Real-World Performance Benchmarks in the Reading Ability of Prescription Drug Labels by Community-Dwelling Older Adults.

BACKGROUND: Despite known recommendations regarding standards for print size and the intuitive importance of vision in reading prescription labels, the predictive nature of vision and prescription label readability remains largely undefined. Furthermore, while the importance of vision is recognized, various demographic factors associated with the ability to read prescription labels have not been fully elucidated. OBJECTIVE: Describe relationships between visual acuity, point size, and readability of prescription labels and provide insight into demographic factors associated with prescription label readability. METHODS: Cross-sectional examination of prescription label readability by older, community-dwelling adults. Subjects were evaluated as to demographics, visual acuity, and ability to read test instruments consisting of unaltered prescription label features of five medications dispensed by community pharmacies and two drug samples. Descriptive statistics in conjunction with a logit predictive model were employed for data analysis. RESULTS: Instructions for medication use were most recognizable, identified and correctly read by 95.60% of the study cohort while directions for the use of drug samples were lowest (34.91%). Among prescription label features, auxiliary labels consistently demonstrated poor readability. Level of visual acuity was statistically related to the ability to read prescription labels while identifying prescription label components increased proportionally with point size. Race, gender, and history of a recent eye examination were statistically significant predictors of prescription label reading ability. Visual acuity alone was found to explain approximately 26% of the variablity in ability to read Rx labels. CONCLUSION: Visual acuity is predictive of the ability to access Rx label information and should be considered a modifiable variable for improving prescription label reading ability amenable by appropriate eye care and spectacle correction.

Effect of Age and Viscosity on Duration of Corneal Anesthesia with Topical 2% Lidocaine Administration.

Purpose: Formulation viscosity and patient-specific parameters such as age are important considerations in achieving patient comfort for prolonged anterior segment surgical procedures. In this study, we report pharmacodynamic and pharmacokinetic parameters of topical 2% lidocaine anesthetic decay based on formulation viscosity and subject age. Methods: Extemporaneous 2% lidocaine solution was compounded with varying percentages of carboxymethylcellulose (CMC) to adjust product viscosity. Juvenile and adult New Zealand White rabbits were utilized as a model for lidocaine-induced corneal anesthesia analysis. Following application of 20 µL in 1 eye of each animal, corneal sensitivity was measured using a Cochet-Bonnet esthesiometer at baseline and at 1-min intervals until recovery to baseline. Subsequent to washout period, the experiment was repeated for 3 replicate experiments. Results: A one-phase exponential decay model was utilized to describe rate of anesthesia decay. Bioavailability increased in a manner disproportionate to both tear film concentration and solution viscosity. In adult animals, half-life of anesthetic decay was found to range from 6.03 min with 2% lidocaine in 0.5% CMC to 9.45 min with 2% lidocaine in 1.5% CMC. In juveniles, half-life was found to be 4.46 and 3.58 min for 2% lidocaine in 1.5% CMC and commercial 2% lidocaine gel, respectively. Conclusions: Decay parameters of lidocaine-induced corneal anesthesia appear disparate from viscosity. It is postulated that viscosity-related increase in corneal contact time through reduced drainage plays a critical role in increasing bioavailability of topical anesthetics in our experimental findings, although nonlinear in character. Age is found to be an important mediator of lidocaine-induced corneal anesthesia.

Hierarchical data visualization of experimental erythrocyte aggregation employing cross correlation and optical flow applications.

Appraisal of microvascular erythrocyte velocity as well as aggregation are critical features of hemorheological assessment. Examination of erythrocyte velocity-aggregate characteristics is critical in assessing disorders associated with coagulopathy. Microvascular erythrocyte velocity can be assessed using various methodologic approaches; however, the shared assessment of erythrocyte velocity and aggregation has not been well described. The purpose of this study therefore is to examine three independent erythrocyte assessment strategies with and without experimentally induced aggregation in order to elucidate appropriate analytic strategy for combined velocity/aggregation assessment applicable to in-vivo capillaroscopy. We employed a hierarchical microfluidic model combined with Bland-Altman analysis to examine agreement between three methodologies to assess erythrocyte velocity appropriate for interpretation of cinematography of in-vivo microvascular hemorheology. We utilized optical and manual techniques as well as a technique which we term transversal temporal cross-correlation (TTC) to observe and measure both erythrocyte velocity and aggregation. In general, optical, manual and TTC agree in estimation of velocity at relatively low flow rate, however with an increase in infusion rate the optical flow method yielded the velocity estimates that were lower than the TTC and manual velocity estimates. We suggest that this difference was due to the fact that slower moving particles close to the channel wall were better illuminated than faster particles deeper in the channel which affected the optical flow analysis. Combined velocity/aggregation appraisal using TTC provides an efficient approach for estimating erythrocyte aggregation appropriate for in-vivo applications. We demonstrated that the optical flow and TTC analyses can be used to estimate erythrocyte velocity and aggregation both in ex-vivo microfluidics laboratory experiments as well as in-vivo recordings. The simplicity of TTC method may be advantageous for developing velocity estimate methods to be used in the clinic. The trade-off is that TTC estimation cannot capture features of the flow based on optical flow analysis of individually tracked particles.

