Effect of Intraocular Forward Scattering and Corneal Higher-Order Aberrations on Visual Acuity after Descemet’s Stripping Automated Endothelial Keratoplasty

Purpose

To assess the relationship of intraocular forward scattering and corneal higher-order aberrations (HOAs) with best spectacle corrected visual acuity (BSCVA) after Descemet’s stripping automated endothelial keratoplasty (DSAEK), and to compare these parameters between DSAEK and non-Descemet’s stripping automated endothelial keratoplasty (n-DSAEK) groups.

Methods

This retrospective study enrolled thirty eyes of 30 consecutive patients who underwent standard DSAEK, and who underwent successful phacoemulsification with intraocular lens implantation before DSAEK. The mean age at the time of surgery was 71.7 ± 10.4 years. We quantitatively evaluated the objective scattering index (OSI) using the double-pass instrument (OQAS II, Visiometrics) and corneal HOAs using Hartmann-Shack aberrometry (KR-9000PW, Topcon) 3 months postoperatively.

Results

The mean OSI, corneal HOAs, and logMAR BSCVA 3 months after DSAEK were 7.91 ± 3.58, 0.43 ± 0.27 μm, and 0.32 ± 0.25, respectively. We found a significant correlation between the OSI and logMAR BSCVA (Spearman correlation coefficient r=0.714, p<0.001), but no significant association between corneal HOAs and logMAR BSCVA 3 months postoperatively (r=0.209, p=0.267). We found no significant differences in any postoperative parameters between the DSAEK and n-DSAEK groups (p>0.05).

Conclusions

Our pilot study demonstrated that the postoperative corrected visual acuity was significantly correlated with intraocular forward scattering, but not with corneal HOAs in post-DSAEK eyes, suggesting that intraocular forward scattering plays a more essential role in postoperative visual performance than corneal aberrations after DSAEK. The detailed visual performance, such as HOAs and intraocular scattering, after n-DSAEK appears to be essentially equivalent to that after DSAEK.     

Visual acuity and associated factors. The Central India Eye and Medical Study

Visual acuity is a major parameter for quality of vision and quality of life. Information on visual acuity and its associated factors in rural societies almost untouched by any industrialization is mostly non-available. It was, therefore, the purpose of our study to determine the distribution of visual acuity and its associated factors in a rural population not marked influenced by modern lifestyle. The population-based Central India Eye and Medical Study included 4711 subjects (aged 30+ years), who underwent a detailed ophthalmologic examination including visual acuity measurement. Visual acuity measurements were available for 4706 subjects with a mean age of 49.5±13.4 years (range: 30–100 years). BCVA decreased significantly (P<0.001) from the moderately hyperopic group (0.08±0.15 logMAR) to the emmetropic group (0.16±0.52 logMAR), the moderately myopic group (0.28±0.33 logMAR), the highly hyperopic group (0.66±0.62 logMAR) and finally the highly myopic group (1.32±0.92 logMAR). In multivariate analysis, BCVA was significantly associated with the systemic parameters of lower age (P<0.001), higher level of education (P<0.001), higher body stature (P<0.001) and higher body mass index (P<0.001), and with the ophthalmic parameters of more hyperopic refractive error (spherical equivalent) (P<0.001), shorter axial length (P<0.001), lower degree of nuclear cataract (P<0.001), and lower intraocular pressure (P = 0.006). The results suggest that in the rural population of Central India, major determinants of visual acuity were socioeconomic background, body stature and body mass index, age, refractive error, cataract and intraocular pressure.     

Personalized Pseudophakic Model for Refractive Assessment

Purpose

To test a pseudophakic eye model that allows for intraocular lens power (IOL) calculation, both in normal eyes and in extreme conditions, such as post-LASIK.

Methods

Participants: The model’s efficacy was tested in 54 participants (104 eyes) who underwent LASIK and were assessed before and after surgery, thus allowing to test the same method in the same eye after only changing corneal topography.

