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This prospective study aimed to compare vascular parameters (endothelin-1 [ET-1] blood levels, laser Doppler imaging [LDI] of distal phalanxes, and nailfold capillaroscopy) between open-angle glaucoma patients with low- and high-tension optic disc hemorrhages (LTDH and HTDH, respectively). The 33 enrolled patients (mean age, 62.3 ± 13 years) were classified as LTDH or HTDH if they presented at the time of DH detection an intraocular pressure (IOP) < 16 mmHg or ≥ 16 mmHg, respectively. Demographic and ophthalmological data, ET-1 concentrations, LDI (before and 1, 10, and 20 min after cold stimulation), and nailfold capillaroscopy findings were evaluated. The ET-1 blood level was 65% higher in the LTDH (2.27 ± 1.46 pg/ml) than in the HTDH (1.37 ± 0.57 pg/ml; p = 0.03) group. Moreover, there was a statistically significant negative correlation between ET-1 blood concentration and IOP at the time of DH detection (r = -0.45, p = 0.02). Blood flow measurements 10 and 20 min after cold stimulation were lower in the LTDH group than in the HTDH group (p < 0.01). Patients developing DH with lower IOPs have higher ET-1 blood levels and more peripheral vascular dysfunction as estimated by LDI than those with higher IOPs. These findings suggest that distinct underlying mechanisms may be involved in patients developing DH within different IOP ranges., (© 2023. The Author(s).)

This unicentric randomized clinical trial was designed to compare the surgical outcomes of mitomycin C-enhanced trabeculectomy (MMC-TRAB) with and without subtenon triamcinolone acetonide (TAAC) injection in patients with non-inflammatory glaucomas. This trial is registered at the Brazilian Registry of Clinical Trials (ReBEC) under the register number RBR-53f8nh. Consecutive non-inflammatory glaucoma patients requiring surgical intervention were randomized into two groups. In the control group, eyes underwent standard MMC-TRAB, while in the intervention group, besides the standard MMC-TRAB, these eyes also received a subtenon TAAC injection (4mg) close to the bleb site at the end of the surgery. The main outcomes of the study were surgical success rates, intraocular pressure (IOP) and number of medications at all timepoints. Success was defined as IOP ≤ 15 mmHg and subdivided in complete or qualified according to the need of medication. A total of 75 eyes of 63 different patients were included (intervention group = 39 eyes; control group = 36 eyes). There was no difference between groups at baseline (p>0.11). Multivariable regression analysis indicated that IOP levels were significantly lower in the intervention group at 18 and 24 months of follow-up when number of medications was considered as a covariate (P<0.001). Complete success rates were higher in the intervention group at 06 (90.9% vs 68.7%; p = 0.03), 12 (87.2% vs 66.7%; p = 0.02) and 18 months (87.2% vs 66.7%; p = 0.02). Additionally, although success rates at 24 months were higher in the intervention group (82.0% vs 66.7%; p = 0.09), this difference did not reach statistical significance. Qualified success rates did not significantly differ between groups at all timepoints. In conclusion, this study found significantly lower IOPs levels at 18 and 24 months of follow-up and higher complete success rates until 18 months of follow-up, with the use of subtenon TAAC as an adjuvant to standard MMC-TRABs in non-inflammatory glaucoma patients., Competing Interests: The authors have declared that no competing interests exist.

Objective: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice., Materials and Methods: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals., Conclusion: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil., (© 2022. The Author(s).)

Objective: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence., Materials and Methods: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans., Conclusion: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation., (© 2022. The Author(s).)

Background: The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of pemafibrate in clinical settings, a pilot study evaluating the association between drug use and detected events was performed in Japan., Aims: In this study, the association between detected events and the use of pemafibrate, utilizing pharmacy records maintained by community pharmacists, was investigated. We identified the newuser cohort using a test and active comparison drug and collected the baseline information. An active comparison group comprising new users was used to assess the events., Methods: A retrospective cohort study using questionnaires regarding baseline and event data was conducted by community pharmacists belonging to the Japan Pharmaceutical Association. The incidence of event and estimated hazard ratio were calculated using the Cox proportional hazards model that was adjusted for confounding factors, such as age and sex., Results: A total of 1294 patients using pemafibrate and 508 patients using fenofibrate were identified as new drug users. The most reported events involving suspected adverse reactions and add-on drugs were increased blood pressure and lipid-lowering effects with pemafibrate use, and nasopharyngitis, pruritus, dizziness, and lipid-lowering effects with fenofibrate use. No significant differences were found in commonly occurring events, except that an add-on anti-hypertensive drug has been used by pemafibrate users compared to fenofibrate users., Conclusion: This study conducted by pharmacists can facilitate the safety assessment of newly marketed drugs, as few drug use investigations with a comparator are carried out by the Japanese authority for pharmaceutical companies. However, further research is required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: We aimed to discuss and compare reported adverse reactions and drug add-ons associated with elobixibat and lubiprostone use in chronic constipation treatment, as the safety of these drugs has not been well examined in post-marketing clinical settings., Research Design and Methods: In this retrospective cohort study, using records of community pharmacies in Japan, we identified new users of elobixibat and lubiprostone. The Japan Pharmaceutical Association sent questionnaires regarding baseline and event data to community pharmacists. The incidence of events and hazard ratio (HR) associated with the study drugs were evaluated., Results: New users of elobixibat (n = 979) and lubiprostone (n = 829) were identified (mean age: 74 and 77 years; females: 59% and 53%, respectively). Although the crude risk ratio of adverse events for elobixibat was 0.79 (95% confidence interval: 0.63-0.99), there was no significant difference in the HR for any of the common events, including drug add-ons (n ≥ 5), compared with those for lubiprostone., Conclusion: No new safety concerns have been raised in relation to elobixibat and lubiprostone use for treating chronic constipation, although the HR of different events varied. Further larger-scale study is needed as the estimates for events of small numbers were unstable.

