Comparing Five Criteria for Evaluating Glaucomatous Visual Fields

This study aimed to compare the statistical power of structural and visual field (VF) outcomes for randomized clinical trials (RCTs) in glaucoma. Analysis of retrospectively collected data. Eighty-two patients with glaucoma were recruited to a test-retest study, during which up to 10 24-2 Swedish Interactive Thresholding Algorithm (SITA) Standard VF and circumpapillary retinal nerve fiber layer (cpRNFL) Spectralis OCT scans were collected in separate sessions over 3 months. Eyes with at least 3 sessions with a reliable VF (false-positives < 15%) and cpRNFL scan (quality index ≥ 25 dB) were selected (127 eyes, 68 patients) to model the test-retest variability and the structural floor effect. These estimates were combined with a published realistic structure-function progression model from the United Kingdom Glaucoma Treatment Study to simulate longitudinal RCTs (30% neuroprotective effect). Simulations only included data from eyes with early to moderate VF loss (mean deviation [MD], ≥-10 dB, 107 eyes, 65 patients). Simulations were repeated 5000 times to estimate sample size requirements to detect a significant difference (P < 0.05) in the rate of change of MD and average cpRNFL thickness, estimated with a linear mixed-effects model. We also tested the power of a significant outcome with either metric (P < 0.025). A supplementary analysis was performed including eyes with early VF loss only (MD ≥ -6 dB). Sample size at 80% power for the linear rate of MD, cpRNFL, and their combination. At 80% power, the required sample size (patients [95% confidence interval]) was 38% smaller for the MD rate (292 [300-283]) than the cpRNFL rate (470 [481-459]). The sample size for the combined outcome was only marginally smaller than the MD alone (275 [283-268]). The supplementary analysis on eyes with early VF loss showed similar results. Using realistic modeling of structure-function progression and test-retest data, MD progression showed higher statistical power cpRFNL as an outcome measure for clinical trials. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To validate a method for visual field (VF) progression analysis, called ANSWERS (Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement), which takes into account increasing measurement variability as glaucoma progresses and spatial correlation among test locations. ANSWERS outputs both a global index of progression and a pointwise estimate of rate of change at each VF location. ANSWERS was compared with linear regression of mean deviation (MD) and permutation of pointwise linear regression (PoPLR). Visual field series of up to 2 years from the United Kingdom Glaucoma Treatment Study were used. This consists of 9104 Swedish Interactive Thresholding Algorithm Standard 24-2 VFs. ANSWERS and PoPLR rate of change were used to predict the VF at the next visit using subseries that were within 7, 13, 18, or 22 months from the baseline. The comparison was carried out on the statistical sensitivity, specificity, and accuracy of predicting future VF. Across all subseries, statistical sensitivity of ANSWERS in detecting VF deterioration was significantly better than the linear regression of MD and PoPLR, especially in short time series. Prediction accuracy of ANSWERS was better than PoPLR at all series lengths, and the improvement was particularly marked in shorter series. Seventy-five percent of VF series were better predicted by ANSWERS compared with PoPLR. The average prediction error of ANSWERS was 15% lower than that of PoPLR. ANSWERS is more sensitive to detect VF progression and predicts future VF loss better than linear regression of MD and PoPLR, especially over short observation periods. (http://www.isrctn.com number, ISRCTN96423140.).

To investigate the association of magnetic resonance imaging (MRI) of anterior optic pathway with glaucomatous visual field damage and optic disc cupping. Twenty-three healthy volunteers (controls) and 31 glaucoma patients (14 with primary open angle glaucoma and 17 with normal tension glaucoma) were enrolled. All the participants showed no abnormal signs in their intracranial space and optic tract causing optic nerve atrophy and visual field defect, as confirmed by MRI. Multislice T1-weighted spin-echo imaging was performed in the sagittal plane followed by the coronal plane. MRI enabled the evaluation of the diameter of the optic nerve located in the retro-bulb space and the height of the optic chiasm in an observer-masked fashion. The MRI data were compared with the mean deviation (MD) score of the full threshold static visual field test and the optic cup-disc ratio (C/D ratio). The optic nerve diameter was significantly smaller in glaucoma patients (2.25 +/- 0.33 mm) than in controls (2.47 +/- 0.24 mm) and the height of the optic chiasm was significantly shorter in glaucoma patients (2.12 +/- 0.37 mm) than in controls (2.77 +/- 0.36 mm). The optic nerve diameter showed significant correlation with MD score (r = 0.547, P = 0.001) and C/D ratio (r = 0.407, P = 0.009). These correlations are similar to that between MD score and C/D ratio (r = 0.490, P = 0.001). The height of the optic chiasm showed significant correlation with MD score (r = 0.503, P = 0.01) and low correlation with C/D ratio (r = 0.339, P = 0.113). Glaucoma affects the anterior visual pathway anterogradely at least up to the optic chiasm, and these morphologic changes in the anterior visual pathway are correlated with glaucomatous optic nerve damage. MRI of the anterior visual pathway may be a good tool for evaluating glaucomatous damage objectively.

