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To develop deep learning models for annualized geographic atrophy (GA) growth rate prediction using fundus autofluorescence (FAF) images and spectral-domain OCT volumes from baseline visits, which can be used for prognostic covariate adjustment to increase power of clinical trials.This retrospective analysis estimated GA growth rate as the slope of a linear fit on all available measurements of lesion area over a 2-year period. Three multitask deep learning models-FAF-only, OCT-only, and multimodal (FAF and OCT)-were developed to predict concurrent GA area and annualized growth rate.Patients were from prospective and observational lampalizumab clinical trials.The 3 models were trained on the development data set, tested on the holdout set, and further evaluated on the independent test sets. Baseline FAF images and OCT volumes from study eyes of patients with bilateral GA (NCT02247479; NCT02247531; and NCT02479386) were split into development (1279 patients/eyes) and holdout (443 patients/eyes) sets. Baseline FAF images from study eyes of NCT01229215 (106 patients/eyes) and NCT02399072 (169 patients/eyes) were used as independent test sets.Model performance was evaluated using squared Pearson correlation coefficient (rOn the holdout data set, rWe show the feasibility of using baseline FAF images and OCT volumes to predict individual GA area and growth rates using a multitask deep learning approach. The deep learning-based growth rate predictions could be used for covariate adjustment to increase power of clinical trials.

GDC‐0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC‐0334 were evaluated in this first‐in‐human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC‐0334 in guinea pigs, rats, dogs, and monkeys. Human PK and PK‐PD of GDC‐0334 were characterized after single and multiple oral dosing using a population modeling approach. The ability of GDC‐0334 to inhibit dermal blood flow (DBF) induced by topical administration of allyl isothiocyanate (AITC) was evaluated as a target‐engagement biomarker. Quantitative models were developed iteratively to refine the parameter estimates of the dose‐concentration‐effect relationships through stepwise estimation and extrapolation. Human PK analyses revealed that bioavailability, absorption rate constant, and lag time increase when GDC‐0334 was administered with food. The inhibitory effect of GDC‐0334 on the AITC‐induced DBF biomarker exhibited a clear sigmoid‐Emax relationship with GDC‐0334 plasma concentrations in humans. This study leveraged emerging preclinical and clinical data to enable iterative refinement of GDC‐0334 mathematical models throughout the FIH study for dose selection in subsequent cohorts throughout the study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? GDC‐0334 is a novel, small molecule TRPA1 inhibitor and a pharmacokinetic‐pharmacodynamic (PK‐PD) modeling strategy could be implemented in a systematic and step‐wise manner to build and learn from emerging data for early clinical development. WHAT QUESTION DID THIS STUDY ADDRESS? Can noncompartmental and population‐based analyses be used to describe the PK and PD characteristics of GDC‐0334 in preclinical and clinical studies? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? GDC‐0334 exposure generally increased with dose in rats, dogs, and monkeys. The starting dose (25 mg) in the clinical study was determined based on the preclinical data. GDC‐0334 exhibited linear PK in humans and the bioavailability was increased with food. The inhibitory effect of GDC‐0334 on dermal blood flow induced by the TRPA1 agonist allyl isothiocyanate in humans indicates a clear PK‐PD relationship. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The models developed based on TRPA1 agonist‐induced dermal blood flow inhibition data can be used to predict PK‐PD relationships in future preclinical and clinical studies evaluating new drug entities that target TRPA1.

BackgroundThe basis of Age-related macular degeneration (AMD) genetic risk has been well documented; however, few studies have looked at genetic biomarkers of disease progression or treatment response within advanced AMD patients. Here we report the first genome-wide analysis of genetic determinants of low-luminance vision deficit (LLD), which is seen as predictive of visual acuity loss and anti-VEGF treatment response in neovascular AMD patients.MethodsAMD patients were separated into small- and large-LLD groups for comparison and whole genome sequencing was performed. Genetic determinants of LLD were assessed by common and rare variant genetic analysis. Follow-up functional analysis of rare coding variants identified by the burden test was then performed in vitro.ResultsWe identified four coding variants in the CIDEC gene. These rare variants were only present in patients with a small LLD, which has been previously shown to indicate better prognosis and better treatment response. Our in vitro functional characterization of these CIDEC alleles revealed that all decrease the binding affinity between CIDEC and the lipid droplet fusion effectors PLIN1, RAB8A and AS160. The rare CIDEC alleles all cause a hypomorphic defect in lipid droplet fusion and enlargement, resulting in a decreased fat storage capability in adipocytes.ConclusionsAs we did not detect CIDEC expression in the ocular tissue affected by AMD, our results suggest that the CIDEC variants do not play a direct role in the eye and influence low-luminance vision deficit via an indirect and systemic effect related to fat storage capacity.FundingNo external funding was received for this work.

Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT). Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained. Features preceding progression/conversion to advanced AMD (drusen, reticular pseudodrusen [RPD], MNV, incomplete/complete retinal pigment epithelium and outer retinal atrophy [iRORA/cRORA]) were assessed. Results: Of 30 fellow eyes with available follow-up images, 12 converted to GA (FAF), 2 converted to MNV, and 16 were nonconverters during the review period (median: 17.8 months). iRORA/cRORA features (present in all converters at baseline) were identified on OCT in eyes that progressed to GA. Median time interval from iRORA to cRORA and from cRORA to GA was 7 months each. GA development/progression was either drusen- or RPD-associated (n = 6 each). Eyes with baseline RPD showed faster GA progression versus eyes with drusen (1.49 vs. 0.38 mm2/year). Conclusions: RPD presence was associated with rapid GA lesion enlargement and may provide an early indication of faster GA progression.

Background and purpose Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. Experimental approach Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1-knock out (Trpa1 KO) rats, and changes in dermal blood flow (DBF) were measured by laser speckle contrast imaging. In humans, the DBF, pain and itch responses to 5-20% AITC applied to the forearm were measured and safety was evaluated. Reproducibility of the DBF, pain and itch responses to topically applied 10% and 15% AITC were assessed at two visits separated by 13-15 days. DBF changes were summarized at 5-minute intervals as areas under the curve (AUC) and maxima. Intraclass correlation coefficient (ICC) was calculated to assess arm-arm and period-period reproducibility. Key results AITC- and citric acid-induced DBF were significantly reduced in Trpa1 KO rats compared to wildtype (90 ± 2% and 65 ± 11% reduction, respectively), whereas capsaicin response did not differ. In humans, each AITC concentration significantly increased DBF compared to vehicle with the maximal increase occurring 5 minutes post application. Ten percent and 15% AITC were selected as safe and effective stimuli. AUC from 0 to 5 minutes was the most reproducible metric of AITC-induced DBF across arms (ICC = 0.92) and periods (ICC = 0.85). Subject-reported pain was more reproducible than itch across visits (ICC = 0.76 vs 0.17, respectively). Conclusion and implications AITC-induced DBF is a suitable target engagement biomarker of TRPA1 activity for preclinical and clinical studies of TRPA1 antagonists.

Purpose This study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD). Design Prospective cross-sectional study. Methods This study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomes included the area of loss, and the CCVD of degeneration in different areas was quantified and correlated. Results The total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r = 0.96; P Conclusions Photoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.

This study investigates the determinants of initial public offering (IPO) underpricing by focusing on variables relating to information asymmetry, investor sentiment and corporate governance and examines whether the determinants of IPO underpricing in high-technology and non-high-technology IPOs differ. With data from Taiwan for 2009–2011, this study finds that overallotment is negatively related to underpricing, whereas market momentum, first-day trading volume and managers’ ownership retention rates are positively related to underpricing, particularly for high-technology IPOs. Our results support the signalling hypothesis in high-technology IPOs. JEL Classification: G12, G14, G24, G32

This study set out to evaluate the financing efficiency of low‐carbon companies. Applying a three‐stage data envelopment analysis with the data from 85 listed companies in China's low‐carbon industries over the period 2011 to 2017, this study has found that the overall financing efficiency of low‐carbon companies was relatively high, and the pure technical efficiency was quite steady over the period. The overall financing efficiency of these low‐carbon companies on average tended to change with the scale efficiency. This study has also shown that the scale efficiency was the main constraint influencing the financing efficiency of low‐carbon companies in China over the period. Our results are robust and have significant implications for policy makers and corporate managers.