Modelling

The Liou-Brennan eye model was used as a starting point, and biometric values were replaced by individual measurements. Detailed corneal surface data were obtained from topography (Orbscan®) and a grid of elevation values was used to define corneal surfaces in an optical ray-tracing software (Zemax®). To determine IOL power, optimization criteria based on values of the modulation transfer function (MTF) weighted according to contrast sensitivity function (CSF), were applied.

Results

Pre-operative refractive assessment calculated by our eye model correlated very strongly with SRK/T (r = 0.959, p<0.001) with no difference of average values (16.9±2.9 vs 17.1±2.9 D, p>0.05). Comparison of post-operative refractive assessment obtained using our eye model with the average of currently used formulas showed a strong correlation (r = 0.778, p<0.001), with no difference of average values (21.5±1.7 vs 21.8±1.6 D, p>0.05).

Conclusions

Results suggest that personalized pseudophakic eye models and ray-tracing allow for the use of the same methodology, regardless of previous LASIK, independent of population averages and commonly used regression correction factors, which represents a clinical advantage.     

Corneal Transplantation in Disease Affecting Only One Eye: Does It Make a Difference to Habitual Binocular Viewing?

Background

Clarity of the transplanted tissue and restoration of visual acuity are the two primary metrics for evaluating the success of corneal transplantation. Participation of the transplanted eye in habitual binocular viewing is seldom evaluated post-operatively. In unilateral corneal disease, the transplanted eye may remain functionally inactive during binocular viewing due to its suboptimal visual acuity and poor image quality, vis-à-vis the healthy fellow eye.

Methods and Findings

This study prospectively quantified the contribution of the transplanted eye towards habitual binocular viewing in 25 cases with unilateral transplants [40yrs (IQR: 32–42yrs) and 25 age-matched controls [30yrs (25–37yrs)]. Binocular functions including visual field extent, high-contrast logMAR acuity, suppression threshold and stereoacuity were assessed using standard psychophysical paradigms. Optical quality of all eyes was determined from wavefront aberrometry measurements.Binocular visual field expanded by a median 21% (IQR: 18–29%) compared to the monocular field of cases and controls (p = 0.63). Binocular logMAR acuity [0.0 (0.0–0.0)] almost always followed the fellow eye’s acuity [0.00 (0.00 –-0.02)] (r = 0.82), independent of the transplanted eye’s acuity [0.34 (0.2–0.5)] (r = 0.04). Suppression threshold and stereoacuity were poorer in cases [30.1% (13.5–44.3%); 620.8arc sec (370.3–988.2arc sec)] than in controls [79% (63.5–100%); 16.3arc sec (10.6–25.5arc sec)] (p<0.001). Higher-order wavefront aberrations of the transplanted eye [0.34μ (0.21–0.51μ)] were higher than the fellow eye [0.07μ (0.05–0.11μ)] (p<0.001) and their reduction with RGP contact lenses [0.09μ (0.08–0.12μ)] significantly improved the suppression threshold [65% (50–72%)] and stereoacuity [56.6arc sec (47.7–181.6arc sec)] (p<0.001).

Conclusions

In unilateral corneal disease, the transplanted eye does participate in gross binocular viewing but offers limited support to fine levels of binocularity. Improvement in the transplanted eye’s optics enhances its participation in binocular viewing. Current metrics of this treatment success can expand to include measures of binocularity to assess the functional benefit of the transplantation process in unilateral corneal disease.     

High Blood Pressure and Its Association with Body Weight among Children and Adolescents in the United Arab Emirates

Objectives

To estimate the prevalence of high blood pressure (BP) and its relationship with obesity among children and adolescents.

Methodology/Principal Findings

In this cross-sectional population (Emirati) representative study, we invited a random sample of 1600 students (grades 1–12) attending 23 out of all 246 schools in the Emirate of Abu Dhabi, United Arab Emirates. But analysis was restricted to Emirati nationals aged 6–17 years. We measured BP, height, weight, waist circumferences (WC), and calculated body mass index (BMI) by standard methods. BP levels ≥90^th percentile but <95^th percentile and ≥ 95^th for age, sex, and height (CDC percentiles) were classified as pre-hypertension (pre-HTN) and hypertension (HTN), respectively. Associations between BP, age, BMI, WC, and sex, were investigated by (multiple) linear regression methods. A total of 999 (47% girls) students provided complete results. The prevalence of pre-HTN was 10.5% and 11.4% and the prevalence of HTN was 15.4% and 17.8% among boys and girls, respectively. The prevalence of systolic/diastolic HTN was 14.4%/2.5% and 14.8/7.4% among boys and girls, respectively. BMI CDC percentile was positively correlated with WC percentile (r = 0.734, p<0.01), and both systolic (r = 0.34, p<0.001) and diastolic (r = 0.21, p<0.001) standardized BP. WC percentile was less strongly correlated with standardized SBP (r = 0.255, p<0.01) and DBP (r = 0.175, p<0.01) than BMI.

