Clinical features of patients with mutations in genes for nanophthalmos.

BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (PRSS56), membrane-type frizzled-related protein (MFRP), myelin regulatory factor (MYRF) and transmembrane protein 98 (TMEM98) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. METHODS: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. RESULTS: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP. Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. CONCLUSION: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.

mm9_circ_014683 regulates microglia polarization through canonical NFκB signaling pathway in diabetic retinopathy.

Diabetic retinopathy (DR) is still the major cause of visual loss in working-aged people, one of the critical pathological processes are retinal microglia-mediated inflammation. Our previous study demonstrated that enhanced M1 microglial polarization was involved in retinal inflammation in DR, but the detailed mechanism needs further investigation. Circular RNAs (circRNAs) are important kind of noncoding RNAs involved in the regulation of various cell biological processes. Herein, the circRNA expression profiles of BV2 mouse microglia treated with or without glucose were detected, and a total of 347 differentially expressed circRNAs were identified in glucose-treated BV2 cells. The key circRNA mm9_circ_014683 increased after glucose stimulation. Inhibiting or overexpressing mm9_circ_014683 showed no effect on the proliferation and apoptosis of microglia. Inhibiting mm9_circ_014683 impeded M1 polarization and promoted M2 polarization, and overexpressing mm9_circ_014683 showed the opposite effect. A total of 216 differentially expressed genes were identified in mm9_circ_014683-knockdown BV2 cells, which were enriched in several signaling pathways, including the NFκB signaling pathway. Moreover, mm9_circ_014683 positively regulated the canonical, NFκB signaling pathway. Besides, mm9_circ_014683 was highly expressed in the retinal microglia of diabetic mice, and intraocular injection of Lv-circRNA inhibited M1 but enhanced M2 retinal microglial polarization. In conclusion, mm9_circ_014683 regulates microglial polarization through the canonical NFκB signaling pathway in diabetic retinopathy. This study may provide insight into the pathogenesis and treatment of DR.

Quantitative assessment of extraocular muscles in Graves' ophthalmopathy using T1 mapping.

OBJECTIVE: To evaluate the performance of T1 mapping in the characterization of extraocular muscles (EOMs) of Graves' ophthalmopathy (GO) patients and investigate its feasibility in assessing the response to glucocorticoid therapy in active GO patients. METHODS: A total of 133 participants (78 active GO, 23 inactive GO, 18 Graves' disease (GD) patients, and 14 healthy volunteers) were consecutively enrolled from July 2018 to December 2020. Native T1 (nT1) and postcontrast T1 (cT1) values of EOMs were measured and compared. The variations in T1 mapping metrics of EOMs were compared pre/post glucocorticoid treatment in 23 follow-up active GO patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The nT1 of EOMs in GO patients was higher than that in GD patients and healthy volunteers. The nT1 of superior rectus (SR) in active GO was higher than that in inactive GO patients, and it could be used as a potential marker of GO activity (OR: 1.003; 95% CI: 1.001, 1.004), with a diagnostic sensitivity of 86.3% and specificity of 43.7%. Meanwhile, the cT1 of SR, inferior rectus (IR), and medial rectus (MR) in inactive GO patients were higher than those in active GO patients. The nT1 of EOMs achieved sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active GO patients (AUC, 0.797; sensitivity, 71.9%; specificity, 85.7%). CONCLUSIONS: T1 mapping could quantitatively assess the activity of GO and the response to glucocorticoid therapy in active GO patients and may even potentially reflect the fibrosis of EOMs. CLINICAL RELEVANCE STATEMENT: T1 values can reflect the pathological status of the extraocular muscle. T1 mapping could help to quantitatively assess the clinical activity of GO and the response to glucocorticoid therapy in active GO patients. KEY POINTS: • Graves' ophthalmopathy patients had greater nT1 of extraocular muscles than Graves' disease patients and healthy volunteers, and nT1 of the superior rectus could be a potential marker of Graves' ophthalmopathy activity. • The cT1 of extraocular muscles in inactive Graves' ophthalmopathy patients was higher than that in active Graves' ophthalmopathy patients, and it might be associated with muscle fibrosis. • nT1 of extraocular muscles could offer sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active Graves' ophthalmopathy patients.