Geographic atrophy (GA) is late-stage dry age-related macular degeneration (AMD). Improved predictors of GA progression would be useful in clinical trial design and may be relevant for clinical practice. The purpose of this study was to accurately predict GA progression over time from baseline fundus autofluorescence (FAF) images (Heidelberg Engineering, Inc., Germany) using deep learning. Study eyes of patients (n = 1312) enrolled in the Lampalizumab trials1, 2 (NCT02479386, NCT02247479, NCT02247531) were included. The dataset was split by patient into training (n = 1047) and holdout sets (n = 265). GA progression, defined as GA lesion growth rate, was derived by a linear fit on all available measurements of GA lesion area (mm2 , measured from manually graded FAF images). The model performance was evaluated using 5-fold cross-validation (CV). Coefficient of determination (R2 ) computed as the square of Pearson correlation coefficient was used as the performance metric. Multiple modeling approaches were implemented, and the best performance was observed using cascade learning. In this approach, pre-trained weights on ImageNet were finetuned to predict GA lesion area followed by further fine-tuning to predict GA growth rate. The 5-folds had an average CV R2 of 0.44, and the holdout showed R2 of 0.50 (95% confidence interval: 0.41 - 0.61). In comparison, a linear model using only baseline GA lesion area in the same holdout showed an R2 of 0.18. Further investigation with visualization techniques might help understand the pathophysiology behind the predictions. The predictions may be improved by combining with imaging modalities like near-infrared and/or optical coherence tomography.

Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described. GDC-0334 inhibited TRPA1 function on airway smooth muscle and sensory neurons, decreasing edema, dermal blood flow (DBF), cough, and allergic airway inflammation in several preclinical species. In a healthy volunteer Phase 1 study, treatment with GDC-0334 reduced TRPA1 agonist-induced DBF, pain, and itch, demonstrating GDC-0334 target engagement in humans. These data provide therapeutic rationale for evaluating TRPA1 inhibition as a clinical therapy for asthma.

This study investigates the role of gender diversity in fraud commission and detection with a view to identifying whether companies with more female corporate leaders are less likely to be involved in financial statement fraud. Using a bivariate probit model, the role of female corporate leaders in financial statement fraud commission and detection is examined for Chinese listed companies from 2007 to 2018. The representation of female corporate leaders increases the likelihood of fraud detection, thus reducing firms’ propensity to engage in fraud. The finding confirms that women are risk averse and more committed to ethical practices than men in corporate leadership positions. Moreover, this impact of gender diversity is contingent upon the nature of ultimate controllers of listed companies: more female representation in top leadership roles can mitigate fraud commission or detect fraud effectively in non-state-owned enterprises, but not in state-owned enterprises. In addition, the recent anti-corruption campaign initiated by Chinese President Jinping Xi is a powerful form of public governance . Female corporate leaders play a more positive role in mitigating fraud commission and detecting fraud commission in the post-campaign period than in the pre-campaign period.

Purpose To use OCT angiography (OCTA)-derived quantitative metrics to assess the response of choroidal neovascularization (CNV) to pro re nata (PRN) anti–vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD). Design Prospective, longitudinal cohort study. Participants Fourteen eyes from 14 study participants with treatment-naive neovascular AMD were enrolled. Methods Participants were evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN protocol for 1 year. At each visit, two 3 × 3-mm2 OCTA scans were obtained. Custom image processing was applied to segment the outer retinal slab, suppress projection artifact, and automatically detect CNV. Choroidal neovascularization membrane area and CNV vessel area were calculated. Main Outcome Measures Individual and mean CNV membrane area and CNV vessel area at each visit; within-visit repeatability determined by coefficient of variation. Results Eight eyes showed the entire CNV to be within the 3 × 3-mm2 scanning area and had adequate image quality for CNV quantification. One patient (patient 2) was excluded from analysis because of the presence of a large subretinal hemorrhage overlying the CNV membrane. In the remaining patients, CNV vessel area was reduced by 39%, 50%, 43%, and 41% at months 1, 3, 6, and 12, respectively. Choroidal neovascularization membrane area was reduced by 39%, 51%, 54%, and 45% at months 1, 3, 6, and 12. At month 6, mean change from baseline was not statistically significant for CNV vessel area, whereas it was statistically significant for CNV membrane area. Neither metric was significantly different compared with baseline at month 12. Individual analyses revealed each CNV had a unique response under PRN treatment. Within-visit repeatability was 7.96% (coefficient of variation) for CNV vessel area and 7.37% for CNV membrane area. Conclusions In this small exploratory study of CNV response to PRN anti-VEGF treatment, both CNV vessel area and membrane area were reduced compared with baseline after 3 months. After 1 year of follow-up, these reductions were no longer statistically significant. When anti-VEGF treatment was withheld, increasing CNV vessel area over time often resulted in exudation, but it was not possible to determine exactly when exudation occurs.