Conclusions/Significance

The prevalence of elevated BP, notably systolic was significantly high among the Emirati children and adolescents in Abu Dhabi. High BP was strongly related to body weight, and appears more strongly associated with BMI than WC. Further studies are required to investigate the impact of childhood obesity on HTN.     

Standard Automated Perimetry versus Matrix Frequency Doubling Technology Perimetry in Subjects with Ocular Hypertension and Healthy Control Subjects

Background

To evaluate the relationship and agreement between standard automated perimetry (SAP) and Matrix frequency doubling technology (Matrix-FDT) in subjects with ocular hypertension and healthy control subjects.

Methods

Forty-four eyes of 44 ocular hypertensive subjects and 29 eyes of 29 healthy age-matched control subjects were included in this prospective study. All participants underwent complete ophthalmic examination, including slit-lamp biomicroscopy, intraocular pressure measurement, pachymetry, and dilated fundus examination, and showed reliable visual field tests. One randomly selected eye of each participant was examined with SAP (Swedish Interactive Threshold Algorithm [SITA] Standard 24-2 test) and Matrix-FDT (24-2 threshold test), in random order. Correlations between global indices (MD, PSD), regions (2 hemifields, 4 quadrants, 6 sectors) and 52 single field positions were analyzed using Spearman’s rank correlation coefficient.

Results

In both groups, mean deviation values of SAP and Matrix-FDT correlated significantly (OHT subjects: r = 0.47, p<0.005; healthy subjects: r = 0.68; p<0.001, respectively). Pattern standard deviation of SAP and Matrix-FDT showed no significant correlation in healthy subjects but correlated significantly in ocular hypertensive subjects (r = 0.45, p<0.005). In healthy subjects, a significant correlation between SAP and Matrix-FDT was shown in the supero-temporal and infero-temporal sectors of the disc (r = 0.40 and r = 0.38, p<0.05, respectively). In OHT subjects, supero-temporal, supero-nasal and nasal sectors correlated significantly (r = 0.49, 0.62 and 0.38, p≤0.01, respectively). The correlation pattern of individual visual field test locations appeared heterogeneous in both groups.

Conclusions

In both, ocular hypertensive and healthy subjects SAP and Matrix-FDT correlate well. In ocular hypertensive subjects, both techniques showed good correlation in the supero-temporal, supero-nasal, and nasal sectors of the disc. Poor agreement was found in the temporal, infero-temporal and infero-nasal disc sectors. This missing correlation might be related to early retinal nerve fiber layer damage in these regions of the disc, recognized by one of the visual field instruments.     

Gray Matter Abnormalities in Schizophrenia Patients with Tardive Dyskinesia: A Magnetic Resonance Imaging Voxel-Based Morphometry Study

Objective

The pathophysiological mechanism of TD remains unknown. All previous studies, using the region-of-interest method, focused on basal ganglion areas, were with inconsistent results. This whole-brain voxel-based morphometry (VBM) study investigate the grey matter abnormality of TD and its correlates with clinical ratings.

Method

High resolution T1-weighted brain volumetric MRI from 25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness-matched schizophrenia patients without TD (non-TD group), and 25 matched healthy subjects (NC group) were analyzed using a VBM approach. Clinical ratings included the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS).

Results

The TD group had significantly smaller total gray matter volumes than the NC group (p = 0.05). Compared to the non-TD group, the TD group had significantly higher PANSS negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller bilateral inferior frontal gyrus, which correlated negatively with the PANSS negative scores (r = −0.366, p<0.05); and smaller right superior frontal gyrus, which correlated negatively with AIMS scores (r = −0.399, p<0.001), and PANSS general score (r = −0.338, p<0.05).