Comprehensive analysis of ferritinophagy-related genes and immune infiltration landscape in diabetic retinopathy.

Background: Diabetic retinopathy (DR) is deemed a microangiopathy and neurodegenerative disorder, which is a primary reason of visual impairment in the world. Ferritinophagy is a critical regulator of ferroptosis and has a vital part in the etiopathogenesis of DR. Nevertheless, its molecular mechanism in DR remains to be expounded. Methods: The GSE146615 dataset was adopted to identify ferritinophagy-related differentially expressed genes (FRDEGs). The interactions and biological functions of the genes were described by means of functional enrichment analysis (FEA). The enriched gene sets were analyzed utilizing gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). Identification of hub genes was performed utilizing protein-protein interaction (PPI) analysis. mRNA-miRNA, mRNA-transcription factors (TF), mRNA-drugs, mRNA-RNA-binding proteins (RBP) interaction networks were constructed. In addition, datasets GSE60436 and GSE94019 were utilized for validation. The diagnostic performance of FRDEGs was assessed by means of receiver-operating characteristic curve monofactor analysis, followed by immune infiltration analysis. Lastly, quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to analyze the validation of genes. Results: In total, the identification of eight FRDEGs was completed utilizing differential expression analysis. FEA mainly implicated the autophagy of mitochondrion, mitochondrion disassembly, autophagosome assembly, and organization pathways. GSEA and GSVA mainly implicated the interferon alpha response, ultraviolet response up, interferon gamma response, apical junction, pical surface, and allograft rejection pathways. BECN1 and HERC2 displayed high diagnostic accuracies in validation sets. Immune infiltration analysis revealed that several immune cells related to ferritinophagy may be play potential roles in DR. Finally, qRT-PCR was utilized to validate the upregulated expression of BECN1 as well as the downregulated expression of BCAT2 and ATG7 in the DR model. Conclusion: BECN1, HERC2, ATG7, and BCAT2 act as potential biomarkers for DR and might regulate ferritinophagy and the immune microenvironment to influence its development and progression. This research can provide new insights into pathogenesis of DR related to ferritinophagy.

Microcatheter-Assisted Circumferential Trabeculotomy After Failed Glaucoma Surgeries in Childhood Glaucoma.

PURPOSE: To evaluate the outcomes of microcatheter-assisted trabeculotomy (MAT) in childhood glaucoma (primary congenital glaucoma [PCG], juvenile open-angle glaucoma [JOAG], and secondary childhood glaucoma [SCG]) after failed glaucoma surgery. DESIGN: Retrospective interventional case series. METHODS: Patients with childhood glaucoma who underwent MAT after failed glaucoma surgery with at least 12 months of follow-up were evaluated. Pre- and postoperative intraocular pressure (IOP) and the number of glaucoma medications were recorded and compared. Success was defined as an IOP ≤21 mm Hg with or without glaucoma medication. Analysis of variance was used to compare the glaucoma subgroups. RESULTS: Forty-five eyes (42 patients) with a median follow-up period of 19 months were included. The median age at the time of MAT was 10 (range, 0.8-33) years. The mean number of previous surgeries was 1.3 ± 0.5. The IOP had significantly reduced from baseline in all PCG, JOAG, and SCG patients (27.9 ± 4.5 vs 16.3 ± 8.0 mm Hg, P = .001; and 30.8 ± 9.4 vs 13.5 ± 3.0 mm Hg, P < .001; and 31.5 ± 7.1 vs 16.5 ± 5.3 mm Hg, P = .001, respectively). Fewer glaucoma medications were needed after MAT in all 3 groups (each P < .001). At the last visit, the total success rates in PCG, JOAG, and SCG were 93.8%, 100%, and 88.9%, respectively. No severe complications were observed. CONCLUSION: MAT can effectively manage PCG, JOAG, and SCG after failed surgeries, providing successful outcomes and no serious complications. Following failed glaucoma surgeries, MAT may offer these patients with childhood glaucoma an excellent opportunity to achieve IOP control.

Effect of Combined Surgery in Patients with Complex Nanophthalmos.