To predict the magnitude of functional damage [mean deviation (MD) on visual field examination] and structural damage [retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness on spectral domain optical coherence tomography] in glaucoma from monocular pupillary light response measurements using automated pupillography. In total, 59 subjects (118 eyes) with either a confirmed or suspected diagnosis of glaucoma underwent automated pupillography, along with visual fields and spectral domain optical coherence tomography examinations. Association between pupillary light response measurements of each eye [amplitude of constriction, latency of onset of constriction (Loc), latency of maximal constriction (Lmaxc), velocity of constriction and velocity of redilation] and corresponding MD, average RNFL, and average GCC measurements were evaluated using univariate and multivariate regression analysis after accounting for the multicollinearity. Goodness of fit of the multivariate models was evaluated using coefficient of determination (R). Multivariate regression models that contained Loc and Lmaxc showed the best association with MD (R of 0.30), average RNFL thickness (R=0.18) and average GCC thickness (R=0.26). The formula that best predicts the MD could be described as: MD=-14.06-0.15×Loc+0.06×Lmaxc. The formula that best predicts the average RNFL thickness could be described as: Average RNFL thickness=67.18-0.22×Loc+0.09×Lmaxc. Glaucomatous damage as estimated by MD, RNFL, and GCC thickness measurements were best predicted by the latency parameters (Loc and Lmaxc) of pupillography. Worsening of glaucomatous damage resulted in a delayed onset of pupillary constriction and a decreased Lmaxc.

In temperate regions rotavirus diarrhea is a disease of the cooler months of the year, but little is known about its patterns in the summer. We report on the first year of national surveillance of rotavirus, during which we actively investigated patterns of summer activity. We obtained data on rotavirus testing from 85 laboratories in 48 states, conducted a survey of their testing practices and retested for confirmation positive specimens from laboratories reporting high rates of positivity during the summer. During 1989 participating laboratories reported 4011 specimens tested for rotavirus during July and August, of which 436 (11%) were said to be positive. Most laboratories reported low rates of positivity during these months (median percent positive, 3), but five had very high rates of summer positivity (> 30%). These five laboratories were geographically separated, and neighboring laboratories showed little rotavirus activity. Positive specimens submitted by four of these centers with high rates of summer rotavirus could not be confirmed. A survey of laboratory methods found one commercial assay (TestPack) and two laboratory practices (failure to use controls and involvement of more than six technicians in the testing process) to be associated with high rates of summer positivity. Moderate rates of positivity (11 to 30%) were fond frequently in the southwest during July and August; reference testing of specimens from these laboratories confirmed positivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectral-Domain OCT: Helping the Clinician Diagnose Glaucoma: A Report by the American Academy of Ophthalmology