Limitations

The cross-section design can’t separate the gray matter change to TD from the context of the illness of schizophrenia, although TD with more severe clinical psychopathology could be a phenotype.

Conclusions

The schizophrenia patients with TD had significantly reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right superior frontal gyrus, which correlated with severity of clinical symptoms and involuntary movement, respectively.     

A High Throughput Biochemical Fluorometric Method for Measuring Lipid Peroxidation in HDL

Current cell-based assays for determining the functional properties of high-density lipoproteins (HDL) have limitations. We report here the development of a new, robust fluorometric cell-free biochemical assay that measures HDL lipid peroxidation (HDLox) based on the oxidation of the fluorochrome Amplex Red. HDLox correlated with previously validated cell-based (r = 0.47, p<0.001) and cell-free assays (r = 0.46, p<0.001). HDLox distinguished dysfunctional HDL in established animal models of atherosclerosis and Human Immunodeficiency Virus (HIV) patients. Using an immunoaffinity method for capturing HDL, we demonstrate the utility of this novel assay for measuring HDLox in a high throughput format. Furthermore, HDLox correlated significantly with measures of cardiovascular diseases including carotid intima media thickness (r = 0.35, p<0.01) and subendocardial viability ratio (r = −0.21, p = 0.05) and physiological parameters such as metabolic and anthropometric parameters (p<0.05). In conclusion, we report the development of a new fluorometric method that offers a reproducible and rapid means for determining HDL function/quality that is suitable for high throughput implementation.     

Left Ventricular Mechanics in Repaired Tetralogy of Fallot with and without Pulmonary Valve Replacement: Analysis by Three-Dimensional Speckle Tracking Echocardiography

Background

Altered septal curvature and left ventricular (LV) geometry secondary to right ventricular (RV) dilation render two-dimensional assessment of LV mechanics difficult in repaired tetralogy of Fallot (TOF) patients. The novel three-dimensional (3D) speckle tracking echocardiography enables comprehensive evaluation of true 3D LV mechanics.

Methods and Results

Seventy-six patients aged 23.6±8.3 years, 55 with isolated repair (group I) and 21 with subsequent pulmonary valve replacement (group II), and 34 healthy controls were studied. Three-dimensional volume datasets were acquired for assessment of LV global and regional 3D strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction. A global performance index was calculated as (global 3D strain•twist gradient)/SDI. The septal curvature and LV eccentricity were determined from the mid-ventricular short-axis. Compared with controls, group I and II patients had significantly reduced LV global 3D strain, LV twist, twist gradient, septal curvature, and global performance index, and greater LV systolic and diastolic eccentricity and SDI (all p<0.05). All but the four apical LV segments in patients had reduced regional 3D strain compared with controls (all p<0.05). Septal curvature correlated with LV global 3D strain (r = 0.41, p<0.001), average septal strain (r = 0.38, p<0.001), twist (r = 0.32, p<0.001), twist gradient (r = 0.33, p<0.001), and global performance index (r = 0.43, p<0.001).

Conclusions

Adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist is related to reduced septal curvature in repaired TOF patients with and without pulmonary valve replacement.     

The Bioenergetic Status Relates to Dopamine Neuron Loss in Familial PD with PINK1 Mutations

Mutations in the PINK1 gene cause autosomal recessive familial Parkinson’s disease (PD). The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous (³¹P) and proton (¹H) 3-T magnetic resonance spectroscopic imaging (MRSI) in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6) compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA) positron emission tomography (PET). The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and β-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA K_i values correlated positively with MI (r = 0.879, p<0.001) and inversely with β-ATP (r = −0.784, p = 0.008) and GPC concentrations (r = −0.651, p = 0.030) in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.     

When Do We Really Need Coronary Calcium Scoring Prior to Contrast-Enhanced Coronary Computed Tomography Angiography? Analysis by Age,Gender and Coronary Risk Factors

Aims

To investigate the value of coronary calcium scoring (CCS) as a filter scan prior to coronary computed tomography angiography (CCTA).