A meta-analysis of variability in conjunctival microvascular hemorheology metrics.

Conjunctival hemorheology has been used analytically to assess qualities of blood flow associated with various forms of cardiovascular disorders including diabetes mellitus, stroke, and sickle cell disease. Although conjunctival axial red blood cell velocity (Vax) has been demonstrated in varying disease states, benchmark measures of Vax are not well-defined. Due to various methodologic differences in assessment of Vax, interstudy consistency of hemorheological metrics is susceptible to both systematic and random error. Our study examines interstudy heterogeneity of Vax as measured in the conjunctival microvasculature of healthy subjects and assesses the overall perturbation of Vax based on disease state. Furthermore, our study aims to establish a potential range of normative Vax by comparing inter-study measurements in healthy patients. The most widely employed analytic approach to assess Vax was space-time analysis (n = 30). Using a meta-analytic approach, the prediction interval for Vax in healthy subjects among 20 studies ranged from 0.32-2.60 mm/s with a combined effect size of 0.52 ± 0.03 (CI: 0.46-0.59) mm/s. Inter-study comparison of Vax in healthy patients showed a high degree of variability (I2: 98.96%), due to studies with low measurement precision and/or dissimilar analytic methodology. Neither age nor diameter was a clinically significant moderator of Vax measurements in healthy patients. The combined effect size, defined as the composite Hedge's g of studies comparing healthy and disease state mean Vax, was 0.21 ± 0.13. High heterogeneity (I2: 80.48%) was observed in studies analyzing the difference between mean Vax in healthy and disease state patients. This heterogeneity was also observed when the difference in mean Vax between healthy and disease state patients was assessed in subgroups based on disease condition (I2: vascular disease 33%, sickle cell disease 62.22%, other 83.43%). Age was found to be a significant moderator (p = 0.048, ß = -0.40) of Hedge's g while diameter was not. No significant publication bias was observed in studies presenting healthy patient Vax or in studies comparing Vax between healthy and disease state patients. In summary, although homogeneity can be seen in healthy group Vax measurements, a high degree of statistical heterogeneity is found in Vax assessment comparing healthy and disease conditions that is not fully explained by methodologic variability.

Variable abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson's disease (PD) and parkinsonism features.

OBJECTIVES: Ascertain and quantify abnormality of the melanopsin-derived portion of the pupillary light reflex (PLR) in patients with Parkinson's disease (PD) and parkinsonism features based on a statistical predictive modeling strategy for PLR classification. METHODS: Exploratory cohort analysis of pupillary kinetics in non-disease controls, PD subjects, and subjects with parkinsonism features using chromatic pupillometry. Receiver operating characteristic (ROC) curve interpretation of pupillary changes consistent with abnormality of intrinsically photosensitive retinal ganglion cells (ipRGCs) was employed using a thresholding algorithm to discriminate pupillary abnormality between study groups. RESULTS: Twenty-eight subjects were enrolled, including 17 PD subjects (age range 64-85, mean 70.65) and nine controls (age range 48-95, mean 63.89). Two subjects were described as demonstrating parkinsonism symptoms due to presumed Lewy body dementia and motor system atrophy (MSA) respectively. On aggregate analysis, PD subjects demonstrated abnormal but variable pupillary dynamics suggestive of ipRGC abnormality. Subjects with parkinsonism features did not demonstrate pupillary changes consistent with ipRGC abnormality. There was no relationship between levodopa equivalent dosage or PD severity and ipRGC abnormality. The pupillary test sensitivity in predicting PD was 0.75 and likelihood ratio was 1.2. CONCLUSIONS: ipRGC deficit is demonstrated in PD subjects; however, the degree and constancy of abnormality appear variable.

Study of ultrasound thrombolysis using acoustic bubbles in a microfluidic device.