Delivering therapeutic nucleic acids to targeted cells and organs has been a challenge for decades. A novel technology to deliver oligonucleotide therapeutics to immune cells is here described. In this approach, a macromolecular complex of oligonucleotides and the β-1,3-glucan schizophyllan (SPG) is selectively delivered to cells expressing a lectin receptor, Dectin-1, via SPG-Dectin-1 interaction. Detailed investigation of Dectin-1-expressing cells revealed that Dectin-1 is expressed in all subsets of monocytes as well as dendritic cell (DC) populations, including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), in humans. The expression patterns in mice and humans are comparable, except for the expression in pDCs. The results indicate that Dectin-1 is expressed on cells capable of professional antigen presentation, except for B cells. We chose CD40 as a target gene for small interfering RNA (siRNA) as CD40 expression in antigen-presenting cells (APCs), particularly in DCs, plays critical roles in regulating immune responses. Dose-dependent cellular uptake of siCD40-SPG complexes was confirmed in cells expressing Dectin-1. Gene silencing activity was confirmed in vitro by the reduction of CD40 mRNA and by the site-specific cleavage of CD40 mRNA as determined by the 5' RNA ligase-mediated rapid amplification of cDNA ends (5'RLM-RACE) technique. In vivo activity of siCD40-SPG complexes was demonstrated as the reduced CD40 protein expression in monocytes and DCs in mice. Furthermore, the in vivo activity of siCD40-SPG targeting human CD40 was confirmed in cynomolgus monkeys by the 5'RLM-RACE technique. In conclusion, we have demonstrated the receptor-ligand binding-mediated delivery of siRNA targeting immune-regulating monocytes and DCs via the interaction of SPG and its receptor, Dectin-1. As monocytes and DCs play central roles in inducing and controlling immune responses, Dectin-1-targeted delivery of nucleic acids should provide a useful tool for developing drugs to treat a wide range of diseases, including autoimmune diseases, allergy, and cancer, as well as transplantation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To compare provocative test-based and long-term intraocular pressure variation parameters in patients with stable open-angle glaucoma., Methods: A prospective observational study was carried out in which stable open-angle glaucoma patients (⩾3 years of follow-up without any changes on current medical regimen) were consecutively enrolled. All patients were submitted to a water-drinking test. Long-term intraocular pressure parameters were obtained from isolated intraocular pressure measurements from each visit (⩾5 visits). We investigated the correlation and agreement between the following water-drinking test and long-term intraocular pressure parameters: mean, peak, and fluctuation. In addition, the percentage of eyes with significant intraocular pressure peaks during the water-drinking test (defined as a difference ⩾25% between water-drinking test intraocular pressure peak and mean long-term intraocular pressure) was assessed., Results: Sixty-three eyes from 63 open-angle glaucoma patients (mean age, 60.7 ± 11.8 years) were included. Mean and water-drinking test intraocular pressure peak correlated significantly with mean ( r  = 0.67) and maximum long-term intraocular pressure ( r  = 0.52), respectively ( p  < 0.01). The correlation between water-drinking test intraocular pressure fluctuation and long-term intraocular pressure fluctuation was not significant ( p  = 0.45). Limits of agreement from Bland-Altman plots exceeded the maximum allowed difference between methods (3 mm Hg) for all the intraocular pressure parameters analyzed, suggesting poor agreement between water-drinking test-derived and long-term intraocular pressure values. Overall, significant water-drinking test intraocular pressure peaks were observed in 39.7% of these eyes with stable open-angle glaucoma., Conclusion: Although some water-drinking test-based and long-term intraocular pressure parameters correlate significantly, water-drinking test results may not reflect the long-term intraocular pressure profile of stable open-angle glaucoma patients, as their agreement is poor. Many of these patients may experience significant water-drinking test intraocular pressure peaks, despite long-standing stable disease and unchanged medical regimen.

