PRESERFLO™ Microshunt: 1-Year Results of a 25-Gauge vs. 27-Gauge Needle Tract.

Background: The purpose of this study was to evaluate the effectiveness and safety of the PreserFlo™ microshunt (PMS) using a 25-Gauge vs. 27-Gauge needle tract. Methods: This is a prospective postoperative examination of 60 glaucoma eyes that received a PMS. The main outcome measures were intraocular pressure (IOP), glaucoma drug score (GDS), Kaplan-Meier success rates, complications, and secondary intervention rates. Two subgroups were formed for data comparison: 27-Gauge (27G), and 25-Gauge (25G). Success was defined as IOP < 18 mmHg together with ≥20% IOP reduction with medication allowed (qualified success = QS18) or not (full success = FS18). Results: IOP and GDS were reduced from baseline to the 1-year study visit as follows: All eyes from 23.4 ± 8.6 mmHg (3.1 ± 0.9) to 15.1 ± 5.9 mmHg (0.8 ± 1.1); 25G from 24.2 ± 7.3 mmHg (3.0 ± 0.8) to 12.7 ± 2.7 mmHg (0.5 ± 0.8); and 27G from 23.1 ± 9.2 mmHg (3.1 ± 1.0) to 16.2 ± 6.7 mmHg (0.9 ± 1.2). IOP at one year was lower in the 25G group compared to the 27G group (p = 0.035). Bleb needling was required in eight (13.3%) eyes and open bleb revisions in three (5.0%). Transient hypotony occurred in 21% and choroidal effusion in 8% of all eyes. Choroidal effusions were more frequent in the 25G group (21%) compared to the 27G group (2%, p = 0.031). One-year success rates were significantly higher in the 25G group compared to the 27G group for both QS18 (25G: 67.9% vs. 27G: 35.7%, p = 0.002) and FS18 (25G: 63.6% vs. 27G: 29.2%, p = 0.007). Conclusions: The PreserFlo microshunt is an effective and safe glaucoma surgery with a low rate of bleb revisions or needlings. We show that the 25G needle tract might be more efficient for IOP control at the cost of increased IOP-related complications compared to 27G.

Thermally tuned VCSEL at 850†nm as a low-cost alternative source for full-eye SS-OCT.

Swept-source optical coherence tomography (SS-OCT) demonstrates superior performance in comparison to spectral domain OCT with regard to depth ranging. The main driver of cost for SS-OCT systems is, however, the price of the source. Here we show a low-cost alternative swept source that uses a thermally tuned vertical-cavity surface-emitting laser (VCSEL) at 850 nm. Its center wavelength can be tuned by adjusting the operating temperature through modulation of the injection current. At 2 kHz sweep rate, the depth range of the system was 5 cm, with a sensitivity roll-off of under -3 dB across this range. The system achieved a sensitivity of 97 dB with a sample beam power of 0.3 mW and an axial resolution of 50 µm in air. To demonstrate the system performance in vivo, an eye of a healthy volunteer was measured, and full-eye scans were acquired at 25 and 50 kHz from the cornea to the retina. Based on our results, we believe that this technology can be used as a cost-effective alternative OCT for point-of-care diagnostics.

Characteristics of Henle's fiber layer in healthy and glaucoma eyes assessed by polarization-sensitive optical coherence tomography.

Using conventional optical coherence tomography (OCT), it is difficult to image Henle fibers (HF) due to their low backscattering potential. However, fibrous structures exhibit form birefringence, which can be exploited to visualize the presence of HF by polarization-sensitive (PS) OCT. We found a slight asymmetry in the retardation pattern of HF in the fovea region that can be associated with the asymmetric decrease of cone density with eccentricity from the fovea. We introduce a new measure based on a PS-OCT assessment of optic axis orientation to estimate the presence of HF at various eccentricities from the fovea in a large cohort of 150 healthy subjects. By comparing a healthy age-matched sub-group (N = 87) to a cohort of 64 early-stage glaucoma patients, we found no significant difference in HF extension but a slightly decreased retardation at about 2° to 7.5° eccentricity from the fovea in the glaucoma patients. This potentially indicates that glaucoma affects this neuronal tissue at an early state.

Quantitative assessment of depolarization by the retinal pigment epithelium in healthy and glaucoma subjects measured over a large field of view.