This study investigates the impact of economic freedom (EcF) on analysts’ earnings forecast (AEF) accuracy. EcF is measured from five aspects: Government, Protection, Money, Trade, and Regulation. With the sample of 7,014 firms from 12 economies in the Asia-Pacific region over the 18-year period, this study finds an optimistic bias in AEFs. The optimistic bias is stronger for large firms, value firms, stock with high analyst coverage, and low dispersion in AEFs. Also, the optimistic bias is stronger from analysts in economies with less EcF than in more freedom ones. Analysts are making more accurate earnings forecasts for firms in economies with more EcF. In addition, the study finds the optimism bias reduced the earnings forecast accuracy. These findings may suggest that an increase of EcF would lead to more transparent financial statements, which further reduces the analysts’ forecast bias.

Purpose To determine the sensitivity and specificity of OCT angiography (OCTA) in the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Design Prospective case series. Subjects A prospective series of 72 eyes were studied, which included eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal controls. Methods All eyes underwent OCTA with a spectral domain OCT. The 3-dimensional angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram, and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence of CNV. Main Outcome Measure The sensitivity and specificity of CNV detection compared to the gold standard of fluorescein angiography and OCT was determined for structural spectral domain OCT alone, en face OCTA alone, and with en face OCTA combined with cross-sectional OCTA. Results Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage and sensitivity improved to 94% for both graders if eyes with subretinal hemorrhage were excluded. The addition of cross-sectional OCTA along with en face OCTA improved the sensitivity to 100% for both graders. Structural OCT alone also had a sensitivity of 100%. The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader B. The specificity of structural OCT alone was 97.5% for grader A and 85% for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5% for grader A and 100% for grader B. Conclusions Sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approaches that of the gold standard of fluorescein angiography with OCT, and it is better than en face OCTA alone. Structural OCT alone has excellent sensitivity for CNV detection. False positives from structural OCT can be mitigated with the addition of flow information with OCTA.

Purpose To develop deep learning (DL) models to predict best-corrected visual acuity (BCVA) from optical coherence tomography (OCT) images from patients with neovascular age-related macular degeneration (nAMD). Methods Retrospective analysis of OCT images and associated BCVA measurements from the phase 3 HARBOR trial (NCT00891735). DL regression models were developed to predict BCVA at the concurrent visit and 12 months from baseline using OCT images. Binary classification models were developed to predict BCVA of Snellen equivalent of

Die AngioVue-Technologie von Optovue für die optische Kohärenztomographie-Angiographie (OCT-A) basiert auf dem Bildgebungssystem AngioVue (Optovue Inc., Freemont, CA, USA) unter Verwendung des SSADA(split-spectrum amplitude-decorrelation angiography)-Algorithmus. Dieser Algorithmus ist darauf ausgelegt, die Dauer des Scan-Vorgangs zu minimieren. Er erkennt Bewegung im Blutgefäßlumen durch die Messung der Veränderungen in der reflektierten OCT-Signalamplitude bei aufeinanderfolgenden Querschnitt-Scans. Die Besonderheit der SSADA liegt in der Art, wie das OCT-Signal weiterverarbeitet wird, um die Flussmessung zu verbessern und das Signalrauschen der axialen Grundbewegung zu eliminieren. Konkret trennt der Algorithmus die OCT-Aufnahme in einzelne Spektralbänder auf und steigert dadurch die Anzahl verwertbarer Bild-Frames. Jeder neue Frame hat eine geringere axiale Auflösung, die weniger empfindlich gegenüber axialen Augenbewegungen infolge des pulsierenden Blutstroms ist. Die Technologie des AngioVue-Systems von Optovue ermöglicht eine quantitative Analyse. Sie liefert nummerische Daten über durchströmte sowie nicht durchströmte Areale und kann Flussdichtekarten erstellen. Diese aufbereiteten Messdaten könnten als Biomarker sowohl für die Diagnose als auch für die Überwachung des Krankheitsverlaufs und des Ansprechens auf eine Therapie dienen. Durchströmte Areale: Die Software berechnet das eingezeichnete Areal und das Gefäßareal in mm2. Sie ermöglicht auch den Vergleich aller Messungen einer Person. Nicht durchströmte Areale: Die Software zeigt die nicht durchbluteten Areale per Mausklick an. Ischämische Areale werden in Gelb dargestellt. Diese Areale können abgespeichert und mit anderen in der Studie abgeglichen werden. Mit dem Flussdichte-Tool lässt sich der prozentuale Anteil von vaskulären Arealen in En-Face-Angiogrammen messen. Die Analyse beruht auf einem ETDRS(Early Treatment Diabetic Retinopathy Study)-Raster, das wie die Dickenkarte auf die Makula zentriert ist. Das Tool ist sowohl für den inneren als auch für den äußeren Gefäßplexus geeignet. Übersetzung aus Dev Ophthalmol. Basel, Karger, 2016, vol 56, pp 6-12 (DOI:10.1159/000442770)