(1) Background: To evaluate the efficacy and safety of combined surgery (limited pars plana vitrectomy, anterior-chamber stabilized phacoemulsification, IOL implantation and posterior capsulotomy, LPPV + ACSP + IOL + PC) in complex nanophthalmos. (2) Methods: Patients with complex nanophthalmos were recruited to undergo LPPV + ACSP + IOL + PC from January 2017 to February 2021. Preoperative and post-operative intraocular pressure (IOP), best corrected visual acuity (BCVA), anterior chamber depth (ACD), and number of glaucoma medications were compared using the paired t-test or Wilcoxon signed rank sum tests. Surgical success rate was evaluated. Surgery-associated complications were documented. (3) Results: Forty-five eyes of 37 patients with complex nanophthalmos were enrolled. The mean follow-up period was 21.7 ± 10.6 months after surgery. Mean IOP decreased from 32.7 ± 8.7 mmHg before surgery to 16.9 ± 4.5 mmHg (p < 0.001) at the final follow-up visit, mean logMAR BCVA improved from 1.28 ± 0.64 to 0.96 ± 0.44 (p < 0.001), mean ACD significantly increased from 1.14 ± 0.51 mm to 3.07 ± 0.66 mm (p < 0.001), and the median number of glaucoma medications dropped from 3 (1, 4) to 2 (0, 4) (p < 0.001). The success rate was 88.9% (40 eyes) at the final follow-up visit. Two eyes had localized choroidal detachments which resolved with medical treatment. (4) Conclusions: LPPV + ACSP + IOL + PC is a safe and effective surgical procedure, which can decrease IOP, improve BCVA, deepen the anterior chamber, and reduce the number of glaucoma medications in patients with complex nanophthalmos. It can be considered as one of the first treatment in nanophthalmic eyes with complex conditions.

Long-Term Visual Outcomes of Primary Congenital Glaucoma in China.

INTRODUCTION: The aim of this study was to investigate the long-term visual outcomes and factors associated with vision loss in Chinese patients with primary congenital glaucoma (PCG) after successful intraocular pressure (IOP) control (IOP ≤21 mm Hg). METHODS: PCG patients with IOP control who were examined in the glaucoma clinic at Zhongshan Ophthalmic Center from 2019 to 2020 were enrolled. The final visual outcome was evaluated by the best corrected visual acuity (VA). Univariate and multivariate analyses were used to investigate the associations of visual impairment with potential risk factors. The causes for decreased VA (<20/50) were also analyzed. RESULTS: Fifty-nine patients (95 eyes) were included in the cohort, with a mean age of 8.7 years. The mean logMAR VA was 0.62 ± 0.64. The VAs of eyes treated for PCG were good (≥20/50) in 56%, fair (20/60-20/200) in 30%, and poor (<20/200) in 14%. The most common cause of decreased VA was amblyopia (64.3%). Multivariate logistic regression analysis showed that undergoing multiple surgeries (OR: 4.86, 95% CI: 1.11-21.16, p = 0.035) was significantly associated with visual impairment. CONCLUSION: The results showed that good VA was attainable in approximately half of PCG eyes under IOP control. Prompt and effective treatment of PCG, management of amblyopia and ocular comorbidities may be potential steps toward achieving good visual outcomes in PCG patients.

ALKBH5-Mediated m6A Modification of A20 Regulates Microglia Polarization in Diabetic Retinopathy.

