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.

CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.

SOX9 Induces Orbital Fibroblast Activation in Thyroid Eye Disease Via MAPK/ERK1/2 Pathway.

Purpose: To evaluate the expression of sry-box transcription factor 9 (SOX9) in orbital fibroblasts (OFs) of thyroid eye disease (TED) and to find its potential role and underlying mechanism in orbital fibrosis. Methods: OFs were cultured from orbital connective tissues obtained from patients with TED (n = 10) and healthy controls (n = 6). SOX9 was depleted by small interfering RNA or overexpressed through lentivirus transduction in OFs. Fibroblast contractile activity was measured by collagen gel contraction assay and proliferation was examined by EdU assay. Transcriptomic changes were assessed by RNA sequencing. Results: The mRNA and protein levels of SOX9 were significantly higher in OFs cultured from patients with TED than those from healthy controls. Extracellular matrix-related genes were down-regulated by SOX9 knockdown and up-regulated by SOX9 overexpression in TED-OFs. SOX9 knockdown significantly decrease the contraction and the antiapoptotic ability of OFs, whereas the overexpression of SOX9 increased the ability of transformation, migration, and proliferation of OFs. SOX9 knockdown suppressed the expression of phosphorylated ERK1/2, whereas its overexpression showed the opposite effect. Epidermal growth factor receptor (EGFR) is one of the notably down-regulated genes screened out by RNA sequencing. Chromatin immunoprecipitation-qPCR demonstrated SOX9 binding to the EGFR promoter. Conclusions: A high expression of SOX9 was found in TED-OFs. SOX9 can activate OFs via MAPK/ERK1/2 signaling pathway, which in turn promotes proliferation and differentiation of OFs. EGFR was a downstream target gene of SOX9. SOX9/EGFR can be considered as therapeutic targets for the treatment of orbital fibrosis in TED.

Long-Term Visual Quality and Pupil Changes after Small-Incision Lenticule Extraction for Eyes without Preoperative Cylinder Refraction.

Purpose: To investigate the long-term changes in visual quality and pupil size after small incision lenticule extraction (SMILE) for eyes without preoperative cylinder refraction. Methods: Thirty-three myopic eyes (33 patients) without preoperative cylinder refraction were corrected using SMILE. Refractive outcomes, corneal curvature, aberrations, contrast sensitivity (CS), and pupil diameter were evaluated preoperatively, and 30 months postoperatively. Results: The 30-month postoperative uncorrected and corrected distance visual acuity (UDVA and CDVA, LogMAR) were -0.10 ± 0.09 and -0.14 ± 0.06, respectively, whereas the preoperative CDVA (LogMAR) was -0.07 ± 0.05. Cylinder refraction of -0.11 ± 0.21 D (ranging from -0.50 to 0.00) was observed at 30 months postoperatively, increasing from the preoperative cylinder refraction of 0.00 ± 0.00 D (P=0.004). Moreover, the centroid coordinates x, y of corneal anterior astigmatic vectors were -0.19 ± 0.22, 0.81 ± 0.33 at 30 months postoperatively, and 0.02 ± 0.28, 0.76 ± 0.51 preoperatively (Px < 0.001 and Py=0.810, respectively). Furthermore, a 15° axis change in the mean anterior corneal astigmatic vector was observed at 30 months postoperatively from the preoperative state, as measured by Pentacam. At 30 months postoperatively, the photopic Log CS reduced significantly with glare at three and six cycles/degrees (P < 0.001 and P=0.015, respectively), a decreased photopic pupil diameter (3.27 ± 0.55 mm vs. 3.10 ± 0.66 mm, P=0.030), and an increased Coma (Z31) and Trefoil (Z3-3) at 4 mm diameter area analysis. However, a significant linear regression relationship was only observed between changes in photopic pupil diameter and changes in photopic Log CS with glare at 12 cycles/degree (P=0.038 and ß = 0.282). Conclusion: Slight cylinder regression was observed with thicker corneal lenticular extraction after SMILE correction of nonastigmatic eyes 30 months postoperatively. This regression was mainly because of the axis changes in anterior corneal astigmatism power. Therefore, a cylinder nomogram modification of 0.25 to 0.50 D is considerable for correcting nonastigmatic myopic eyes with a predicted spherical lenticular thickness over 100 µm.