Purpose: To correlate provocative test-based intraocular pressure (IOP) variation parameters (fluctuation and peak) with functional status, and to compare these IOP parameters between treated eyes with asymmetric primary open-angle glaucoma (POAG)., Methods: A prospective observational study including consecutively treated patients with primary open-angle glaucoma was performed. Subjects with ocular diseases other than glaucoma or previous incisional glaucoma surgery were excluded. The primary inclusion criteria were 33 visual field tests and 32 years of follow-up, without any changes on current medical regimen. Long-term intraocular pressure parameters were acquired via isolated intraocular pressure measurements from the patients' last 5 office visits. To evaluate provocative test-based intraocular pressure parameters, all patients were submitted to a water drinking test. Initially, the partial correlation coefficients between each intraocular pressure variation parameter and visual field mean deviation were calculated, adjusting for the baseline intraocular pressure and number of antiglaucoma medications. In addition, each intraocular pressure parameter was compared between eyes with better visual field mean deviation and fellow eyes with worse visual field mean deviation in patients with asymmetric visual field loss (defined as an inter-eye visual field mean deviation difference of at least 3 dB)., Results: A total of 87 eyes (87 patients; mean age, 61.9 ± 12.5 years; 59.8% women) with primary open-angle glaucoma were included. The patients underwent a median of 5 visual field tests, with a mean follow-up of 4.3 ± 1.4 years. Neither long-term nor water-drinking test intraocular pressure variation parameters were significantly associated with visual field mean deviation values (p30.117). In the subgroup with asymmetric visual field loss (64 eyes of 32 patients; mean age, 65.0 ± 11.4 years), neither long-term water-drinking test intraocular pressure variation parameters differed significantly between eyes with better and worse visual field mean deviation (p30.400)., Conclusion: Our results indicate that neither long-term intraocular pressure variation parameters nor stress test-derived intraocular pressure metrics, as assessed by the water-drinking test, appear to correlate with the visual field status or differ significantly between eyes with asymmetric visual field damage, suggesting that other factors may explain such functional asymmetry, and that the water-drinking test does not add significant information to these cases.

Aim: To perform a correlation analysis between long-term intraocular pressure (IOP) variation parameters (mean, peak, and fluctuation) in patients with stable open-angle glaucoma (OAG)., Materials and Methods: A cross-sectional observational study was carried out, in which patients with stable OAG were consecutively enrolled. All patients had to have glaucomatous optic neuropathy and characteristic visual field (VF) defects. Key inclusion criteria were ≥5 VF tests, ≥3 disc photographs, and ≥3 years of follow-up without any changes in current medical regimen. Stable OAG was defined as nonprogressive VF results and absence of anatomical changes for at least 3 years. Long-term IOP variation parameters were obtained from isolated IOP measurements from each visit (minimum of five IOP measurements). The main outcome measure was the correlation between these IOP variation parameters., Results: Of the 63 patients studied, 37 (59%) were women, and the mean age was 61 ± 12 years. Among all the analyses, IOP mean and peak had the strongest correlation ( r = 0.94; 95% CI = 0.92-0.97; p < 0.001). There were also significant correlations between IOP peak and IOP fluctuation ( r = 0.84; 95% CI = 0.75-0.90; p < 0.001), and mean IOP and IOP fluctuation ( r = 0.62; 95% CI = 0.43-0.75; p < 0.001)., Conclusion: Most long-term IOP variation parameters evaluated seem to be highly correlated. Notably, the correlation between mean IOP and IOP peak was the strongest one. We believe this fact should be taken into consideration as their inclusion as individual variables in a multiple regression model could lead to misinterpretation of the data., Clinical Significance: Different well-designed studies are conflicting regarding which long-term IOP variation parameter is more clinically relevant. Our findings suggest that collinearity issues could explain in part the discrepant results among these studies evaluating the relationship between long-term IOP variation parameters and glaucoma prognosis., How to Cite This Article: Scoralick ALB, Gracitelli CPB, et al. Peak, Fluctuation, or Mean? A Correlation Analysis of Long-term Intraocular Pressure Variation Parameters in Patients with Stable Glaucoma. J Curr Glaucoma Pract 2019;13(1):28-31., Competing Interests: Source of support: Nil Conflict of interest: None

Purpose: Glaucomatous eyes with disc hemorrhage (DH) have a greater risk of paracentral visual field (VF) loss. However, not every DH eye presents with parafoveal scotoma (PFS), and contributing factors are still to be determined. In the present study, we investigated clinical and ocular factors associated with the presence of PFS in glaucomatous eyes with DH., Methods: A case-control study was carried out. One hundred thirty glaucomatous patients with DH were enrolled. They were divided into two groups based on two reliable 24-2 VF tests: those with PFS (defined as ≥3 adjacent points with p < 5% within the central 10 degrees of fixation, ≥1 point with p < 1% lying at the innermost paracentral points, in the same hemifield) and those without PFS. Clinical and ocular data from the time of DH detection were compared between groups. Factors associated with the presence of PFS were investigated through logistic regression., Results: The PFS group had a higher prevalence of Caucasian patients (82 vs. 47%; p < 0.01). Eyes with PFS had a more negative spherical equivalent and worse VF mean deviation (MD) index (p ≤ 0.01). There was a marginally significant intraocular pressure (IOP) difference between eyes with (15 mmHg) and without PFS (18 mmHg) at the time of DH detection (p = 0.10). Univariable analysis revealed PFS to be significantly associated with Caucasian race (OR, 3.02; p = 0.004), myopia (<-3 diopters; OR, 3.44; p = 0.039), and lower IOP (≤16 mmHg; OR, 2.10; p ≤ 0.047). Multivariable analysis, controlling for VF MD, revealed that only Caucasian race and myopia (as a continuous or categorical variable) remained significant in this model (p ≤ 0.038)., Conclusions: Caucasian race and the presence and magnitude of myopia were found to be significantly associated with the presence of PFS in glaucomatous eyes with DH. Our results may help clinicians in the identification and surveillance of these eyes at higher risk of central VF loss.