Methods and Results

Between February 2008 and April 2011, 732 consecutive patients underwent clinically indicated CCTA. During this ‘control phase’, CCS was performed in all patients. In patients with CCS≥800, CCTA was not performed. During a subsequent ‘CCTA phase’ (May 2011–May 2012) another 200 consecutive patients underwent CCTA, and CCS was performed only in patients with increased probability for severe calcification according to age, gender and atherogenic risk factors. In patients where CCS was not performed, calcium scoring was performed in contrast-enhanced CCTA images. Significant associations were noted between CCS and age (r = 0.30, p<0.001) and coronary risk factors (χ² = 37.9; HR = 2.2; 95%CI = 1.7–2.9, p<0.001). Based on these associations, a ≤3% pre-test probability for CCS≥800 was observed for males <61 yrs. and females <79 yrs. According to these criteria, CCS was not performed in 106 of 200 (53%) patients during the ‘CCTA phase’, including 47 (42%) males and 59 (67%) females. This resulted in absolute radiation saving of ∼1 mSv in 75% of patients younger than 60 yrs. Of 106 patients where CCS was not performed, estimated calcium scoring was indeed <800 in 101 (95%) cases. Non-diagnostic image quality due to calcification was similar between the ‘control phase’ and the ‘CCTA’ group (0.25% versus 0.40%, p = NS).

Conclusion

The value of CCS as a filter for identification of a high calcium score is limited in younger patients with intermediate risk profile. Omitting CCS in such patients can contribute to further dose reduction with cardiac CT studies.     

Use of Liver Stiffness Measurement for Liver Resection Surgery: Correlation with Indocyanine Green Clearance Testing and Post-Operative Outcome

Background

Liver stiffness measurement (LSM) using transient elastography has recently become available for the assessment of liver fibrosis. Whether LSM can predict the functional liver reserve in patients undergoing liver resection is not certain.

Aim

To correlate liver stiffness measurement (LSM) with indocyanine green (ICG) clearance test and liver biochemistry, and to determine its usefulness in predicting postoperative outcomes in patients undergoing liver resection.

Patients and Methods

Transient elastography and ICG clearance test were performed pre-operatively in 44 patients with hepatocellular carcinoma. The LSM and ICG retention rate at 15 minutes (R15) were correlated with pre-operative factors and post-operative outcomes.

Results

There was significant correlation between ICG R15 and LSM. In patients with LSM ≥11 kPa vs <11 kPa, there was significantly higher ICG R15 (17.1% vs 10.0% respectively, p = 0.025). For patients with ICG R15≥10% compared to those <10%, there was significantly higher LSM (12.0 vs 7.6 kPa respectively, p = 0.015). Twenty-eight patients proceeded to resection. There was a significant correlation between LSM and the peak INR after liver resection (r = 0.426, p = 0.024). There was a significant correlation between ICG R15 and the post-operative peak AST level (r = −0.414, p = 0.029) and peak ALT level (r = −0.568, p = 0.002). The operative time was a significant independent factor associated with post-operative complications and peak INR.

Conclusion

LSM correlated well with ICG R15 in patients undergoing liver resection, and predicted early post-operative complications. Addition of LSM to ICG R15 testing may provide better prognostic information for patients undergoing resection.     

Evaluation of Anterior Segment Parameters and Possible Influencing Factors in Normal Subjects Using a Dual Scheimpflug Analyzer

Purpose

To investigate normal anterior segment parameters and analyze the possible influencing factors using a dual Scheimpflug system.

Setting

Department of Ophthalmology, Affiliated Sixth People''s Hospital Shanghai Jiao Tong University, Shanghai, China.

Design

A prospective observational case series.

Methods

A total of 153 normal subjects (153 eyes) were studied. The anterior segment parameters, including the central corneal thickness (CCT), anterior chamber depth (ACD), pupil diameter (PD), keratoconus prediction index (KPI), simulated keratometry (SimK) values, anterior instantaneous curvature (AIC), posterior axial curvature (PAC), corneal eccentricity, total corneal power (TCP), axial curvature (AC), total corneal wavefront (TCW), high order aberration (HOA), and spherical aberration (SA), were determined using a dual Scheimpflug analyzer.