Thrombosis is a common medical entity associated with many forms of cardiovascular disease including myocardial infarction and stroke. Recently, ultrasound thrombolysis has emerged as a promising technique for thrombosis treatment by delivering acoustic waves onto blood clots. In this study, an ultrasound thrombolysis method is presented using an acoustic bubble-based microfluidic device. With acoustic actuation, microstreaming flow is created in the microchannel by oscillating bubbles, breaking up the blood clots in blood samples in a few milliseconds. In a low-frequency field, the effects of bubble size on microstreaming patterns and thrombolysis have been experimentally studied. Using image processing techniques, we have quantitatively investigated the relationship between the input signal and the thrombolysis performance. Additionally, the viability test proved that there are no significant detrimental effects on the blood cells after acoustic actuation. This acoustic bubble-based microfluidic device is demonstrated to be a promising platform for quantitative analysis of ultrasound thrombolysis. It opens up possibilities for future development of ultrasound thrombolysis devices for the diagnosis and treatment of heart diseases.

Detection of Parkinson's Disease Through Automated Pupil Tracking of the Post-illumination Pupillary Response.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, but it is often diagnosed after the majority of dopaminergic cells are already damaged. It is critical to develop biomarkers to identify the disease as early as possible for early intervention. PD patients appear to have an altered pupillary response consistent with an abnormality in photoreceptive retinal ganglion cells. Tracking the pupil size manually is a tedious process and offline automated systems can be prone to errors that may require intervention; for this reason in this work we describe a system for pupil size estimation with a user interface to allow rapid adjustment of parameters and extraction of pupil parameters of interest for the present study. We implemented a user-friendly system designed for clinicians to automate the process of tracking the pupil diameter to measure the post-illumination pupillary response (PIPR), permit manual corrections when needed, and continue automation after correction. Tracking was automated using a Kalman filter estimating the pupil center and diameter over time. The resulting system was tested on a PD classification task in which PD subjects are known to have similar responses for two wavelengths of light. The pupillary response is measured in the contralateral eye to two different light stimuli (470 and 610 nm) for 19 PD and 10 control subjects. The measured Net PIPR indicating different responsiveness to the wavelengths was 0.13 mm for PD subjects and 0.61 mm for control subjects, demonstrating a highly significant difference (p < 0.001). Net PIPR has the potential to be a biomarker for PD, suggesting further study to determine clinical validity.

Innovations in topical ocular corticosteroid therapy for the management of postoperative ocular inflammation and pain.

Topical ophthalmic corticosteroids are of clinical benefit in the management of pain and inflammation after ocular surgery; however, their use can be associated with class-associated adverse events (AEs) and limited bioavailability. Selection of an appropriate topical corticosteroid depends on drug-specific variables such as AE profile, efficacy, potency, dosing, patient-specific administration needs, and formulation properties aimed at minimizing precorneal drug loss, increasing ocular surface drug residence time, and maximizing drug delivery to the anterior tissues. Recently, strategies for improving ocular penetration of ophthalmic formulations have included use of mucoadhesive formulations (ie, polycarbophil-containing gels) and drug particle size reduction, enabling faster drug dissolution and therefore increased bioavailability and penetration. Loteprednol etabonate (LE) is a carbon-20 ester corticosteroid developed through retrometabolic drug design with potent anti-inflammatory effects and a reduced propensity for eliciting corticosteroid class AEs. This drug has been formulated for topical ophthalmic use after surgery as 0.5% and 1% suspensions, a 0.5% ointment, and a 0.5% gel. Preclinical and clinical data for a new 0.38% LE gel will be reviewed demonstrating that reducing the drug particle size to the nanometer range in diameter provides effective ocular tissue penetration and resolution of pain and inflammation despite a reduced drug concentration (0.38%) and dosing frequency.

Dosage considerations in the combined use of ocular-specific vitamins and nutrients and multivitamin products: A systemic review and analysis.