We present measurements of depolarization introduced by the retinal pigment epithelium (RPE) over a 45° field of view using polarization sensitive optical coherence tomography. A detailed spatial distribution analysis of depolarization caused by the RPE is presented in a total of 153 subjects including both healthy and diseased eyes. Age and sex related differences in the depolarizing character of the RPE are investigated.

Birefringent Properties of the Peripapillary Retinal Nerve Fiber Layer in Healthy and Glaucoma Subjects Analyzed by Polarization-Sensitive OCT.

Purpose: To study the circumpapillary retinal nerve fiber layer (RNFL) birefringence (BIR) of early glaucoma and age-matched healthy eyes using polarization-sensitive optical coherence tomography (PS-OCT). Methods: In this prospective cross-sectional study, we compared virtual circular PS-OCT B-scans with a diameter of 3.5 mm centered on the optic disc (OD) acquired with a PS-OCT prototype (860 nm center wavelength). Early glaucoma was defined by the glaucomatous appearance of the OD and a pathologic visual field test with a mean deviation (MD) better than -6 dB. The main outcome parameters were BIR, RNFL-thickness (RNFL-T), and phase retardation (RET). The BIR value at each virtual A-scan position was the quotient of the RET measured at the inner segment/outer segment junction divided by the RNFL-T. Results: The dataset comprised 49 early glaucoma patients (mean ± standard deviation [SD]: 64 ± 10 years) and 49 healthy control subjects (61 ± 9 years). Glaucomatous eyes showed a statistically significant lower BIR globally (mean ± SD: 0.108 ± 0.008°/µm vs. 0.112 ± 0.009°/µm, P = 0.033), superiorly (0.116 ± 0.017°/µm vs. 0.126 ± 0.013°/µm, P = 0.0001), and inferiorly (0.112 ± 0.011°/µm vs. 0.121 ± 0.011°/µm, P < 0.0001), and increased BIR in the temporal quadrant (0.088 ± 0.015°/µm vs. 0.078 ± 0.014°/µm, P = 0.0001) compared to healthy eyes. Conclusions: We report a reduced BIR of the RNFL in early perimetric glaucoma, which can be interpreted as a sign of loss or change of intracellular microtubules and may contribute to a better understanding of early disease development. Prospective longitudinal studies are needed to determine whether BIR is altered in pre-perimetric human glaucoma before RNFL-T decline.

Estimating the Effects of Non-Pharmaceutical Interventions and Population Mobility on Daily COVID-19 Cases: Evidence from Ontario.

This study uses coronavirus disease 2019 (COVID-19) case counts and Google mobility data for 12 of Ontario's largest Public Health Units from Spring 2020 until the end of January 2021 to evaluate the effects of non-pharmaceutical interventions (NPIs; policy restrictions on business operations and social gatherings) and population mobility on daily cases. Instrumental variables (IV) estimation is used to account for potential simultaneity bias, because both daily COVID-19 cases and NPIs are dependent on lagged case numbers. IV estimates based on differences in lag lengths to infer causal estimates imply that the implementation of stricter NPIs and indoor mask mandates are associated with reductions in COVID-19 cases. Moreover, estimates based on Google mobility data suggest that increases in workplace attendance are correlated with higher case counts. Finally, from October 2020 to January 2021, daily Ontario forecasts from Box-Jenkins time-series models are more accurate than official forecasts and forecasts from a susceptible-infected-removed epidemiology model.

Cette étude cherche à évaluer les effets des interventions non pharmaceutiques (INPs; restrictions sur les activités commerciales et rassemblements sociaux) et de la mobilité de la population sur le nombre de cas d'infection par jour, en utilisant les nombres de cas d'infection par la maladie à coronavirus 2019 (COVID-19) et les données de mobilité de Google pour 12 des plus grands Bureaux de Santé publique de l'Ontario entre le printemps 2020 et la fin janvier 2021. La méthode des variables instrumentales (VI) permet de rendre compte d'un biais potentiel de simultanéité puisque les taux quotidiens de COVID-19 et les INPs dépendent, tous les deux, du nombre de cas décalés. Les estimations par les VI basées sur les différences de durée des décalages d'ajustement pour inférer des estimations causales impliquent que de plus strictes INPs et le port obligatoire du masque dans les endroits fermés sont associés à une réduction de cas d'infection. Par ailleurs, Les estimations basées sur les données de mobilité de Google montrent que la présence accrue sur le lieu du travail est corrélée avec un plus grand nombre de cas d'infection. Finalement, d'octobre 2020 à Janvier 2021, les prévisions faites à partir de modèles de Box-Jenkins en série chronologique s'avèrent plus précises que les prévisions officielles et que celles utilisant le modèle épidémiologique susceptible ­ infecté ­ retiré.