Purpose: To evaluate the incidence of intraocular pressure (IOP) spikes within the first postoperative hours following trabeculectomy (TRAB) and to determine possible associated factors., Methods: An observational study was carried out. We enrolled consecutive patients undergoing standard TRAB with mitomycin C. They were examined twice within the first few postoperative hours (hours 1-2 and 4-6) and 3 times after TRAB (on days 1, 7, and 30). Demographic and ocular data were collected. Main outcome measurements were postoperative IOP values at each time point and the frequency of IOP spikes, defined as IOP ≥25 mm Hg., Results: A total of 40 eyes of 40 patients were included (mean age 59.62 ± 13.37 years). Although IOP was significantly reduced to 11.14 ± 7.99 mm Hg at hours 1-2 (p < 0.01) and to 11.52 ± 7.30 mm Hg at hours 4-6 (p < 0.01), IOP spikes were documented in 3 patients (7.5%). In the group of patients with IOP spikes, we noted that there was a high incidence of black patients and that the surgeries had been performed by fellow surgeons., Conclusion: Although the majority of the cases (92.5% of the patients) did not present IOP spikes, 7.5% of our patients presented the event. In selected cases, such as those with advanced disease, fixation threat, and of black race, IOP should be monitored during the first few postoperative hours for the identification and adequate management of potential IOP spikes, preventing undesirable outcomes., (© 2017 S. Karger AG, Basel.)

Considering ethnic and anthropometric differences, it is important to obtain specific normative data on body composition (BC) for each population. The objectives of this study were to obtain the normative curve for the BC of Brazilian men and to compare them to the North American male population. A total of 403 healthy Brazilian men 20 years and older were included in the study. Data on concomitant diseases and physical activity were investigated using a structured questionnaire. Conditions that could affect lean and fat mass were excluded. BC was assessed via whole-body dual-energy X-ray absorptiometry (DXA) using a GE-Lunar device. Significance level was set as p < 0.05. Mean age and body mass index (BMI) were 46.0 ± 17.9 years and 26.2 ± 3.14 kg/m 2 , respectively. Mean skeletal mass index (SMI), appendicular lean mass by BMI (ALM BMI ), and fat mass index (FMI) were 8.38 ± 0.85, 0.949 ± 0.138, and 6.87 ± 2.43 kg/m 2 , respectively. There were negative associations among SMI (p < 0.001), ALM BMI (p < 0.001), and FMI (p = 0.002) with age. Comparison with the National Health and Nutrition Examination Survey (NHANES) III data, originally performed with a Hologic device, showed that Brazilian men had lower FMI and BF. This difference was minimized after converting the NHANES results to the GE-Lunar database. Brazilian men had lower SMI than American men measured in NHANES III. FMI was less influenced by ethnicity than by BMI, and it could be used as a standard measure for assessing fat excess or adiposity. Our data suggest that conversion to each specific manufacturer's database should be performed to minimize differences in body composition between populations.

Aim: To investigate surgical outcomes and success predictors of transconjunctival scleral flap resuturing for the management of hypotony due to overfiltration following trabeculectomy with mitomycin C., Materials and Methods: Noncomparative, retrospective, interventional case series in which all glaucoma patients from two glaucoma services undergoing transconjunctival scleral flap resuturing between May 2012 and July 2016 were enrolled. Included eyes had to have hypotony [intraocular pressure (IOP) < 6 mm Hg] and/or hypotony maculopathy caused by excessive filtration following trabeculectomy. Key exclusion criteria were wound/bleb leaking and postoperative ocular trauma or infection. Preoperative and postoperative IOP, best-corrected visual acuity (BCVA), fundus imaging, surgical complications, and any subsequent related events or procedures were recorded. Rates of postsurgical hypotony and/or maculopathy resolution and possible success predictors were investigated., Results: A total of 22 patients (22 eyes) with a mean age of 56.4 ± 15.2 years were included. Median follow-up was 245 days [interquartilerange (IR); 120-817 days] and mean IOP was increased from 2.9 ± 1.5 mm Hg (1-6 mm Hg) to 8.5 ± 3.1 mm Hg (2-16 mm Hg) at the last follow-up visit (p < 0.01). Approximately 75% of the cases (16 out of 22) had an IOP between 7 and 18 mm Hg at the end of the follow-up period. Median BCVA (log MAR) at last follow-up visit [0.1 (IR; 0.0- 0.3)] was significantly better than preoperative BCVA [0.4 (IR; 0.11.0); p < 0.01]. Hypotony resolved in 81% of the cases, while maculopathy resolution was found in 85% of the cases. Time interval between trabeculectomy and flap resuturing was the only factor significantly associated with patient's IOP at last follow-up visit (R 2 = 0.23; p = 0.036). Success rates (IOP > 6 mm Hg at last follow-up visit) were halved in those left untreated for more than 6 months. No serious adverse event was recorded., Conclusion: Our findings support the use of transconjunctival scleral flap resuturing as an effective and safe alternative for hypotony management due to overflitration following trabeculectomy. As time interval seems to influence the odds of hypotony resolution, early intervention is recommended., How to Cite This Article: Scoralick ALB, Almeida I, Ushida M, Dias DT, Dorairaj S, Prata TS, Kanadani FN, Hypotony Management through Transconjunctival Scleral Flap Resuturing: Analysis of Surgical Outcomes and Success Predictors. J Curr Glaucoma Pract 2017;11(2):58-62., Competing Interests: Source of support: Nil Conflict of interest: None