Background: To investigate the role of microglia polarization in the pathogenesis of diabetic retinopathy, and study the mechanism of ALKBH5-mediated m6A modification of A20 of retinal microglia polarization. Methods: Diabetics rats were constructed and the M1/M2 polarization of retinal microglia was determined using immunofluorescence, flow cytometry, and quantitative real-time PCR (qRT-PCR). Glucose at different concentrations was added to treat the microglia, and the polarization rate was detected. RNA sequencing was performed to identify the differentially expressed gene in glucose treated microglia, and A20 expression was confirmed by qRT-PCR and western blotting. Lentiviruses encoding shRNA for A20 or overexpressing A20 were constructed to clarify the role of A20 in microglia polarization in vitro and vivo. N6-methyladenosine (m6A) modification level and degradation rate of A20 were determined and m6A related proteins were detected. Results: Diabetics rats showed a higher M1 polarization rate but lower M2 polarization rate of retinal microglia. With the increase of glucose concentration, microglia tend to polarize into M1 inflammatory type rather than M2 anti-inflammatory type. Shown by RNA sequencing, glucose treated microglia showed a differentially expressed gene profile, which was enriched in kinds of inflammatory categories and pathways. A20 expression was lower in microglia with glucose treatment, which was demonstrated to negatively regulate the M1 polarization. Moreover, intraocular injection of A20-overexpression lentiviruses (OE-A20) rectified the enhanced M1 retinal microglia polarization of diabetes rats. The higher m6A modification level and faster degradation rate of A20 was observed in glucose treated microglia, which was mediated by m6A demethylase ALKBH5. Conclusion: Lower expression A20 resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification. This study may provide new perspectives on not only the pathogenesis but also the diagnosis and treatment for diabetic retinopathy.

JUE Insight: Distributional Impacts of Retail Vaccine Availability.

We examine the potential for exploiting retailer location choice in targeting health interventions. Using geospatial data, we quantify proximity to vaccines created by a U.S. federal program distributing COVID-19 vaccines to commercial retail pharmacies. We assess the distributional impacts of a proposal to provide vaccines at Dollar General, a low-priced general merchandise retailer. Adding Dollar General to the federal program would substantially decrease the distance to vaccine sites for low-income, rural, and minority U.S. households, groups for which COVID-19 vaccine take-up has been disproportionately slow.

Clinical and Ultrasound Biomicroscopic Characteristics of Congenital Fibrovascular Pupillary Membrane-Induced Secondary Glaucoma.

Purpose: The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG). Design: Cross-sectional case series. Methods: Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA. Results: The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all P ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I ("U" shape), 34% type II ("Y" shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I (P = 0.045). Conclusion: Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.

Ocular Biometry of Primary Angle-Closure Disease in Younger Patients.

Background: The purpose of this study was to analyze the ocular biometric parameters of primary angle-closure disease (PACD) in younger patients and compare them with those of elderly patients. Methods: This clinic-based, cross-sectional study included 154 eyes of 154 patients with PACD, consisting of 77 eyes of patients aged 40 years or younger and 77 eyes of patients older than 40. The PACD case definition was compatible with the ISGEO definition. Anterior segment parameters were measured by ultrasound biomicroscopy, axial length (AL) and lens thickness (LT) were measured by A-scan ultrasonography measurements, and the thickness of the retina and choroid were measured by optical coherence tomography. The differences in ocular biometric parameters between different age groups were compared by independent sample t-tests or Mann-Whitney U tests, and the correlation between the parameters and age was analyzed. Results: Compared to older PACD patients, the lens vault(LV),LV/LT and subfoveal choroidal thickness (SFCT) of younger patients were larger, while the peripheral and mean iris thickness (IT), trabecular-ciliary angle (TCA), ciliary body thickness (CBT), AL and LT were smaller (all P < 0.01). There was no significant difference in anterior chamber depth, anterior chamber width, pupil diameter, angle opening distance at 500 µm from the scleral spur, anterior chamber angle and iris convexity between the two groups (all P > 0.05). AL, LT, IT, TCA and CBT were positively associated with age (all P < 0.001), while LV and SFCT were negatively associated with age (P = 0.027 and P < 0.001, respectively). Conclusions: Compared with elderly patients, younger PACD patients had more anteriorly positioned lenses, thinner and more anteriorly rotated ciliary bodies, thicker choroids, and shorter axial length. These characteristics might be important anatomical bases for the earlier onset of PACD and the higher risk of malignant glaucoma after filtering surgery.

Twitter-based analysis reveals differential COVID-19 concerns across areas with socioeconomic disparities.