Purpose To evaluate the morphological structure of ill-defined choroidal neovascularisation (CNV) with traditional fluorescein angiography (FA) compared with optical coherence tomographic angiography (OCTA). Methods A retrospective case series study of 11 eyes with ill-defined CNV on FA was performed. Eyes were scanned with commercially available spectral-domain optical coherence tomography (OCT) (70 000 A-scans/s). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. En face OCT angiograms were compared with FA. Results Eleven cases of ill-defined CNV on FA were identified from 10 study participants. Mean age of the participants was 74.5±6.8 years. Six cases had late leakage from undetermined source (LLUS) and five had fibrovascular pigment epithelial detachment (FVPED). Combining cross-sectional structural OCT with OCT angiograms, all cases were found to have type 1 CNV that corresponded to occult CNV with FA. In all cases of occult CNV on FA, distinct vascular structures were visible with OCTA in the outer retinal/retinal pigment epithelium slab. The mean CNV vessel area was 2.61±3.65 mm 2 . The mean CNV vessel area in cases with FVPED was larger than that in cases with LLUS (4.69±4.72 mm 2 compared with 0.85±0.90 mm 2 , Mann-Whitney p value=0.04). Conclusions Although the sample size is small to draw conclusions and the nature of work is retrospective and descriptive, OCTA has the potential to improve visualisation of ill-defined CNV with dye-based angiography, including occult CNV.

PurposeThe purpose of this paper is to explore whether any discrepancy exists between the disclosed in SSB reports of Islamic banks and the disclosure index which was based on stakeholders’ expectation.Design/methodology/approachThis study uses contents analysis as the research method to explore Shariâ’ah audit reporting practices of Islamic Banks.FindingsThe study finds that the level of disclosures overall by IFIs in the sample is rather low compared to the stakeholder expectations.Practical implicationsThis paper has important implication for policy makers as it contribute to the debate on that uniform disclosure standards across the globe need to be implemented to ensure a uniform level of disclosure by Islamic banks.Originality/valueThis study is amongst the few studies that examine and explore the nature and extent ofShari’ahSupervisory Board in Islamic banks.

Purpose To elucidate the relationship between vessel density (VD) measurements and signal strength in OCT angiography (OCTA). Design Cross-sectional study. Participants Healthy volunteers. Methods OCT angiography images obtained from healthy volunteers were analyzed to demonstrate the relationship between signal strength index (SSI) and VD. Experiments were performed to determine the effects of signal strength reduction on VD measurements on the Optovue/AngioVue (Optovue, Inc, Fremont, CA) and Cirrus/AngioPlex OCTA (Carl Zeiss Meditec, Inc, Dublin, CA) systems. Signal strength reduction was generated by either neutral density filters (NDFs) or defocus. Main Outcome Measures Regression analysis of signal strength effects on VD. Results Vessel density decreased linearly with signal strength with high statistical significance on both OCTA systems tested and for all analyzed sources of variation in signal strength. The slope of VD versus SSI was greatest when signal strength was adjusted by NDFs, followed by defocus, interscan difference, interindividual variation, and left–right eye difference. Multivariate analysis revealed that both SSI and age had a significant effect on the interindividual variation in VD. Conclusions Vessel density measurements using OCTA were affected significantly by OCT signal strengths on 2 OCTA platforms. Investigators should exercise caution when interpreting VD data from OCTA scans. Quantification algorithms for OCTA should ideally remove the signal strength bias.