Standard ophthalmology residency training in China: an evaluation of resident satisfaction on training program in Guangdong Province.

BACKGROUND: National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. METHOD: A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P < 0.05 was considered statistically significant. RESULTS: A total of 471/635 (74.17%) valid questionnaires were returned from all the STRD bases of Guangdong Province, which included 38 hospitals. 60.3% of the respondents reported overall satisfaction with their training. The satisfaction with operative teaching (60.7%) was slightly lower than the other settings of teaching experience (above 65%). Meanwhile, the satisfaction on different secessions of operative experience was all below 70%, of which in the areas of cornea and orbit were 55.42% and 57.53%, respectively. Some potential factors were found to affect general satisfaction, including the training grade, marriage, working time, income level, the doctor-patient relationship, family members working as doctors, the time proportion spent on writing medical documents during clinical work, and the frequency of attending academic meetings. Improvement was observed in both performing and reporting clinical examinations in the last year of training in comparison to the first year. Finally, 82.8% of the residents acknowledged this training was helpful for future clinical work. The first five career preferences for residents were cataract (67.1%), refractive surgery (42.3%), vitreo-retina (36.5%), optometry (28.7%), and oculoplastic (27.2%). CONCLUSION: Ophthalmology residents in Guangdong Province expressed comparable satisfaction with the STRD program. To further improve satisfaction, factors such as resident subsidy, harmonious marriage, the patient-doctor relationship, and chances of attending academic conferences should be emphasized.

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.

Reconstructing auto tissue engineering lamellar cornea with aspartic acid modified acellular porcine corneal stroma and preconditioned limbal stem cell for corneal regeneration.

Tissue engineering cornea has shown great clinical potential for cornea reconstruction, but efficient recovery of natural structure and physiological function remains great challenges. In this study, the acellular porcine corneal stroma (APCS) was prepared by a phospholipase A2 decellularization method and further crosslinked with aspartic acid (Asp). The modified APCS-Asp scaffold showed significant increase of hydration degree, ultrastructure regularity, corneal viscoelasticity and anti-degradation ability compared to APCS. Autologous rabbit limbal tissue was pre-treated by tumor necrosis factor-alpha (TNF-α) and collagenase IV, and the pretreated primary limbal stem cells (LSCs) were cultured with embryonic stem cells conditioned medium (ESCM), and LSCs showed 3D cell sphere structure and improved stem cell properties compared to the control group. The auto-tissue engineering lamellar cornea (ATELC) was quickly reconstructed by using peptide hydrogel with a dynamic culture system. With intact and functional epithelial cell layer, the reconstructed ATELC quickly recovered natural optical characteristics 1 week post transplantation in the rabbit lamellar keratoplasty model and satisfying neural regrowth as well as favorable stromal repopulation were observed in the transplanted eyes in the 6 months following up post-surgery. In summary, this study provides a comprehensive optimized reconstruction strategy for ATELC, which maybe similar medical application to natural cornea.

Tear film cytokines as prognostic indicators for predicting early recurrent pterygium.

Cytokine profiles in tears have become a noninvasive biomarker for various ocular surface diseases. Therefore, the preoperative profile of cytokines in tear samples of 89 primary pterygium patients were obtained from Zhongshan Ophthalmic Center during 2015-2017. Compared to the tear cytokines in primary groups, the concentrations of IL-8, MMP-1, MMP-9, bFGF and VEGF were generally higher in recurrent pterygium group. The five cytokines were used to build diagnostic models by multiple machine learning algorithms, which can accurately distinguish non-recurrent and recurrent samples of primary pterygium patients. Besides, these cytokines were significantly associated with Recurrent-free survival (RFS) time in pterygium patients and further applied to develop a prognostic model which can estimate the prognosis of pterygium after resection. Afterward, a novel nomogram combined risk score of cytokines related biomarker and clinical characteristics was constructed, which manifested ideal accuracies to predict the 1 and 2 years' probability of pterygium recurrent events. Thus, our finding provides a more simple and accurate prediction for early pterygium recurrence after resection. It also affords a useful tool for ophthalmologists to choose the optimal treatment strategies for pterygium patients.