Background: To analyze the most common neurophthalmological conditions that may mimic glaucomatous optic neuropathy and to determine which most often lead to misdiagnosis when evaluated by a glaucoma specialist., Methods: We reviewed the charts of consecutive patients with optic neuropathies caused by neurophthalmological conditions screened in a single Eye Clinic within a period of 24 months. Within these enrolled patients, we selected the eyes whose fundoscopic appearance could resemble glaucoma based in pre-defined criteria (vertical cup-to-disc ratio ≥0.6, asymmetry of the cup-to-disc ratio ≥0.2 between eyes, presence of localized retinal nerve fiber layer and/or neuroretinal rim defects, and disc haemorrhages). Then, color fundus photographs and Humphrey Visual Field tests (HVF) of these eyes were mixed with tests from 21 consecutive glaucomatous patients (42 eyes with normal tension glaucoma). These images were mixed randomly and a masked glaucoma specialist was asked to distinguish if each set of exams was from a patient with glaucoma or with a neurophthalmologic condition., Results: Among the 101 eyes (68 patients) enrolled with neurophthalmological diseases, 16 (15.8%) were classified as conditions that could mimic glaucoma. The most common diagnoses were ischemic optic neuropathy (25%), compressive optic neuropathy (18.7%) and hereditary optic neuropathy (18.7%). Based on the analysis of fundus photographs and HVF tests, 25% of these were misdiagnosed as glaucoma (two ischemic optic neuropathies and two congenital optic disc anomalies). Conversely, 11.9% of the glaucomatous neuropathies were misdiagnosed as neurophthalmological disorders. Overall, the glaucoma specialist correctly diagnosed 84.5% of the eyes., Conclusions: Some neurophthalmological disorders can mimic glaucoma. In our study, isquemic and compressive optic neuropathies were the ones that most often did so. Almost one quarter of the eyes were misdiagnosed when evaluated by a glaucoma specialist, which can lead to inadequate management and influence the prognosis of these patients.

Background: To identify success predictors and to study the role of the fellow untreated eye as a co-variable for adjustment of intraocular pressure (IOP) outcomes following selective laser trabeculoplasty (SLT) in early open-angle glaucoma (OAG) patients., Methods: A case series was carried out. Patients with uncontrolled early OAG or ocular hypertension (inadequate IOP control requiring additional treatment) underwent SLT (one single laser session) performed by the same surgeon in a standardized fashion. The same preoperative medical regimen was maintained during follow-up for all patients. Post-treatment assessments were scheduled at week 1 and months 1, 2, and 3. In order to account for possible influence of IOP fluctuation on laser outcomes, post-laser IOP values of the treated eye of each patient were also analyzed adjusting for IOP changes (between visits variation) of the untreated fellow eye (adjusted analysis). Pre and post-laser IOP values were compared using paired t-test. Factors associated with the magnitude of IOP reduction were investigated using multiple regression analysis., Results: A total of 45 eyes of 45 patients were enrolled. Mean IOP was reduced from 20.8 ± 5.1 to 14.9 ± 2.9 mmHg at month 3 (p < 0.001). Adjusted success rate (defined as IOP reduction ≥ 20%) was 64% and mean percentage of IOP reduction was 23.1 ± 14.3% at last follow-up visit. Considering unadjusted post-laser IOP values, it was found a 20% greater absolute IOP reduction (median [interquartile range] 6 mmHg [4-7] vs 5 mmHg [3-7]; p = 0.04), with a success rate of 76%. Although baseline IOP was significantly associated with both adjusted and unadjusted post-laser IOP reduction, a stronger association was found when unadjusted IOP values were considered (p < 0.001 and R 2  = 0.35; p < 0.001 and R 2  = 0.67, respectively). Age, mean deviation (MD) index, central corneal thickness and type of glaucoma were not significant predictors (p ≥ 0.150)., Conclusions: In this group of patients with early OAG or ocular hypertension, our short-term results confirmed SLT as a safe and effective alternative for IOP reduction. Although better outcomes were found in eyes with higher preoperative IOP, this effect was mitigated when results were adjusted to the fellow untreated eye (to the influence of between visits-IOP fluctuations).