OBJECTIVE: We sought to understand spatial-temporal factors and socioeconomic disparities that shaped U.S. residents' response to COVID-19 as it emerged. METHODS: We mined coronavirus-related tweets from January 23rd to March 25th, 2020. We classified tweets by the socioeconomic status of the county from which they originated with the Area Deprivation Index (ADI). We applied topic modeling to identify and monitor topics of concern over time. We investigated how topics varied by ADI and between hotspots and non-hotspots. RESULTS: We identified 45 topics in 269,556 unique tweets. Topics shifted from early-outbreak-related content in January, to the presidential election and governmental response in February, to lifestyle impacts in March. High-resourced areas (low ADI) were concerned with stocks and social distancing, while under-resourced areas shared negative expression and discussion of the CARES Act relief package. These differences were consistent within hotspots, with increased discussion regarding employment in high ADI hotspots. DISCUSSION: Topic modeling captures major concerns on Twitter in the early months of COVID-19. Our study extends previous Twitter-based research as it assesses how topics differ based on a marker of socioeconomic status. Comparisons between low and high-resourced areas indicate more focus on personal economic hardship in less-resourced communities and less focus on general public health messaging. CONCLUSION: Real-time social media analysis of community-based pandemic responses can uncover differential conversations correlating to local impact and income, education, and housing disparities. In future public health crises, such insights can inform messaging campaigns, which should partly focus on the interests of those most disproportionately impacted.

Weighted gene coexpression network reveals downregulation of genes in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious lung disease observed in premature infants, known to cause considerable morbidity and mortality. Its prognosis is influenced by a complex network of genetic interactions. In this study, we determined the potential key factors in the pathogenesis of this condition. METHODS: We constructed scale-free gene coexpression network using weighted gene coexpression network analysis. The analysis was carried out on the GSE8586 dataset, which contains the expression profiles of umbilical cord tissue homogenates from 20 neonates with BPD and 34 unaffected controls. RESULTS: Our analysis identified one significantly downregulated coexpression module related to the BPD phenotype. It was significantly enriched in genes related to human T-cell leukemia virus infection and the mitogen-activated protein kinase pathway. In this module, the expression of the following four hub genes in infants with BPD was significantly decreased: Fos proto-oncogene (FOS), BTG antiproliferation factor 2 (BTG2), Jun proto-oncogene (JUN), and early growth response protein 1 (EGR1). The downregulation of these hub genes was verified in clinical samples derived from blood and umbilical cord tissue. CONCLUSION: The decreased expression of FOS, BTG2, JUN, and EGR1 is associated with BPD and, therefore, could be used as biomarkers to diagnose early BPD.

Impaired systemic vascular endothelial function in patients with non-arteritic anterior ischaemic optic neuropathy.

PURPOSE: The purpose of this study was to evaluate systemic endothelial function in elderly hypertension patients with non-arteritic anterior ischaemic optic neuropathy (NAION) by using a noninvasive physiological method: endothelium-dependent, flow-mediated vasodilation (FMD). METHODS: Forty-two systemic hypertension patients with NAION (NAION group), 64 age- and sex-matched patients with systemic hypertension and no other ocular disease (hypertension group), and 100 age- and sex-matched healthy volunteers (normal group) were enrolled. FMD was evaluated using a high-resolution ultrasonography. Traditional cardiovascular risk factors and vascular parameters were measured. RESULTS: Systolic blood pressure and diastolic blood pressure were significantly higher in patients with NAION compared with the control groups (p < 0.001). The FMD decreased significantly in the NAION group (6.02 ± 1.87 %) compared to in the hypertension group (7.86 ± 2.94 %, p < 0.001) and the normal group (8.99 ± 2.44 %, p < 0.001). By multivariable logistic regression analysis, FMD was significantly associated with NAION (OR, 1.79; 95%CI, 1.67-2.01). CONCLUSIONS: NAION may be associated with systemic vascular endothelial dysfunction. FMD might be useful in the treatment monitoring of NAION.

Factors influencing improvement of visual field after trans-sphenoidal resection of pituitary macroadenomas: a retrospective cohort study.

AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans-sphenoidal surgery. Ophthalmologic evaluation, best-corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23±1.29y. Ninety-three patients were female and 108 were male. The mean tumor volume was 14.36±6.23 cm(3). The mean duration of preoperative symptoms was 11.50±0.88mo. Mean preoperative MD was -17.50±0.82 dB. Mean Preoperative visual acuity was 0.64±0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans-sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/ Ki-67.