Results

The CCT and ACD were both negatively correlated with age (r = −0.203, p = 0.012; r = −0.589, p<0.001). There was no significant difference in the refractive indices of AIC and SimK. Compared with the negative correlation of HOA and SA (r = −0.358, p<0.001), a positive correlation was found between TCW and HOA (r = 0.561, p<0.001). Unlike the decreased tendency of AC, the TCP increased gradually from the center to the periphery in the central 8 mm diameter. TCP showed a significant correlation with AC in the analyzed area.

Conclusions

AIC and SimK provide different information in clinic, but the refractive indices of them showed no difference in this healthy study population, and age should be considered when using CCT and ACD values.     

Visual Acuity Testing: Feedback Affects Neither Outcome nor Reproducibility,but Leaves Participants Happier

Assessment of visual acuity is a well standardized procedure at least for expert opinions and clinical trials. It is often recommended not giving patients feedback on the correctness of their responses. As this viewpoint has not been quantitatively examined so far, we quantitatively assessed possible effects of feedback on visual acuity testing. In 40 normal participants we presented Landolt Cs in 8 orientations using the automated Freiburg Acuity Test (FrACT, <michaelbach.de/fract. Over a run comprising 24 trials, the acuity threshold was measured with an adaptive staircase procedure. In an ABCDDCBA scheme, trial-by-trial feedback was provided in 2 x 4 conditions: (A) no feedback, (B) acoustic signals indicating correctness, (C)visual indication of correct orientation, and (D) a combination of (B) and (C). After each run the participants judged comfort. Main outcome measures were absolute visual acuity (logMAR), its test-retest agreement (limits of agreement) and participants’ comfort estimates on a 5-step symmetric Likert scale. Feedback influenced acuity outcome significantly (p = 0.02), but with a tiny effect size: 0.02 logMAR poorer acuity for (D) compared to (A), even weaker effects for (B) and (C). Test-retest agreement was high (limits of agreement: ± 1.0 lines) and did not depend on feedback (p>0.5). The comfort ranking clearly differed, by 2 steps on the Likert scale: the condition (A)–no feedback–was on average “slightly uncomfortable”, the other three conditions were “slightly comfortable” (p<0.0001). Feedback affected neither reproducibility nor the acuity outcome to any relevant extent. The participants, however, reported markedly greater comfort with any kind of feedback. We conclude that systematic feedback (as implemented in FrACT) offers nothing but advantages for routine use.     

Serum Glycated Albumin to Guide the Diagnosis of Diabetes Mellitus

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p<0.001), serum albumin (r = –0.1179, age-adjusted p = 0.001), body mass index (r = -0.24, age-adjusted p<0.001), waist circumference (r = -0.16, age-adjusted p<0.001), and plasma GA (r = 0.999, p<0.001), but was unaffected by diet (p = 0.8). Using serum GA at 15% for diagnosis of diabetes, the sensitivity, specificity, and area under the receiver-operating characteristic curve were 74%, 85%, and 0.86, respectively. Applying a fasting plasma glucose (FPG) value of < 100 mg/dL to exclude diabetes and of ≥ 126 mg/dL to diagnose diabetes, 14.4% of the study population require an OGTT (OGTT%) with a sensitivity of 78.8% and a specificity of 100%. When serum GA value of 14% and 17% were used to exclude and diagnose diabetes, respectively, the sensitivity improved to 83.3%, with a slightly decrease in specificity (98.2%), but a significant increase in OGTT% (35%). Using combined FPG and serum GA cutoff values (FPG < 100 mg/dL plus serum GA < 15% to exclude diabetes and FPG ≥ 126 mg/dL or serum GA ≥ 17% to diagnose diabetes), the OGTT% was reduced to 22.5% and the sensitivity increased to 85.6% with no change in specificity (98.2%). In the diagnosis of diabetes, serum GA measurements can be used to determine the need of an OGTT.     