Automatic retinal nerve fiber bundle tracing based on large field of view polarization sensitive OCT data.

A technique to accurately estimate trajectories of retinal nerve fiber bundles (RNFB) in a large field of view (FOV) image covering 45° is described. The method utilizes stitched projections of polarization-sensitive optical coherence tomography (PS-OCT) data, as well as a mathematical model of average RNFB trajectories as prior. The fully automatic process was applied to data recorded in healthy subjects and glaucoma patients and automatically detected individual RNFB trajectories are compared to manual traces.

Temporal phase evolution OCT for measurement of tissue deformation in the human retina in-vivo.

We demonstrate the use of temporal phase evolution (TPE-) OCT methods to evaluate retinal tissue deformation in-vivo over time periods of several seconds. A custom built spectral domain (SD)-OCT system with an integrated retinal tracker, ensuring stable imaging with sub-speckle precision, was used for imaging. TPE-OCT measures and images phase differences between an initial reference B-scan and each of the subsequent B-scans of the evaluated temporal sequence. In order to demonstrate the precision and repeatability of the measurements, retinal nerve fiber (RNF) tissue deformations induced by retinal vessels pulsating with the heartbeat were analyzed in several healthy subjects. We show TPE maps (M-scans of phase evolution as a function of position along B-scan trace vs. time) of wrapped phase data and corresponding deformation maps in selected regions of the RNF layer (RNFL) over the course of several cardiac cycles. A reproducible phase pattern is seen at each heartbeat cycle for all imaged volunteers. RNF tissue deformations near arteries and veins up to ∼ 1.6 µm were obtained with an average precision for a single pixel of about 30 nm. Differences of motion induced by arteries and veins are also investigated.

Needling and open filtering bleb revision after XEN-45 implantation-a retrospective outcome comparison.

PURPOSE: To compare efficacy and safety of needling and open bleb revision after XEN-45 surgery. METHODS: This retrospective study represents real-life data of patients who underwent XEN-45 surgery between November 2014 and June 2018 in the Vienna General Hospital. The following groups were formed for data evaluation: (PSEA) primary surgery secondary intervention allowed (n = 268); (PS) primary surgery until secondary intervention (n = 268); (N) first needling until additional secondary intervention (n = 55); (BR) first bleb revision until additional secondary intervention (n = 105). Main outcome measures were pre- and postoperative intraocular pressure (IOP), number of glaucoma medication (GM), Kaplan-Meier success rates, and secondary intervention rates. Success was defined as postoperative IOP < 21 mmHg and < 18 mmHg together with ≥ 20% IOP reduction with medication allowed. RESULTS: IOP (and GM) was lowered from 23.5 ± 8.0 (GM 3.1 ± 1.0) to 14.9 ± 8.2 mmHg (1.2 ± 1.4) in group PSEA and 18.1 ± 8.2 mmHg (1.5 ± 1.4) in group PS, in group N from 23.2 ± 10.1 (1.5 ± 1.0) to 19.3 ± 8.5 mmHg (2.2 ± 1.3) and in group BR from 22.0 ± 8.0 mmHg (2.5 ± 1.1) to 15.5 ± 6.4 mmHg (1.3 ± 1.5) after a median follow-up of 16.0, 8.4, 4.8, and 7.3 months, respectively. Success rates at 1 year were significantly higher in group BR (50.7%) compared to PS (37.7%, p = 0.019) and N (24.3%; p = 0.015). An additional intervention was required less frequently in group BR (17.1%) compared to group PS (49.6%, p < 0.001) and group N (54.5%, p < 0.001). CONCLUSION: Our data appear to indicate favorable outcomes for open XEN bleb revision in terms of Kaplan-Meier success rates and secondary intervention rate compared to the needling procedure.