Although eye drops are frequently used as an initial treatment option for open angle glaucoma (OAG), side effects, and poor adherence, among others, may compromise treatment efficacy. In this scenario, laser trabeculoplasty is an interesting therapeutic option for open angle glaucoma cases. Commonly used for many years as a last alternative prior to glaucoma incisional surgery, laser trabeculoplasty has been changing its indication after the advent of selective laser trabeculoplasty (SLT). In the current review, we critically evaluated the published data regarding the use of laser trabeculoplasty as a first treatment option for open angle glaucoma patients. Studies using SLT as a first-line treatment have encouraging findings. One-year efficacy results are comparable to those obtained with prostaglandin analogues, with a good safety profile. Although the laser´s effect is known to be transitory, recent data suggest it can be successfully repeated in cases with good response to the first SLT treatment.

Among all glaucoma suspects, eyes with optic nerve head features suspicious or suggestive of early glaucoma are probably those that offer the greatest challenge for clinicians. In contrast with the robust longitudinal data published on ocular hypertension, there is no specific management guideline for these patients. Therefore, evaluating eyes with suspicious optic disc appearance and normal intraocular pressure (IOP), we sought to investigate potential differences in clinical and epidemiological characteristics to differentiate those with normal-tension glaucoma (NTG) from those with presumed large physiological optic disc cups (pLPC). In this observational case-control study, we consecutively enrolled individuals with pLPC and NTG. All eyes had vertical cup-to-disc ratio (VCDR)≥0.6 and untreated IOP<21 mmHg. Glaucomatous eyes had reproducible visual field defects. Eyes with pLPC required normal visual fields and ≥30 months of follow-up with no evidence of glaucomatous neuropathy. Clinical and epidemiological parameters were compared between groups. Eighty-four individuals with pLPC and 40 NTG patients were included. Regarding our main results, NTG patients were significantly older and with a higher prevalence of Japanese descendants (p<0.01). Not only did pLPC eyes have smaller mean VCDR, but also larger optic discs (p≤0.04). There were no significant differences for gender, central corneal thickness, and spherical equivalent (p≥0.38). Significant odds ratios (OR) were found for race (OR = 2.42; for Japanese ancestry), age (OR = 1.05), VCDR (OR = 5.03), and disc size (OR = 0.04; p≤0.04). In conclusion, in patients with suspicious optic disc and normal IOP, those with older age, Japanese ancestry, smaller optic discs, and larger VCDR are more likely to have NTG, and therefore, deserve deeper investigation and closer monitoring.

Conventional dendritic cells (cDCs) present α-galactosylceramide (αGC) to invariant natural killer T (iNKT) cells through CD1d. Among cDC subsets, CD8(+) DCs efficiently induce IFN-γ production in iNKT cells. Using fluorescence-labeled αGC, we showed that CD8(+) DCs incorporated larger amounts of αGC and kept it intact longer than CD8(-) DCs. Histological analyses revealed that Langerin(+)CD8(+) DCs in the splenic marginal zone, which was the unique equipment to capture blood-borne antigens, preferably incorporated αGC, and the depletion of Langerin(+) cells decreased IFN-γ and IL-12 production in response to αGC. Furthermore, splenic Langerin(+)CD8(+) DCs expressed more membrane-bound CXCL16, which possibly anchored iNKT cells in the marginal zone, than CD8(-) DCs. Collectively, it is suggested that the cellular properties and localization of CD8(+) DCs are important for stimulation of iNKT cells by αGC., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Propolis, a resinous substance that honeybees collect to protect their beehive from enemies, is reported to have various biological activities. In our screening program to search for antiangiogenic compounds from propolis, the ethanol extracts of Okinawan propolis (EEOP) showed significant antiangiogenic activities in a tube formation assay with human umbilical vein endothelial cells (HUVECs) in vitro at 3.13  μ g/mL and chorioallantoic membrane (CAM) assay in vivo at 25  μ g/egg. To elucidate the active compounds of EEOP and their mode of action, we isolated some prenylated flavonoids from EEOP and found that nymphaeol-A had the strongest antiangiogenic activity among them. Nymphaeol-A significantly reduced in vivo neovessel formation in the CAM assay at 25  μ g/egg. At the molecular level, nymphaeol-A markedly inactivated mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2), whose molecular activations signal new vessel formation in HUVECs. In addition, nymphaeol-A dose- and time-dependently induced caspase-dependent apoptosis in tube-forming HUVECs. Taken together, nymphaeol-A was shown to inhibit angiogenesis at least in part via inactivation of MEK1/2-ERK1/2 signaling and induction of caspase-dependent apoptosis. Okinawan propolis and its major component, nymphaeol-A, may be useful agents for preventing tumor-induced angiogenesis.