Follow-Up of Thrombin Generation after Prostate Cancer Surgery: Global Test for Increased Hypercoagulability

Recent studies provided evidence that evaluation of thrombin generation identifies patients at thrombotic risk. Thrombin generation has a central role in hemorrhage control and vascular occlusion and its measurement provides new metrics of these processes providing sufficient evaluation of an individual’s hemostatic competence and response to anticoagulant therapy. The objective of the study is to assess a new measure of hypercoagulability that predisposes to venous thromboembolism in the postoperative period after radical prostatectomy. Pre- (day-1) and postoperative (hour 1, day 6, month 1 and 10) blood samples of 24 patients were tested for plasma thrombin generation (peak thrombin), routine hematology and hemostasis. Patients received low molecular weight heparin for thromboprophylaxis. Peak thrombin levels were higher in patients compared to controls at baseline (p<0.001), and elevated further in the early postoperative period (p<0.001). Longer general anesthesia and high body mass index were associated with increased thrombin generation after surgery (p = 0.024 and p = 0.040). D dimer and fibrinogen levels were higher after radical prostatectomy (p = 0.001 and p<0.001). Conventional clotting tests remained within the reference range. Our study contributed to the cognition of the hypercoagulable state in cancer patients undergoing pelvic surgery and revealed the course of thrombin generation after radical prostatectomy. Whilst it is unsurprising that thrombin generation increases after tissue trauma, further evaluation of this condition during the postoperative period would lead urologists to an international and well-supported consensus regarding thromboprophylaxis in order to provide better clinical outcome. Considering the routine evaluation of procoagulant activity and extending prophylactic anticoagulant therapy accordingly may potentially prevent late thrombotic events.     

Prevalence and Outcomes of Cataract Surgery in Adult Rural Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye Study

Purpose

To investigate the prevalence and visual acuity (VA) outcomes of cataract surgery in adults of the Bai Nationality populations in rural China.

Methods

We conducted a population-based cross-sectional survey (from randomly selected block groups) of Chinese Bai Nationality aged ≥50 years in southwestern China. Presenting visual acuity (PVA), best corrected visual acuity (BCVA) were recorded and a detailed eye examination was carried out. For all aphakic and pseudophakic subjects identified, information on the date, setting, type, and complications of cataract surgery were recorded. In eyes with VA <20/63, the principal cause of visual impairment was identified.

Results

Of 2133 (77.8% of 2742) subjects, 99 people (129 eyes) had undergone cataract surgery. The prevalence of cataract surgery was 4.6%. Surgical coverage among those with PVA <20/200 in both eyes because of cataract was 52.8%. Unoperated cataract was associated with older age. The main barrier to cataract surgery was lack of awareness and knowledge, cost, and fear. Among the 129 cataract-operated eyes, 22.5% had PVA of ≥20/32, 25.6% had PVA of 20/40 to 20/63, 23.3% had PVA <20/63 to 20/200, and 28.7% had PVA<20/200. With BCVA, the percentages were 42.6%, 23.3%, 10.9%, and 23.3%, respectively. Aphakia (odds ratio [OR], 8.49; P<0.001) and no education (OR, 10.18; P = 0.001) or less education (OR, 6.49; P = 0.014) were significantly associated with postoperative visual impairment defined by PVA, while aphakia (OR, 8.49; P<0.001) and female gender (OR, 4.19; P = 0.004) were significantly associated with postoperative visual impairment by BCVA. The main causes of postoperative visual impairment were refractive error, retinal disorders and glaucoma.

Conclusions

Half of those with bilateral visual impairment or blindness because of cataract remain in need of cataract surgery in Bai population. Surgical uptake and visual outcomes should be further improved in the future.     

