics; Visual acuity
To investigate the ocular neovascularization (ONV) rate in eyes with a branch retinal artery occlusion (BRAO) or a central retinal artery occlusion (CRAO), and to study factors that may influence the ONV rate secondary to CRAO.
This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs) who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development.
Twelve (14.5%) of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7%) had iris neovascularization, ten of 12 eyes (83.3%) had neovascular glaucoma, and two of 12 eyes (16.7%) had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0%) of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8) (P=0.02).
ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV.
neovascularization; neovascular glaucoma; retinal artery occlusion; central retinal artery occlusion; branch retinal artery occlusion; diabetes mellitus
To examine the relationship between vision impairment and driving exposure (amount of driving one does) in a population-based sample of older drivers, and to examine to what extent cognitive status impacts this relationship.
Enrollees consisted of a population-based sample of older adults from Alabama who were ≥ 70 years old, held a current driver’s license, and had driven within the last 3 months. Three aspects of visual function were measured under binocular conditions – habitual distance visual acuity, contrast sensitivity, and visual processing speed. General cognitive status was assessed with the Mini-mental status examination. Driving exposure was estimated by the Driving Habits Questionnaire that asked about the number of miles, places, trips and days driven per week.
Drivers with impaired contrast sensitivity exhibited reduced annual mileage, and a decreased number of places and trips driven per week compared to those with normal contrast sensitivity, even after adjustment for other factors. Slowed visual processing speed was associated with reduced number of days driven per week after adjustment. Visual acuity deficit was not associated with changes in driving exposure. Cognitive status did not impact any of the associations between vision impairment and driving exposure.
Older drivers with contrast sensitivity impairment exhibit reduced driving exposure in terms of number of trips and places they drive per week, as well as decreased annual mileage. These apparent self-regulatory practices should be viewed as adaptive since contrast sensitivity impairment elevates motor vehicle collision (MVC) risk and reduction in driving exposure can reduce MVC risk.
driving; aging; vision impairment; visual acuity; contrast sensitivity; visual processing speed
To investigate whether the FcγRIIIa-66R/H/L polymorphism influences net effective receptor function and to assess if the FCGR3A combined genotypes formed by FcγRIIIa-66R/H/L and FcγRIIIa-176F/V as well as copy number variation (CNV) confer risk for development of SLE and lupus nephritis.
FcγRIIIa variants, expressed on A20 IIA1.6 cells, were used in flow cytometry-based human IgG binding assays. FCGR3A SNP and CNV genotypes were determined by Pyrosequencing methodology in a cohort of 1728 SLE patients and 2404 healthy controls.
The FcγRIIIa-66L/H/R (rs10127939) polymorphism influences ligand binding capacity in the context of the FcγRIIIa-176V (rs396991) allele. The low binding FcγRIIIa-176F allele was associated with SLE nephritis (p = 0.0609) in African Americans but not in European Americans (p > 0.10). Nephritis among African American SLE subjects was associated with FcγRIIIa low binding haplotypes containing the 66R/H/L and 176F variants (p = 0.03) and with low binding genotype combinations (p = 0.002). No association was observed in European American SLE patients. The distribution of FCGR3A CNV was not significantly different between controls and SLE patients with or without nephritis.
FcγRIIIa-66R/H/L influences ligand binding. The low binding haplotypes formed by 66R/H/L and 176F confer enhanced risk for lupus nephritis in African Americans. FCGR3A CNVs are not associated with SLE or SLE nephritis in either African Americans or European Americans.