Sulfatide-reactive type II NKT cells, the so-called non-invariant NKT (non-iNKT) cells, have been shown to counteract invariant NKT (iNKT) cell activity. However, the effects of sulfatide on activation of iNKT cells by α-galactocylceramide (αGC) in the context of CD1d have not been studied in detail. Therefore, we studied the blocking effect of sulfatide on αGC-induced iNKT cell activation by dendritic cells (DCs). Even in the absence of non-iNKT cells, sulfatide inhibited αGC-mediated iNKT cell activation by reducing αGC/CD1d complex formations in a dose-dependent manner. This was also confirmed in a cell-free setting using immobilized CD1d-Ig. Moreover, simultaneous injection of αGC with sulfatide decreased αGC/CD1d complex formations on DCs, accompanied by the reduced CD40L-up-regulation and IFN-γ production by iNKT cells and IL-12p70 production by DCs. However, sulfatide by itself did not interfere with the presentation of MHC class II-mediated antigen presentation to specific T cells. These results demonstrate that sulfatide competes with αGC to be loaded onto CD1d along the endocytic pathway in DCs, thereby inhibiting the iNKT cell response.

Aspirin's inhibitory effect on platelet function has been shown to be highly heterogeneous. However, due to the considerable individual variation in pharmacokinetics after aspirin intake, it has been difficult to investigate the mechanism of aspirin resistance empirically. Our objective was to examine whether platelet responsiveness to in vitro aspirin treatment could be affected by cyclooxygenase (COX)-1/2 protein levels in platelets or single-nucleotide polymorphisms (SNPs), which could possibly change specific activity of enzymes and/or aspirin susceptibility. Collagen/epinephrine closure time (CEPI-CT) of PFA-100 in blood from 178 healthy males was assessed with/without aspirin. Platelet COX-1 protein levels and the sequences of COX-1 gene exons were examined in three groups categorized by CEPI-CT: PR (Poor responders to aspirin), 10 people showing the shortest CEPI-CT under aspirin; GR-High or GR-Low (good responders to aspirin with high or low platelet basal reactivity), 10 people showing CEPI-CT over 300 s under aspirin and having the shortest or longest basal CEPI-CT, respectively. We analyzed the three groups, representing phenotypic extremes, aiming to increase statistical power to investigate the possible relevance of COXs to platelet response to aspirin. Western blot analysis revealed that COX-1 was abundantly expressed in platelets at comparable levels among the three groups, whereas COX-2 was undetectable. The frequencies of nonsynonymous COX-1/2 SNPs were unlikely to explain the difference in aspirin responsiveness considering the observed genotype frequencies and wide individual variation in platelet response. These results suggest that heterogeneity in platelet responsiveness to in vitro aspirin is independent of COX-1/2 protein levels and SNPs.

Introduction: Aspirin is one of the most effective antiplatelet agents and is now commonly used to prevent vascular events. In some patients, however, recurrent vascular events have been demonstrated despite aspirin therapy. Our objective was to characterize individuals showing poor response to in vitro effect of aspirin, using PFA-100., Methods: One hundred sixty-eight healthy male subjects were analyzed. We assessed platelet function tests, including PFA-100, whole blood aggregation, and optical platelet aggregation. Also measured were hemostatic and other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250 s with PFA-100 when incubated with 10 microM aspirin, whereas good responders were defined as having a CEPI-CT of more than 250 s., Results and Conclusions: PFA-100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%) were good responders (GR). Poor responsiveness was significantly associated with (1) higher basal platelet activities in PFA-100, as well as in whole blood aggregation and aggregometer;(2) increased level of adiponectin (8.8+/-4.1 micro g/mL [PR] vs 7.3+/-2.9 micro g/mL [GR], p=0.010);and (3) the presence of diabetes mellitus (17.5% [PR] vs 4.7% [GR], p=0.009). Importantly, whereas 24% of the subjects showed insufficient inhibition in PFA-100 when incubated with 10 microM aspirin, almost all subjects showed maximum inhibition with 30 microM aspirin. These observations suggest that higher doses of aspirin might overcome aspirin resistance.

We experienced a case of congenital rubella syndrome (CRS) due to infection after maternal antibody conversion with vaccine. The mother was immunized with rubella vaccine at 14 years of age, and was confirmed as having rubella-specific hemagglutination inhibition (HI) antibody at the 1:16 level both at ages 26 and 30 during preceding pregnancies. At the second week of the third gestation, her second child developed rubella. She did not suffer any symptoms, but was found to have rubella HI antibody at the 1:512 level at 9 weeks of gestation. She delivered a male baby weighing 2,545 g at 38 weeks of gestation. He had congenital pneumonia, patent ductus arteriosus, bilateral cataracts, sensorineural deafness, and periventricular calcification of the brain. The rubella-specific antibody was 1:512 by HI and 10.1 by IgM enzyme-linked immunosorbent assay. According to these observations, he was diagnosed as having CRS. The rubella virus genome was detected in the fluids of the vitreous body using RT-nested PCR. This case emphasizes the importance of double-dose immunization (once in infants and once in young adults) in order to obtain an adequate level of antibody with duration sufficient to ensure the prevention of CRS.