Contrast-enhanced ultrasound for evaluation of renal trauma during acute hemorrhagic shock: a canine model.

PURPOSE: Contrast-enhanced ultrasound (CEUS) is a highly specific and sensitive method for assessing hemodynamically stable patients with blunt abdominal trauma. We evaluated the efficacy of CEUS in assessing renal trauma in different states of hemodynamic instability or shock. METHODS: Hemorrhagic renal lesions reflecting grade III-IV trauma were established in the kidneys of 25 mongrel dogs. Mild, moderate, and severe systemic hypotension was induced by controlled exsanguination. The features of renal trauma in CEUS and contrast-enhanced computed tomography (CECT) were assessed and compared before shock and during shock progression. RESULTS: Gross pathology showed that with trauma, the kidneys gradually shrank and became soft, and the active bleeding in the area of the renal trauma gradually reduced and stopped. No significant differences were observed in the trauma detection rates between CEUS and CECT at any stage of shock. During the baseline and mild shock stage, sonograms obtained after intravenous injection of contrast agent showed marked contrast medium extravasation and pooling at the site of active bleeding. With shock progression, the difference in enhancement between trauma areas and the surrounding renal tissue decreased: the trauma areas became indistinct and the abnormal enhancement associated with active bleeding diminished. Further, CEUS enabled visualization of changes in renal perfusion associated with shock progression. Changes in contrast agent arrival time and the time to peaking were observed earliest in the mild shock model. The contrast agent peak intensity reduced, while the washout time increased as shock progressed from moderate to severe. CONCLUSION: In our canine model, CEUS was found to be as accurate as CECT in assessing hemorrhagic renal lesions. Thus, CEUS seems a promising tool for monitoring hemodynamic changes and predicting early shock to enable the conservative treatment of severe renal trauma.

[Contrast-enhanced ultrasound for the signature analysis of splenic trauma in a canine model during hemorrhagic shock and resuscitation].

OBJECTIVE: To conduct signature analysis for splenic trauma in canines during hemorrhagic shock and resuscitation by contrast enhanced ultrasonography (CEUS). METHODS: Forty grade III-IV traumatic splenic lesions were established in 15 mongrel dogs. Hemorrhagic shock was induced in these animals by using the modified Wiggers's method. Animals in shock were then resuscitated with 6% hydroxyethyl starch. The features of splenic trauma during hemorrhagic shock or resuscitation were assessed by CEUS, which were compared with the data collected by contrast-enhanced computed tomography (CECT). Acoustic quantification of CEUS was performed to assess splenic blood perfusion in different stages. RESULTS: There was no significant difference in detection rate between CEUS and CECT during hemorrhagic shock and resuscitation. Before hemorrhagic shock, there were 40 traumatic bleeding lesions and 85% of them were revealed by CEUS (34/40). With the progress in shock, CEUS revealed that the numbers of tiny branches of splenic arteries were decreased, which became thinner with no active bleeding. After fluid resuscitation, rebleeding was occurred in 30 traumatic lesions, and 28 (93.3%) of them were captured by CEUS. CEUS could also visualize the changes in splenic perfusion in different stages. During the shock, the arrival time (AT), time to peak intensity (TTP), peak intensity (PI) were significantly lower and the washout time (WT) were significantly higher than those at other stages (P<0.01). CONCLUSION: CEUS not only can dynamically monitor the changes in spleen traumatic hemorrhage and recurrent hemorrhage, but also can quantitatively study the changes in spleen blood perfusion in different stages.

Intravenous flurbiprofen for post-thymectomy pain relief in patients with myasthenia gravis.