Rett Syndrome (RTT), a neurodevelopmental disorder that primarily affects girls, is characterized by a period of apparently normal development until 6–18 months of age, when motor and communication abilities regress. More than 95% of people with RTT have mutations in Methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. Surprisingly, although the disorder is caused by mutations in a single gene, disease severity in affected individuals can be quite variable. To explore the source of this phenotypic variability, we propose that specific MECP2 mutations lead to different degrees of disease severity. Using a database of 1052 participants assessed over 4940 unique visits, the largest cohort of both typical and atypical RTT patients studied to date, we examined the relationship between MECP2 mutation status and measures of growth, motor coordination, communicative abilities, respiratory function, autonomic symptoms, scoliosis, and seizures over time. In general agreement with previous studies, we found that particular mutations, such as p.Arg133Cys, p.Arg294X, p.Arg306Cys, 3′ Truncations, and Other Point Mutations, were relatively less severe in both typical and atypical RTT. In contrast, p.Arg106Trp, p.Arg168X, p.Arg255X, p.Arg270X, Splice Sites, Large Deletions, Insertions, and Deletions were significantly more severe. We also demonstrated that, for most mutation types, clinical severity increases with age. Furthermore, of the clinical features of RTT, ambulation, hand use, and age at onset of stereotypies are strongly linked to overall disease severity. Thus, we have confirmed that MECP2 mutation type is a strong predictor of disease severity. However, clinical severity continues to become progressively worse with advancing age regardless of initial severity. These findings will allow clinicians and families to anticipate and prepare better for the needs of individuals with RTT.
genotype-phenotype; MeCP2; Rett syndrome; RTT
Recent research has suggested that driver distraction is a major cause of driving performance impairment and motor vehicle collisions. Research on the topic has focused on passenger vehicles, with studies suggesting that drivers may be distracted nearly 33% of the time spent driving. To date, no study has examined the prevalence of distraction specifically among public transit bus drivers.
Over a three-month period, trained investigators observed and recorded distraction behaviors of bus drivers. Distraction prevalence was compared by route characteristics (e.g., geographic area, travel speed) using chi-square test. A general estimating equation logistic regression was used to estimate p-values for distraction prevalence by driver demographics.
Overall, there was a 39% prevalence of distraction. The most prevalent distractions were due to interactions with another passenger. Distractions were more prevalent among drivers <30 years of age or ≥50 years of age, on city streets or highways (relative to residential streets), and when there were more than 20 passengers. Distractions were the least prevalent in suburban areas, with the highest prevalence observed in city centers and rural areas.
Driver distraction is a common problem for public transit bus drivers, mainly due to other passengers. Drivers should be educated on the hazards of distracted driving and on ways to avoid distraction.
Bus; driver; distraction; prevalence; public transit
To examine the relationship between frequent falls in older drivers and motor vehicle collision (MVC) involvement.
North central Alabama.
Population-based sample of 2,000 licensed drivers aged 70 and older.
Self-reported history of falling two or more times in the prior year was the main predictor. Outcomes were any MVC or at-fault MVC in the prior year.
Approximately 9% of older drivers reported having fallen two or more times in the prior year. Logistic regression models indicated that frequent falling was associated with having any MVC (crude odds ratio (OR) = 1.53, 95% confidence interval (CI) = 0.77–3.02) and an at-fault MVC (OR = 2.21, 95% CI = 0.97–5.06). Adjustment for the potentially confounding effects of demographic, health, visual, and driving characteristics did not meaningfully affect the association with any MVC, whereas the association with at-fault MVC was weakened (adjusted OR = 2.03, 95% CI = 0.84–4.90).
Frequent falling was associated with at-fault MVC involvement of older drivers, especially whites. History of falling can be used to identify individuals at risk of MVC involvement and to begin a dialogue about driver safety. J Am Geriatr Soc 2013.
falls; aging; driver safety
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.
aging; dark adaptation; rod function; age-related macular degeneration
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.
retinal pigment epithelium; autofluorescence; photoreceptor; lipofuscin; cytoskeleton
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.
cup-to-disc ratio; HRT II; Stratus OCT; stereoscopic optic nerve head photographs
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.
Adolescents; Children; Chronic pain; Disability; Functional capacity; Pain intensity; Parent-child; Pediatrics
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.
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.
Motor Vehicle Collision; Cataract Surgery; Monte Carlo Simulation; Elderly; Cost Effectiveness; Medicare; Insurance
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.