Objective: The purpose of this study was to evaluate the subjective quality of Joint Photographic Experts Group (JPEG) compressed images of intraoral radiographs with file sizes of 30 kilobytes or less, which can be transmitted quickly on the World Wide Web., Study Design: Conventional intraoral radiographs were digitized at sampling rates of 100, 200, 300, 400, and 600 dots per inch through use of a flatbed scanner and saved in JPEG format in 11 compression degrees. Fifty-five combinations of sampling rate and compression degree were evaluated by means of a visual analog scale. Sampling rate and compression degree combinations whose quality was inferior to that of an average image were excluded. The quality of the remaining combinations was subsequently evaluated through assessment of 8 anatomical features in each image., Results: Forty of the 55 combinations provided a file size less than 30 kilobytes. Thirty combinations obtained VAS scores of 0 or higher on the standardized VAS. As a result, 16 combinations of sampling and compression conditions were selected for the second part of the study. Only one combination of sampling rate and compression degree was found to provide sufficient image quality for all 8 anatomical features., Conclusions: Under the file size limit of the study design, the full-sized compressed image of an intraoral radiograph did not always provide sufficient quality. This problem will be reduced by improvements in telecommunications infrastructure, which will permit faster transfer of files of larger size.

We report the first case of the syndrome of periodic adrenocorticotropin (ACTH) and vasopressin (ADH) discharge associated with focal glomerulosclerosis. Approximately 30 cases of this syndrome have so far been reported in Japan, but no cases associated with renal dysfunction have yet been reported. The patient, a 10-year-old Japanese boy, was referred to our hospital because of recurrent attacks of vomiting. He was diagnosed as having this syndrome from clinical and laboratory findings. While various drugs were tried to manage his vomiting attacks, only valproic acid appeared to be effective in reducing the frequency of the attacks. Chronic nephritis was manifested when the patient was 12 years old, which required treatment with continuous ambulatory peritoneal dialysis. Valproic acid was proved to be effective in reducing the number of attacks over 4 months.

We report here a case of vertebral artery dissection, which is rare in childhood. A 12-year-old, previous healthy girl was admitted to our hospital with symptoms of vertigo, tinnitus, hearing loss, nausea and vomiting. Although there was neither higher cortical dysfunction, motor weakness, sensory disturbance nor slurred speech. She could not stand up because of severe vertigo. Cranial magnetic resonance imaging (MRI) revealed a subacute cerebellar infarct. A left vertebral artery angiogram on the hospital day 3 demonstrated a sharp narrowing at the C1-C2 level. After an anticoagulant therapy for about 2 weeks, all the symptoms disappeared except for mild tinnitus. Two months later, a left vertebral artery angiogram showed an abrupt occlusion at the C1 level. MRI T1-weighted images demonstrated a thrombus within the false lumen of the dissected vessels. A flow void revealed the patency of the residual true lumen. From these findings, we made a diagnosis of vertebral artery dissection, which was considered to have caused cerebellar infarction. The patient was mostly normal at discharge, and 100 mg/day of aspirin has been given until present.

We report a 6-year-old girl with Japanese B encephalitis. The initial symptoms were high fever, headache and vomiting. On the second day of illness, she developed hemiconvulsion and was admitted to our hospital. Physical examination demonstrated a stiff neck. C-reactive protein elevated to 22.7 mg/dl. CSF examination showed a marked increase in the cell count (10,896/3 mm3). During the course of the treatment, she showed transient hemiparesis and dysphagia, followed by akinetic mutism lasting for about a month. The patient was left with severe cognitive and memory impairment and complex partial seizures but no motor dysfunction. Japanese B encephalitis was diagnosed by means of serological examination. Magnetic resonance imaging revealed cystic lesions in the medial and posterior thalamus and substantia nigra and severe atrophy of the hippocampus. Despite the involvement of substantia nigra, the patient had no parkinsonism. The cognitive impairment may in part be explained by the lesions in the medical and posterior thalamus.

Objective: The aim of this study was to compare several values for consistency obtained by charged-coupled-device-based direct digital intraoral radiography with those obtained by conventional film-based radiography to evaluate observer agreement in determining the depth of proximal caries., Study Design: A total of 93 proximal surfaces on radiologic images that were obtained by both the conventional film-based bite-wing technique and by direct digital intraoral radiography were evaluated by six observers. One of these observers also evaluated the same images six months after the initial evaluation. The kappa value, consistency ratio, agreement ratio, and Kendall's correlation coefficient were calculated for interobserver and intraobserver agreement., Results: The overall kappa values for interobserver agreement were 0.439 and 0.424 in the direct digital system and the film-based radiography, respectively. The depth-related change of the values showed similar patterns in the two modalities for both interobserver and intraobserver agreement., Conclusion: The digital intraoral system resulted in no deterioration in observer agreement, and it presents no problems for clinical use with respect to the reliability of diagnosis.