Objective: To explore the allergen map of patients with allergic diseases in northwest China, to investigate the distribution characteristics of serum specific Immunoglobulin E (sIgE) in different ages, genders, diseases and the sensitization patterns of allergens. Methods: This study is a cross-sectional study, a total of 1 161 patients with confirmed respiratory allergic diseases were selected retrospectively from outpatient or inpatient department of Gansu Provincial People's Hospital, Gansu Provincial Maternity and Child Care Hospital, General Hospital of Ningxia Medical University, Yinchuan Maternal and Child Health Care Hospital, Xijing Hospital, Air Force Military Medical University and Tumor Hospital of Inner Mongolia Autonomous Region from June 2019 to October 2022. HAIKE ALLEOS 2000 fluorescent magnetic particle chemiluminescence method was used to quantify their serum for 12 inhaled allergen-specific IgE. Chi square test or Fisher's exact test were used for comparison between count data groups (Bonferroni correction was used for further pairwise comparison in multiple groups, two-sided P<0.05/3=0.017 considered that the difference was statistically significant). Pearson correlation analysis was used for correlation of continuous numerical variables. Results: The positive detection rate of sIgE in 1 161 patients was 66.8%(776/1 161). The three highest positive rate of inhaled allergen were mugwort(599/1 161, 51.6%), French chrysanthemum(565/1 161, 48.7%) and dandelion(412/1 161, 35.5%). In different age groups, the highest positive rate of sIgE was 7-18 age group(379/513, 73.9%) while the lowest positive rate was 4-6 age group(222/370, 60.0%), the difference between groups was statistically significant(χ2=21.177, P<0.001). The sensitization peak of mugwort, French chrysanthemum, plantain, timothy, birch, dermatophagoides pteronyssinus, dermatophagoides farinae, cat epithelium, dog epithelium and German cockroach appeared in 7-18 age group. In different disease groups, the highest positive rate of sIgE was allergic rhinitis with asthma group (500/717, 69.7%) while the lowest positive rate was asthma group (76/144, 52.8%), the difference between groups was statistically significant(χ2=15.563, P<0.001). In different gender groups, the positive rate of sIgE in male (503/711, 70.7%) was higher than in female (273/450, 60.7%), the difference between groups was statistically significant(χ2=12.630, P<0.001). The multiple-sensitization rate was 86.9%(674/776) and the double-sensitization rate was 16.8%(130/776) in sIgE positive patients. Pearson correlation results showed that there was an extremely strong correlation between dandelion and French chrysanthemum(r=0.93,P<0.001). There was a strong correlation between mugwort and French chrysanthemum(r=0.64,P<0.001). In the co-sensitization analysis, the number of patients sensitized by mugwort, French chrysanthemum, dandelion, plantain and timothy accounted for 25.2%(170/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum and dandelion accounted for 58.3%(393/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum, dandelion and plantain accounted for 35.6%(240/674) of the total number of multiple sensitization. Conclusion: Mugwort, French chrysanthemum, dandelion are the major inhaled allergens in northwest China. The positive rate of sIgE was different in different ages, diseases and genders. The multiple-sensitization rate of allergen was high and there was a certain positive correlation between pollen allergen-specific IgE pairwise, suggesting that there may exist co-sensitization or cross-reactions among allergens.

To determine whether topographical measurements of the parapapillary region analyzed by machine learning classifiers can detect early to moderate glaucoma better than similarly processed measurements obtained within the disc margin and to improve methods for optimization of machine learning classifier feature selection. One eye of each of 95 patients with early to moderate glaucomatous visual field damage and of each of 135 normal subjects older than 40 years participating in the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) were included. Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Dossenheim, Germany) mean height contour was measured in 36 equal sectors, both along the disc margin and in the parapapillary region (at a mean contour line radius of 1.7 mm). Each sector was evaluated individually and in combination with other sectors. Gaussian support vector machine (SVM) learning classifiers were used to interpret HRT sector measurements along the disc margin and in the parapapillary region, to differentiate between eyes with normal and glaucomatous visual fields and to compare the results with global and regional HRT parameter measurements. The area under the receiver operating characteristic (ROC) curve was used to measure diagnostic performance of the HRT parameters and to evaluate the cross-validation strategies and forward selection and backward elimination optimization techniques that were used to generate the reduced feature sets. The area under the ROC curve for mean height contour of the 36 sectors along the disc margin was larger than that for the mean height contour in the parapapillary region (0.97 and 0.85, respectively). Of the 36 individual sectors along the disc margin, those in the inferior region between 240 degrees and 300 degrees, had the largest area under the ROC curve (0.85-0.91). With SVM Gaussian techniques, the regional parameters showed the best ability to discriminate between normal eyes and eyes with glaucomatous visual field damage, followed by the global parameters, mean height contour measures along the disc margin, and mean height contour measures in the parapapillary region. The area under the ROC curve was 0.98, 0.94, 0.93, and 0.85, respectively. Cross-validation and optimization techniques demonstrated that good discrimination (99% of peak area under the ROC curve) can be obtained with a reduced number of HRT parameters. Mean height contour measurements along the disc margin discriminated between normal and glaucomatous eyes better than measurements obtained in the parapapillary region.

Diagnosis of mouse hepatitis virus contamination in mouse population by using nude mice and RT-PCR

A new rat model of recurrent pulmonary aspergillosis using cyclophosphamide (CPM) for re-institution of immunosuppression was established. The recurrence induced by CPM was rapid and pulmonary lesions were uniform in all animals. It is therefore considered to be a good model for evaluation of the mechanisms of recurrence and methods of early diagnosis by antigen detection in sera and urine. Galactomannan antigen of aspergilli in sera was examined by PASTOREX Aspergillus, and a very low positive rate was observed instead of the of severe pulmonary infection confirmed by histopathological study. However, antigen in urine detected by immunoblotting showed a relatively high positive rate from the early stage of the recurrence. Based on these findings, it can be concluded that the recognition of antigenuria is useful for early diagnosis of Aspergillus infection.