Cross-Sectional Comparison of Small Animal [18F]-Florbetaben Amyloid-PET between Transgenic AD Mouse Models

We aimed to compare [¹⁸F]-florbetaben PET imaging in four transgenic mouse strains modelling Alzheimer’s disease (AD), with the main focus on APPswe/PS2 mice and C57Bl/6 mice serving as controls (WT). A consistent PET protocol (N = 82 PET scans) was used, with cortical standardized uptake value ratio (SUVR) relative to cerebellum as the endpoint. We correlated methoxy-X04 staining of β-amyloid with PET results, and undertook ex vivo autoradiography for further validation of a partial volume effect correction (PVEC) of PET data. The SUVR in APPswe/PS2 increased from 0.95±0.04 at five months (N = 5) and 1.04±0.03 (p<0.05) at eight months (N = 7) to 1.07±0.04 (p<0.005) at ten months (N = 6), 1.28±0.06 (p<0.001) at 16 months (N = 6) and 1.39±0.09 (p<0.001) at 19 months (N = 6). SUVR was 0.95±0.03 in WT mice of all ages (N = 22). In APPswe/PS1G384A mice, the SUVR was 0.93/0.98 at five months (N = 2) and 1.11 at 16 months (N = 1). In APPswe/PS1dE9 mice, the SUVR declined from 0.96/0.96 at 12 months (N = 2) to 0.91/0.92 at 24 months (N = 2), due to β-amyloid plaques in cerebellum. PVEC reduced the discrepancy between SUVR-PET and autoradiography from −22% to +2% and increased the differences between young and aged transgenic animals. SUVR and plaque load correlated highly between strains for uncorrected (R = 0.94, p<0.001) and PVE-corrected (R = 0.95, p<0.001) data. We find that APPswe/PS2 mice may be optimal for longitudinal amyloid-PET monitoring in planned interventions studies.     

Mycobacterium ulcerans in the Elderly: More Severe Disease and Suboptimal Outcomes

Background

The clinical presentation of M. ulcerans disease and the safety and effectiveness of treatment may differ in elderly compared with younger populations related to relative immune defficiencies, co-morbidities and drug interactions. However, elderly populations with M. ulcerans disease have not been comprehensively studied.

Methodology/Principal Findings

A retrospective analysis was performed on an observational cohort of all confirmed M. ulcerans cases managed at Barwon Health from 1/1/1998-31/12/2014. The cohort included 327 patients; 131(40.0%) ≥65 years and 196(60.0%) <65 years of age. Patients ≥65 years had a shorter median duration of symptoms prior to diagnosis (p<0.01), a higher proportion with diabetes (p<0.001) and immune suppression (p<0.001), and were more likely to have lesions that were multiple (OR 4.67, 95% CI 1.78–12.31, p<0.001) and WHO category 3 (OR 4.59, 95% CI 1.98–10.59, p<0.001). Antibiotic complications occurred in 69(24.3%) treatment episodes at an increased incidence in those aged ≥65 years (OR 5.29, 95% CI 2.81–9.98, p<0.001). There were 4(1.2%) deaths, with significantly more in the age-group ≥65 years (4 compared with 0 deaths, p = 0.01). The overall treatment success rate was 92.2%. For the age-group ≥65 years there was a reduced rate of treatment success overall (OR 0.34, 95% CI 0.14–0.80, p = <0.01) and when surgery was used alone (OR 0.21, 95% CI 0.06–0.76, p<0.01). Patients ≥65 years were more likely to have a paradoxical reaction (OR 2.06, 95% CI 1.17–3.62, p = 0.01).

Conclusions/Significance

Elderly patients comprise a significant proportion of M. ulcerans disease patients in Australian populations and present with more severe and advanced disease forms. Currently recommended treatments are associated with increased toxicity and reduced effectiveness in elderly populations. Increased efforts are required to diagnose M. ulcerans earlier in elderly populations, and research is urgently required to develop more effective and less toxic treatments for this age-group.     

Platelet Turnover in Stable Coronary Artery Disease – Influence of Thrombopoietin and Low-Grade Inflammation

Background

Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD). The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown.

Aim

To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency.

Methods

We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio) were determined using automated flow cytometry (Sysmex XE-2100). Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6.

Results

We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r = 0.61–0.99, p<0.0001). Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r = −0.17–−0.25, p<0.0001). Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p = 0.03) and in smokers (p = 0.003). Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r = 0.10, p = 0.03) and thrombopoietin (r = 0.16, p<0.001). Also interleukin-6 correlated with thrombopoietin (r = 0.10, p = 0.02).

Conclusion

In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a substantial impact on platelet turnover parameters.