BACKGROUND: Post-thymectomy pain in myasthenia gravis (MG) patients can inhibit breathing and coughing. Inappropriate usage of analgesics may exacerbate respiratory inhibition and even cause myasthenic crisis. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used to control moderate postoperative pain and is not associated with respiratory inhibition. We hypothesized that flurbiprofen may provide post-thymectomy pain relief without increasing the risk of complications in MG patients. METHODS: Two hundred MG patients underwent extended thymectomy from March 2006 to December 2010 and were randomly allocated to a flurbiprofen group (110 patients, 50 mg intravenous flurbiprofen axetil) or a control group (90 patients, 100 mg intramuscular tramadol) as postoperative analgesia. Visual analog scale (VAS) pain score, heart rate, blood pressure, respiratory rate, pulse oximetry (SpO2), and adverse effects were recorded before and up to 24 h after drug administration. RESULTS: There were no significant differences in the preoperative clinical characteristics of the flurbiprofen and control (tramadol) groups. Both flurbiprofen and tramadol significantly alleviated post-thymectomy pain (p<0.05 for both), but patients in flurbiprofen group had significantly lower VAS pain scores at 0.5 h, 2 h, 4 h, and 8 h after surgery (p<0.05 for all times). There were no significant post-thymectomy changes of heart rate, respiratory rate, mean arterial blood pressure, or SpO2 in either group at all time points. CONCLUSIONS: Post-thymectomy intravenous administration of flurbiprofen axetil provides safe and effective analgesia for MG patients.

Late-onset lens particle glaucoma as a consequence of posterior capsule rupture after pars plana vitrectomy.

PURPOSE: To report the treatment of late-onset lens particle glaucoma associated with posterior capsule rupture during pars plana vitrectomy. METHODS: Case report. RESULTS: A 33-year-old man had severe pain and impaired vision in the left eye after vitrectomy, associated with white fleck-like particles circulating in the anterior chamber. The intraocular pressure (IOP) was 38 mmHg. The anterior lens capsule was intact, however, lens particle glaucoma was diagnosed by the slit-lamp examination, B-mode ultrasonography and ultrasound biomicroscopy (UBM). The lens material was removed by irrigation-aspiration after the patient remained face down for two hours to facilitate precipitation of the lens material from the vitreous into the anterior chamber. IOP after the procedure was 21 mmHg. CONCLUSION: Posterior lens capsule may be disrupted during vitrectomy. Although the anterior lens capsule is intact, lens particle glaucoma should be considered when IOP increases with particulate matter circulating in the anterior chamber. Surgical removal of this material may be sufficient to control IOP without the need for additional glaucoma surgery.

Different patterns of NF-κB and Notch1 signaling contribute to tumor-induced lymphangiogenesis of esophageal squamous cell carcinoma.

BACKGROUND: Lymph node involvement and tumor-induced lymphangiogenesis appear as the earliest features of esophageal squamous cell carcinoma (ESCC), although the molecular regulatory mechanisms involved have remained unclear. Our aim was to investigate the contribution of NF-κB and Notch1 signaling to lymph node involvement and tumor-induced lymphangiogenesis in ESCC. MATERIAL AND METHODS: NF-κB and Notch1 expression in 60 tissue samples of ESCC were assessed by immunohistochemical staining. The correlations of NF-κB and Notch1 with lymph node involvement, lymphatic vessel density (LVD), podoplanin, and vascular endothelial growth factor-C (VEGF-C) were further evaluated to determine the association of NF-κB and Notch1 expression with tumor-induced lymphangiogenesis. RESULTS: Chi-square tests revealed that NF-κB and Notch1 expression in ESCC tissues were significant associated with lymph node metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF-κB, but weak expression of Notch1, was observed in tumor tissues with lymph nodes involvement (P < 0.05 for both). The mean histoscores of LVD, podoplanin, and VEGF-C staining were higher in high-NF-κB-expressing tissue than in low-expressing tissue (P < 0.05 for each). In contrast, the mean histoscores of LVD and VEGF-C staining were lower in high-Notch1-expressing tissue than in low-expressing tissue (P < 0.05 for both). A multiple factors analysis of LVD and VEGF-C further demonstrated that LVD and VEGF-C status were significantly correlated with NF-κB and Notch1 expression in tumors. NF-κB and Notch1 expression were also significantly inversely correlated (P < 0.05). CONCLUSION: These results suggest that different patterns of NF-κB and Notch1 signaling contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC, and reveal that up-regulation of NF-κB is associated with down-regulation of Notch1 in tumor tissue.