OBJECTIVES: To provide guidance for safe and appropriate vitamin and mineral supplementation regimens for patients who use vitamins marketed for ocular use concurrently with general-purpose multivitamin (MVI) supplementation. DATA SOURCES: Primary and tertiary evidence was compiled from secondary literature reference databases. STUDY SELECTION: Dosage exposure with the use of supplements marketed for the prevention of ocular disease, including those recommended by the Age-Related Eye Disease Studies (AREDS), when used in combination with conventional MVI/nutrient products was determined. An analysis of the data was performed to suggest appropriate supplement recommendations. DATA EXTRACTION: Combined dosages for single and duplicate ingredients found in ocular supplements and select MVI/nutrient supplements were compared with U.S. Food and Drug Administration--recommended daily value intake levels and the National Academy of Medicine recommendations on vitamin and nutrient tolerable upper intake levels (TUILs). RESULTS: With the exception of copper, all studied product components that conformed to AREDS guidelines for vitamin and nutrient levels far exceeded U.S. Food and Drug Administration--recommended daily value intake level limits. Furthermore, vitamin A and zinc exceeded the National Academies of Medicine TUIL when a multivitamin product was combined with an ocular-specific vitamin or nutrient that conformed with AREDS-recommended dosage levels. Several products marketed specifically for ocular use failed to provide AREDS-recommended vitamin or nutrient levels even when combined with MVI products. CONCLUSION: With the exception of vitamin A and zinc, the addition of typical multivitamin preparations to AREDS-recommended vitamin and nutrient regimens do not result in vitamin and mineral dosages that exceed TUIL as outlined by the National Academy of Medicine. However, combined AREDS and MVI regimens can create a substantial vitamin or mineral burden that is not appropriate for all older adult populations, particularly those with comorbidities, contributing to susceptibility of component toxicity.

A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.

Serum vitamin A, zinc and visual function in children with moderate to severe persistent asthma.

Background: Asthma is a common childhood disorder with complex pathobiologic components that may include aspects of nutritional deficit. The contribution of vitamin deficiency, specifically vitamin A, as part of the disease complex has not been well studied, particularly among at risk children. In this study, we examined the prevalence of vitamin A as well as zinc deficiency in conjunction with visual function among an urban pediatric population sample with moderate-severe persistent asthma. Methods: A cross-sectional case-control assessment of serum vitamin A, zinc and visual function among urban children with and without asthma was undertaken. Inclusion criteria involved (1) well-controlled pediatric asthmatic patients between the ages of 8-18 with corrected vision of at least 20/25 in each eye and (2) chronic use of a combination beta agonist-steroid inhaler. Visual function was assessed by Snellen visual acuity and Peli Robson contrast sensitivity assessment. Results: Overall, 24 patients were enrolled for study with body mass index and age matched between asthmatic and control groups. Median serum vitamin A and zinc levels among control subjects was statistically higher compared to asthmatics (p = 0.0303 and p = 0.0111, respectively). Based on age-based reference levels there was no evidence of vitamin A or zinc deficiency among asthmatics or controls. Serum vitamin A and zinc were found to directly correlate with body mass index (p = 0.0074 and p = 0.0474, respectively), but not age or measures of visual function. Contrast sensitivity was however significantly reduced among asthmatic subjects (p = 0.0003). Conclusions: Children with chronic asthma demonstrate reduced levels of vitamin A and zinc that may be related to disease pathobiology however, evidence of frank zinc or vitamin A deficiency was not demonstrated. Reduced contrast sensitivity found in the asthmatic group appears unrelated to serum vitamin A and/or zinc levels.

Exponential Decay Metrics of Topical Tetracaine Hydrochloride Administration Describe Corneal Anesthesia Properties Mechanistically.

PURPOSE: To identify pharmacodynamic (PD) and pharmacokinetic (PK) metrics that aid in mechanistic understanding of dosage considerations for prolonged corneal anesthesia. METHODS: A rabbit model using 0.5% tetracaine hydrochloride was used to induce corneal anesthesia in conjunction with Cochet-Bonnet anesthesiometry. Metrics were derived describing PD-PK parameters of the time-dependent domain of recovery in corneal sensitivity. Curve fitting used a 1-phase exponential dissociation paradigm assuming a 1-compartment PK model. Derivation of metrics including half-life and mean ligand residence time, tau (τ), was predicted by nonlinear regression. Bioavailability was determined by area under the curve of the dose-response relationship with varying drop volumes. RESULTS: Maximal corneal anesthesia maintained a plateau with a recovery inflection at the approximate time of predicted corneal drug half-life. PDs of recovery of corneal anesthesia were consistent with a first-order drug elimination rate. The mean ligand residence time (tau, τ) was 41.7 minutes, and half-life was 28.89 minutes. The mean estimated corneal elimination rate constant (ke) was 0.02402 minute. Duration of corneal anesthesia ranged from 55 to 58 minutes. There was no difference in time domain PD area under the curve between drop volumes. CONCLUSIONS: Use of a small drop volume of a topical anesthetic (as low as 11 µL) is bioequivalent to conventional drop size and seems to optimize dosing regiments with a little effect on ke. Prolongation of corneal anesthesia may therefore be best achieved with administration of small drop volumes at time intervals corresponding to the half-life of drug decay from the corneal compartment.

Conjunctival microvascular hemodynamics following vaso-occlusive crisis in sickle cell disease.