Early Identification of Retinal Neuropathy in Subclinical Diabetic Eyes by Reduced Birefringence of the Peripapillary Retinal Nerve Fiber Layer.

Purpose: To study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT). Methods: In this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC). Results: Out of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group. Conclusions: We identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

An overview and critique of the use of cumulative sum methods with surgical learning curve data.

Cumulative sum (CUSUM) plots and methods have wide-ranging applications in healthcare. We review and discuss some issues related to the analysis of surgical learning curve (LC) data with a focus on three types of CUSUM statistical approaches. The underlying assumptions, benefits, and weaknesses of each approach are given. Our primary conclusion is that two types of CUSUM methods are useful in providing visual aids, but are subject to overinterpretation due to the lack of well-defined decision rules and performance metrics. The third type is based on plotting the CUSUM of the differences between observations and their average value. We show that this commonly applied retrospective method is frequently interpreted incorrectly and is thus unhelpful in the LC application. Curve-fitting methods are more suitable for meeting many of the goals associated with the study of surgical LCs.

Analysis of retinal nerve fiber layer birefringence in patients with glaucoma and diabetic retinopathy by polarization sensitive OCT.

The retinal nerve fiber layer (RNFL) is a fibrous tissue that shows form birefringence. This optical tissue property is related to the microstructure of the nerve fiber axons that carry electrical signals from the retina to the brain. Ocular diseases that are known to cause neurologic changes, like glaucoma or diabetic retinopathy (DR), might alter the birefringence of the RNFL, which could be used for diagnostic purposes. In this pilot study, we used a state-of-the-art polarization sensitive optical coherence tomography (PS-OCT) system with an integrated retinal tracker to analyze the RNFL birefringence in patients with glaucoma, DR, and in age-matched healthy controls. We recorded 3D PS-OCT raster scans of the optic nerve head area and high-quality averaged circumpapillary PS-OCT scans, from which RNFL thickness, retardation and birefringence were derived. The precision of birefringence measurements was 0.005°/µm. As compared to healthy controls, glaucoma patients showed a slightly reduced birefringence (0.129 vs. 0.135°/µm), although not statistically significant. The DR patients, however, showed a stronger reduction of RNFL birefringence (0.103 vs. 0.135°/µm) which was highly significant. This result might open new avenues into early diagnosis of DR and related neurologic changes.

Swiss Startup Framework: A Highly Effective Network Supporting the Generation of Emerging Biotech Businesses.

For over 50 years, Switzerland has been one of the leading countries driving innovation in biotechnology and its industrial applications. Today, some 1,000 biotech companies form a tightly knit, cross-functional network ranging from research through to manufacturing. This network comprises R&D companies, contract research organizations, and highly specialized advisors and biotech investors. Together, they form an external innovation pool that complements the in-house R&D capacity of the large multi-national pharma companies. A highly effective startup framework, solid acceleration mechanisms, and innovative investors enable the emergence of a continuous flow of biotech startups that revitalize the industry with new technologies and products supporting drug development and diagnostics.

Generating large field of view en-face projection images from intra-acquisition motion compensated volumetric optical coherence tomography data.

A technique to generate large field of view projection maps of arbitrary optical coherence tomography (OCT) data is described. The technique is divided into two stages - an image acquisition stage that features a simple to use fast and robust retinal tracker to get motion free retinal OCT volume scans - and a stitching stage where OCT data from different retinal locations is first registered against a reference image using a custom pyramid-based approach and finally stitched together into one seamless large field of view (FOV) image. The method is applied to data recorded with a polarization sensitive OCT instrument in healthy subjects and glaucoma patients. The tracking and stitching accuracies are quantified, and finally, large FOV images of retinal nerve fiber layer retardation that contain the arcuate nerve fiber bundles from the optic nerve head to the raphe are demonstrated.

Using telematics data to find risky driver behaviour.

Usage-based insurance schemes provide new opportunities for insurers to accurately price and manage risk. These schemes have the potential to better identify risky drivers which not only allows insurance companies to better price their products but it allows drivers to modify their behaviour to make roads safer and driving more efficient. However, for Usage-based insurance products, we need to better understand how driver behaviours influence the risk of a crash or an insurance claim. In this article, we present our analysis of automotive telematics data from over 28 million trips. We use a case control methodology to study the relationship between crash drivers and crash-free drivers and introduce an innovative method for determining control (crash-free) drivers. We fit a logistic regression model to our data and found that speeding was the most important driver behaviour linking driver behaviour to crash risk.