Antigenic domain 1 (AD-1), located between amino acids 608 and 625 of human cytomegalovirus (CMV) gB protein, is the major domain recognized by neutralizing antibodies. Amino acids 552 to 630 are essential for the binding of neutralizing antibodies. We developed an enzyme-linked immunosorbent assay (ELISA) to detect antibodies against a fusion protein containing amino acid residues 549 to 644 of the gB polypeptide and maltose binding protein (MBP). Of 180 seropositive samples, 106 (58.9%) showed positive immuno-reactivity against the fusion protein. None of the seronegative samples reacted with the fusion protein. Among 57 seropositive individuals typed for HLA, subjects with HLA-DR9 had a higher positive rate against the fusion protein (13/14=92.9%) than those without HLA-DR9 (25/43=58.1%). In addition, subjects with HLA-DR15 had a lower positive rate against the fusion protein (7/16=43.3%) than those without HLA-DR15 (31/41=75.6%). Mean OD values of HLA-DR15-positive individuals were significantly lower than those of HLA-DR15-negative individuals. Thus, among CMV-infected individuals, HLA-DR9 may be associated with responders for neutralizing antibodies and HLA-DR15 may be associated with non/low-responders.

To investigate the hepatitis C virus (HCV) infection rate among general population in Jiangsu province and to analyze the main risk factors for HCV infection. Subjects in 3 counties were surveyed by stratified cluster random sampling in the National Major Science and Technology Projects demonstration area in Jiangsu province. Interview was carried out with uniformly- designed questionnaires. Blood samples were collected and anti-HCV tested. Data were analysed under SPSS 13.0. Case-control study was conducted on two groups with subjects under 1:4 matching by sex, age, village of residence and status of HCV infection. Cox's proportional hazards regression analysis was then performed to analyze the risk factors for HCV infection. The positive rate of anti-HCV was higher in females (0.965%, 95%CI:0.899%-1.035%) than in males (0.572%, 95%CI:0.517%-0.632%). Significant differences were noticed among the positive rates of anti-HCV in the three counties (0.131%, 95%CI:0.103%-0.164%;0.316%, 95%CI: 0.268%-0.370%; 2.173% , 95% CI:2.039%-2.315% , respectively). Peak prevalence of anti-HCV (1.577%, 95%CI:1.425%-1.740%) was observed among persons at 50-59 years of age. Bottom rate (0.161%, 95%CI:0.125%-0.204%) was observed below 30 years of age. High anti-HCV positive rate was detected in people with lower education background or belonged to 'floating population'. Factors as having histories of hospitalization (OR = 3.049, 95% CI:1.322-7.036), blood transfusion (OR = 14.319, 95%CI:2.318-88.459) or sharing razor (OR = 3.604, 95%CI:1.096-11.851) were risk factors of HCV infection in the area with the lowest anti-HCV positive rate. In another county, factor as having histories of 'blood products transfusion' (OR = 7.202, 95% CI:1.170-44.310) appeared important while in the third county, having history of 'blood donation' (OR = 7.496, 95%CI:6.121- 9.180); 'blood transfusion' (OR = 2.305, 95%CI:1.578-3.369) and 'invasive physical examination' (OR = 1.258, 95% CI:1.021-1.549) appeared to be important. Age seemed a risk factor for HCV infection. "Sharing razor" was a specifically important risk factor among the 30- year-olds. "Having received acupuncture" was noticed a risk factor only among people at 50-59 years of age while "Having received invasive physical examination" was important in the 50-59 and 60-69 year-olds. High anti-HCV positive rate was observed in people at middle of aged population, as well as in those with poor education or under 'floating'. Unsafe blood donation or having received blood-product transfusion might be the risk factors in the last decades. Factors as sharing razor, having received acupuncture or invasive examination might be specifically risky in different populations.