High Expression of EZH2 Mediated by ncRNAs Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by a complex regulatory network. Increasing evidence suggests that an abnormal gene expression of EZH2 is associated with HCC progression. However, the molecular mechanism by which non-coding RNAs (ncRNAs) regulate EZH2 remains elusive. METHODS: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to perform differential expression analysis and prognostic analysis. We used the Encyclopedia of RNA Interactomes (ENCORI) database to predict candidate miRNAs and lncRNAs that may bind to EZH2. Subsequently, the comprehensive analysis (including expression analysis, correlation analysis, and survival analysis) identified ncRNAs that contribute to EZH2 overexpression. RESULTS: EZH2 was found to be upregulated in the majority of tumor types and associated with a poor prognosis. Hsa-miR-101-3p was identified as a target miRNA of EZH2. Additionally, SNHG6 and MALAT1 were identified as upstream lncRNAs of hsa-miR-101-3p. Meanwhile, correlation analysis revealed that EZH2 expression was significantly associated with the infiltration of several immune cell types in HCC. CONCLUSION: SNHG6 or MALAT1/hsa-miR-101-3p/EZH2 axis were identified as potential regulatory pathways in the progression of HCC.

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.

Rare cause of left eye floaters and blurred vision in an immunocompromised patient: acute retinal necrosis (ARN).

Acute retinal necrosis (ARN) is a clinical syndrome featuring severe vitritis and occlusive vasculitis characterised by full thickness necrotising retinitis. ARN is usually caused by an acute infection by either varicella zoster virus or herpes simplex virus, rarely cytomegalovirus (CMV). ARN often occurs in healthy adults; occasionally affecting immunocompromised patients with poor prognosis including significant visual loss and detachment of the atrophic retina regardless of antiviral treatment. We presented a man in his early 30s with a history of left eye floaters and blurred vision. He was diagnosed with T-cell acute lymphoblastic leukaemia 1 year ago and treated with chemotherapy and allogenic haematopoietic stem cell transplant 5 months ago. His clinical diagnosis was left eye ARN caused by acute viral infection with CMV being the most likely cause, which is rarely seen in immunocompromised patients. Our case highlighted a diagnostic and therapeutic challenge in the absence of guideline or evidence-based literature to follow.

Multiparametric quantitative MRI for the evaluation of dysthyroid optic neuropathy.

OBJECTIVE: To evaluate the ability of quantitative MRI parameters for predicting dysthyroid optic neuropathy (DON). METHODS: We retrospectively collected and analyzed the clinical features and 3.0 T MRI data of 59 patients with Graves orbitopathy (GO), with (n = 26) and without DON (n = 33). We compared MRI quantitative parameters, including the modified muscle index (mMI), proptosis, volume of intra-orbital fat, mean apparent diffusion coefficient value, and T2 value of the optic nerve among patients with and without DON. A logistic regression analysis was performed to identify the risk factors associated with DON. Moreover, we performed a receiver operating characteristic curve analysis and decision curve analysis to evaluate the diagnostic performance of the identified parameters for DON. RESULTS: We studied 118 orbits (43 and 75 with and without DON, respectively). The mMI and mean T2 value of the optic nerve were significantly greater in orbits with DON (p < 0.001). A greater mMI at 21 mm (odds ratio (OR), 1.039; 95% confidence interval (CI): 1.019, 1.058) and higher mean T2 value of the optic nerve (OR, 1.035; 95% CI: 1.017, 1.054) were associated with a higher risk of DON. A model combining the mMI at 21 mm and mean T2 values for the optic nerve effectively predicted DON in patients with GO, with a sensitivity and specificity of 95.3% and 76%, respectively. CONCLUSION: A quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve can be an effective imaging marker for identifying DON. KEY POINTS: • Patients with GO and DON had greater mMI than those without DON. • Optic nerves in patients with DON demonstrated an increased T2 value. • The quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve is the most effective method for diagnosing DON.