The k conditional nearest neighbor algorithm for classification and class probability estimation.

The k nearest neighbor (kNN) approach is a simple and effective nonparametric algorithm for classification. One of the drawbacks of kNN is that the method can only give coarse estimates of class probabilities, particularly for low values of k. To avoid this drawback, we propose a new nonparametric classification method based on nearest neighbors conditional on each class: the proposed approach calculates the distance between a new instance and the kth nearest neighbor from each class, estimates posterior probabilities of class memberships using the distances, and assigns the instance to the class with the largest posterior. We prove that the proposed approach converges to the Bayes classifier as the size of the training data increases. Further, we extend the proposed approach to an ensemble method. Experiments on benchmark data sets show that both the proposed approach and the ensemble version of the proposed approach on average outperform kNN, weighted kNN, probabilistic kNN and two similar algorithms (LMkNN and MLM-kHNN) in terms of the error rate. A simulation shows that kCNN may be useful for estimating posterior probabilities when the class distributions overlap.

Nearest labelset using double distances for multi-label classification.

Multi-label classification is a type of supervised learning where an instance may belong to multiple labels simultaneously. Predicting each label independently has been criticized for not exploiting any correlation between labels. In this article we propose a novel approach, Nearest Labelset using Double Distances (NLDD), that predicts the labelset observed in the training data that minimizes a weighted sum of the distances in both the feature space and the label space to the new instance. The weights specify the relative tradeoff between the two distances. The weights are estimated from a binomial regression of the number of misclassified labels as a function of the two distances. Model parameters are estimated by maximum likelihood. NLDD only considers labelsets observed in the training data, thus implicitly taking into account label dependencies. Experiments on benchmark multi-label data sets show that the proposed method on average outperforms other well-known approaches in terms of 0/1 loss, and multi-label accuracy and ranks second on the F-measure (after a method called ECC) and on Hamming loss (after a method called RF-PCT).

Comparing and Monitoring Risk-Adjusted Hospital Performance Measures: A Weighted Estimating Equations Approach.

Background. There is a great deal of interest in evaluating hospital performance in order to monitor and improve health care quality. Increasingly, risk-adjusted performance measures are available to the public and statistical approaches for estimating these measures are considered. Some methods in use currently are based on 3-year aggregates of data since a small number of cases may lead to imprecise estimates and make it hard for stakeholders to detect differences across hospitals over time. However, if quality changes over time, a measure based on these data is a biased estimate of present performance. Methods. We present an alternative approach (weighted estimating equations [WEE]) for combining historical data in estimation that regulates the tradeoff between bias and precision in the measure of present performance. The WEE approach uses all available historical data through estimating functions that down-weight past data. Results. We compare the WEE approach to two current practices using a realistic dataset of the mortality of patients following an elective percutaneous coronary intervention procedure in New York State who meet certain criteria. The width of the uncertainty interval in the realistic example is up to 65% smaller and the difference is more pronounced for hospitals with a small number of cases. Conclusions. The advantage of this approach extends from the example dataset to other datasets. The WEE approach uses all available data rather than data from an arbitrary 3-year window. The effect of borrowing strength from historical data is a more precise estimate of present performance than current practices. Its advantages are important for the comparison of other aspects of medical performance, including surgical or medical practitioner performance.

Comparing heteroscedastic measurement systems with the probability of agreement.

Deciding whether two measurement systems agree well enough to be used interchangeably is important in medical and clinical contexts. Recently, the probability of agreement was proposed as an alternative to comparison techniques such as correlation, regression, and the limits of agreement approach, when the systems' measurement errors are homoscedastic. However, in medical and clinical contexts, it is common for measurement variability to increase proportionally with the magnitude of measurement. In this article, we extend the probability of agreement analysis to accommodate heteroscedastic measurement errors, demonstrating the versatility of this simple metric. We illustrate its use with two examples: one involving the comparison of blood pressure measurement devices, and the other involving the comparison of serum cholesterol assays.