OBJECTIVE: To evaluate the projection-resolved (PR) optical coherence tomography angiography (OCTA) algorithm in detecting plexus-specific vascular abnormalities in retinal pathologies. DESIGN: Cross-sectional observational clinical study PARTICIPANTS: Patients diagnosed with retinal vascular diseases and healthy volunteers. METHODS: Eyes were imaged using an OCT system operating at 840 nm and employing the split-spectrum amplitude decorrelation algorithm. A novel algorithm suppressed projection artifacts inherent to OCTA. The volumetric scans were segmented and visualized on different plexuses. MAIN OUTCOME MEASURES: Qualitative observation of vascular abnormalities on both cross-sectional and en face PR-OCTA images. RESULTS: Eight illustrative cases are reported. In cases of diabetic retinopathy, retinal vessel occlusion, and retinitis pigmentosa, PR-OCTA detected retinal nonperfusion regions within deeper retinal plexuses not visualized by conventional OCTA. In age-related macular degeneration, cross-sectional PR-OCTA permitted the classification of choroidal neovascularization, and, in a case of retinal angiomatous proliferation, identified a vertical vessel contiguous with the deep capillary plexus. In macular telangiectasia, PR-OCTA detected a diving perifoveal vein and delineated subretinal neovascularization. CONCLUSIONS: Application of PR-OCTA promises to improve sensitive, accurate evaluation of individual vascular plexuses in multiple retinal diseases.

This study investigated the current perceptions and practices of financial risk management at small businesses in China. The researchers took an interpretative approach, using interviews within a case study, to collect qualitative data from Chinese business owners. Despite the well-documented importance of financial risk management in light of the 2008 global financial crises, surprisingly, the data indicated that little progress has been made on implementing an effective financial risk management in many Chinese small businesses. Analysis indicated the core problems in the case study organization stemmed from a lack of expertise, along with insufficient operational resources, for applying risk management. Interestingly, the researchers also found that Chinese small business managers perceived financial risks differently from managers of large organizations in China. Specifically, small business owners preferred to utilize risk transfer and insurance cover to hedge against financial risk.

The use of stock options and credit default swaps (CDS) in banks is not uncommon. Stock options can induce risk-taking incentives, while CDS can be used to hedge against credit risk. Building on the existing literature on executive compensation and risk management, our study contributes novel empirical support for the role of stock options in restraining the use of CDS for hedging purposes. Based on data of CEO stock options and CDS held by 60 European banks during the period 2006–2011, we find a negative relationship between option-induced risk-taking incentives (vega) and the proportion of CDS held for hedging. However, the extent of CDS held for hedging is found to be positively related to default risk in the period leading to the financial crisis that erupted in 2007. The findings imply that restraining the use of stock options can incentivize hedging with CDS, but this risk management strategy will not necessarily produce lower default risk in times of systemic credit crisis.

Diabetic retinopathy is a microangiopathy that causes capillary occlusion, vascular hyperpermeability, and neovascularization in the retinal vasculature.1 Detailed clinical examination for grading disease severity for risk of progression and vision loss is the standard of care2, but ophthalmic angiography has played a critical role in understanding and care of the disease. Early Treatment of Diabetic Retinopathy Study (ETDRS) examined the fluorescein angiographic features of the posterior pole of patients with non-proliferative diabetic retinopathy and correlated the specific features with their risk of disease progression. 3,4 Fluorescein angiography (FA) is also used to identify retinal neovascularization (RNV) in situations where clinical examination cannot detect RNV or distinguish from other anomalous appearing vessels on the retinal surface. While angiography provides valuable additional information compared to clinical examination or fundus photography, it is not part of the routine diabetic eye examination. FA requires venipuncture and intravenous injection of a dye that has a moderate risk of nausea and a rare but well documented risk of anaphylaxis and death. 5 Also, a standard protocol FA acquires images over 10 minutes with repeated exposure to a very bright light source, 6 which can cause significant discomfort for patients. Optical coherence tomography (OCT) angiography, a novel imaging technique that uses decorrelation between resampled images to detect flow to construct 2- and 3-dimensional images of blood flow within the eye, offers an alternative angiographic technique without some of the drawbacks of FA. Our group has developed the split-spectrum amplitude decorrelation algorithm (SSADA) for efficiently detecting flow signals for angiography. 7 Applying this algorithm, an OCT angiogram in areas up to 6 × 6 mm area can be acquired in 3.5 seconds without intravenous injection. This study describes features of diabetic retinopathy as seen on OCT angiography.