US blood centers can screen female plateletpheresis donors with a history of one or more pregnancies for both Class I and Class II anti-HLA antibodies using one of two platforms. One is a flow-based assay that yields a quantitative result and the other an enzyme-linked immunosorbent assay (ELISA) that yields either a positive or a negative result (above or below cutoff). The results of HLA antibody screening tests were analyzed by donor ABO group. Results from large and small American blood collection centers using both platforms were analyzed. Positivity rates were compared by chi-square test and the results stratified by parity using the Mann-Whitney test. No differences in parity were noted among donors of different ABO groups, but a significantly higher rate of HLA antibody positivity was observed among group O donors for the ELISA (31% of group O donors vs. 21% of non-group O donors, p < 0.0001). The higher rate of positivity was primarily due to Class I reactivity. This difference in antibody frequency was not observed at centers using the flow-based assay. Centers using the ELISA may have a higher rate of permanent deferral from plateletpheresis donation among group O female donors. Although the reasons for the higher rate of reactivity on Class I ELISA testing are unknown, this could result from test system characteristics or differences in group O donor antibody strength or specificity.

This study analyzed the prevalence and antibiotic susceptibility of urogenital Ureaplasma urealyticum and Mycoplasma hominis isolated in Xi'an, China. A total of 2161 individuals from 2011 to 2015 were included, and antibiotic susceptibility tests were performed by using the Mycoplasma IST kit. Of the individuals studied, 1018 (47.11%) were identified to be positive for urogenital mycoplasmas. The single U. urealyticum, single M. hominis, and dual U. urealyticum and M. hominis infections accounted for 772 (75.83%), 66 (6.48%), and 180 (17.68%), respectively. The total positive rate was higher in females than in males (58.76% vs. 28.86%, p < 0.001). The highest total positive rate (48.88%) was observed in individuals aged 25 years to 30years. In symptomatic and asymptomatic individuals, the positive rates were both higher in females than in males (67.36% vs. 31.02%, p < 0.001 and 42.58% vs. 7.69%, p < 0.001, respectively) and individuals aged 25 years to 30years, and those aged 30 years to 35years had the highest positive rates (54.35 and 57.14%, respectively). The U. urealyticum and M. hominis identified from single or dual infections displayed low resistance rates to josamycin, doxycycline, and minocycline (<10%) in both the symptomatic and asymptomatic groups. These results suggest that females and individuals with symptoms and younger age had higher mycoplasma infection rates and that josamycin, doxycycline, and minocycline may be recommended for the clinical treatment of patients infected with urogenital mycoplasmas, irrespective of the symptoms.

Objective To evaluate the performance of three antibody kits for novel coronavirus (SARS-CoV-2) and to investigate the feasibility and advantages of them in clinical application. Methods A total of 104 patients who were admitted to Guangzhou Eighth People's Hospital with COVID-19 from January to February 2020 were selected as research group. Fifty-one healthy subjects were selected during the same period as negative control group. Serum antibodies (IgM/IgG) against SARS-CoV-2 were detected using two kinds of colloidal gold kits (A and B kits) and one chemiluminescence kit (C kit). The positive rates of SARS-CoV-2 nucleic acid in different samples from patients with COVID-19 were retrospectively analyzed. Results The clinical sensitivity of A kit to detect SARS-CoV-2-specific IgM and IgG was 77.88% (81/104) and 65.38% (68/104), respectively, and the clinical specificity was 70.59% (36/51) and 100.00% (51/51). However, the false positive rate in IgM detection was as high as 29.41% (15/51). The sensitivity of B kit to test total antibodies to SARS-CoV-2 was 63.46% (66/104), and the clinical specificity was 94.12% (48/51). The clinical sensitivity of C kit to detect SARS-CoV-2-specific IgM and IgG were respectively 31.73% (33/104) and 64.42% (67/104), and the clinical specificity were both 98.04% (50/51). There was a moderate correlation between the detection results of two colloidal gold kits and the chemiluminescence kit with the Kappa values of 0.462 and 0.587 (Z=6.157, P<0.01; Z=7.345, P<0.01). C kit had the highest positive detection rate for IgG, and would be more reliable to be used for IgG detection in COVID-19 patients 14 d after onset. The total positive detection rate of nucleic acid in all types of samples was 63.46% (66/104). The highest positive detection rate was in throat swabs or sputum samples, followed by those in blood samples and anal swabs. No viral nucleic acid was detected in urine samples for the time being. Conclusions SARS-CoV-2-specific antibodies could be detected in the early or late stage of COVID-19. The method of antibody detection has the advantages of shorter detection time, simple operation and high biological safety, indicating that it could be used as a supplementary or auxiliary detection for the diagnosis of suspected COVID-19 cases with negative nucleic acid test results. The chemiluminescence kit has good sensitivity and specificity, and is well recommended for clinical laboratories. Key words: SARS-CoV-2; Chemiluminescence immunoassay; Colloidal gold immunoaasay; Nucleic acid detection; Performance evaluation; Clinical application