Painful vaso-occlusive crisis (VOC) is the clinical hallmark of sickle cell disease (SCD). Microcirculatory hemodynamic changes following painful VOC may be indicative of future development of VOC events in subjects with SCD. The purpose of the present study was to determine alterations in conjunctival microvascular hemodynamics during non-crisis state in SCD subjects with a history of VOC. Conjunctival microcirculation imaging was performed to measure conjunctival diameter (D) and axial blood velocity (V) in 10 control and 30 SCD subjects. SCD subjects were categorized into two groups based on their history of VOC within a 2-year period before imaging (with or without VOC-H) and also based on whether there was progression in the rate of VOCs during a 2-year period following imaging as compared to before imaging (with or without VOC-P). Conjunctival V was significantly higher in SCD subjects with VOC-H than in both control subjects and SCD subjects without VOC-H (P≤0.03). Conjunctival V was also significantly higher in SCD subjects with VOC-P compared with control subjects and SCD subjects without VOC-P (P≤0.03). Assessment of the conjunctival microcirculation may be useful for understanding hemodynamic changes that lead to VOC events in SCD subjects.

Changes in Conjunctival Hemodynamics Predict Albuminuria in Sickle Cell Nephropathy.

BACKGROUND: Albuminuria is an early manifestation of deterioration in renal function in subjects with sickle cell disease (SCD). Hyperfiltration may be an early mechanism for kidney damage in SCD. The purpose of the current study was to determine the association between conjunctival hemodynamics and albuminuria in SCD subjects with preserved glomerular filtration rate. METHODS: Conjunctival microcirculation imaging was performed to measure conjunctival diameter and axial blood velocity (V) in 35 SCD and 10 healthy control subjects. Albuminuria, defined as albumin excretion ratio (AER), was obtained from the medical charts. Based on the 95% CI of conjunctival V in control subjects (0.40-0.60 mm/s), SCD subjects were allocated to 3 groups: V1 <0.40 mm/s (n = 7), V2 of 0.40-0.60 mm/s (n = 18) and V3 ≥0.60 mm/s (n = 10). RESULTS: Mean log(AER) measurements in the V1, V2 and V3 groups were 1.08 ± 0.67, 1.39 ± 0.59 and 2.00 ± 0.91 mg/g creatinine, respectively, and followed a positive linear trend from the V1 to V3 groups (p = 0.01). By multivariate linear regression analysis, conjunctival V significantly correlated with albuminuria (p = 0.01) independent of age, blood pressure, α-thalassemia, hematocrit, white blood cell count and lactate dehydrogenase concentration. CONCLUSIONS: Increased conjunctival V is associated with albuminuria in SCD subjects. Assessment of conjunctival microvascular hemodynamics may improve our understanding of the pathophysiology and clinical management of sickle cell nephropathy.

Conjunctival microvascular haemodynamics in sickle cell retinopathy.

PURPOSE: To determine alterations in bulbar conjunctival microvascular haemodynamics in sickle cell retinopathy (SCR) subjects with focal macular thinning (FMT). METHODS: Conjunctival microcirculation imaging and spectral domain optical coherence tomography (SD-OCT) were performed in 22 subjects (eyes) diagnosed with SCR. Based on evaluation of SD-OCT retinal thickness maps, eyes were assigned to one of the two groups: with or without FMT. Conjunctival venular diameter and axial blood velocity were measured in multiple venules in each eye by customized image analysis algorithms. Measurements were then categorized into two vessel size groups (vessel size 1 and 2) and compared between FMT groups. A Pearson correlation coefficient was computed to assess the relationship between retinal thickness and axial blood velocity. RESULTS: Mean age, haematocrit, sickle cell haemoglobin type and median retinopathy score were not significantly different between the two groups (p ≥ 0.1). Retinal thickness in parafoveal and perifoveal temporal subfields was significantly lower in eyes with FMT as compared to eyes without FMT (p ≤ 0.04). There was a significant effect of FMT on axial blood velocity (p = 0.04), while the effect of vessel size was not significant (p = 0.4). In vessel size 1, axial blood velocity was lower in eyes with FMT than in eyes without FMT (p = 0.03), while in vessel size 2, there was no statistically significant difference between FMT groups (p = 0.1). In vessel size 1, there was a significant positive correlation between axial blood velocity and retinal thickness in the perifoveal (r = 0.48, p = 0.02) and parafoveal (r = 0.43, p = 0.04) temporal subfields. CONCLUSION: Conjunctival axial blood velocity in small venules is reduced in SCR subjects with focal macular thinning.