Visual Impairments Are Associated With Retinal Microvascular Density in Patients With Parkinson's Disease.

OBJECTIVE: This study aimed to evaluate retinal microvascular density in patients with Parkinson's disease (PD) and its correlation with visual impairment. METHODS: This cross-sectional study included 24 eyes of 24 patients with PD and 23 eyes of 23 healthy controls. All participants underwent ophthalmic examination, visual evoked potential (VEP) test, 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), and optical coherence tomography angiography (OCTA) examination. The correlation between retinal microvascular density and visual parameter was evaluated using Spearman correlation analysis, and the area under receiver operating characteristic curve (AUROC) was calculated. RESULTS: Parkinson's disease patients had prolonged P100 latency (P = 0.041), worse vision-related quality of life (composite score and 3 of 12 subscales in NEI VFQ-25), and decreased vessel density (VD) in all sectors of 3-mm-diameter region (all P < 0.05) compared with healthy controls. There were no statistical differences in the ganglion cell-inner plexiform layer (GCIPL) thickness and retinal nerve fiber layer (RNFL) thickness between the two groups. A negative correlation was found between P100 latency and nasal and superior sectors of macular VD in a 3-mm-diameter region (r = -0.328, P = 0.030; r = -0.302, and P = 0.047, respectively). Macular VD in a 3-mm-diameter region showed diagnostic capacities to distinguish PD patients from healthy controls (AUROCs, ranging from 0.655 to 0.723). CONCLUSION: This study demonstrated that decreased retinal microvascular density was correlated with visual impairment in PD patients. Retinal microvasculature change may occur earlier than visual decline and retinal structure change and has the potential to be a promising diagnostic marker for early PD.

The Role of Elastase in Corneal Epithelial Barrier Dysfunction Caused by Pseudomonas aeruginosa Exoproteins.

Purpose: To investigate the role of elastase in corneal epithelial barrier dysfunction caused by the exoproteins secreted by Pseudomonas aeruginosa. Methods: Exoproteins obtained from Pseudomonas aeruginosa culture supernatant were analyzed by shotgun proteomics approach. In vitro multilayered rabbit corneal epithelial barrier model prepared by air-liquid interface technique (CECs-ALI) were treated with 2 µg/ml exoproteins and/or 8 mM elastase inhibitor. Then the epithelial barrier function was evaluated by transepithelial electrical resistance (TEER) assay and tight junction proteins immunofluorescence. Cell viability and the apoptosis rate were examined by CCK8 assay and flow cytometry. TNF-α, IL-6, IL-8, and IL-1ß levels were measured by ELISA. Mice cornea treated with exoproteins and/or elastase inhibitor were evaluated in vivo and in vitro. Results: Elastase (24.2%) is one of the major components of exoproteins. After 2 µg/ml exoproteins were applied to CECs-ALI for two hours, TEER decreased from 323.2 ± 2.7 to 104 ± 6.8 Ω/cm2 (P < 0.001). The immunofluorescence results showed a distinct separation in tight junction and significant degradation of ZO-1 and occludin (P < 0.05). Elastase inhibitor (8 mM) alleviated the decrease in TEER value (234 ± 6.8 Ω cm2) induced by exoproteins. Inhibition of elastase decreased the apoptosis rate of CECs treated with exoproteins from 30.2 ± 3.8% to 7.26 ± 1.3% and the levels of inflammatory factors (P < 0.05). Mice corneal epithelium defect could be induced by exoproteins and protected by elastase inhibitor. Conclusions: Elastase plays a critical role in corneal epithelial barrier dysfunction caused by Pseudomonas aeruginosa exoproteins via damaging tight junctions. The inhibition of elastase could protect the corneal epithelial barrier via reducing virulence and inflammation.

Utility of multi-parametric quantitative magnetic resonance imaging of the lacrimal gland for diagnosing and staging Graves' ophthalmopathy.

PURPOSE: To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) based on multi-parametric quantitative MRI and its clinical utility in LG diagnosis and activity in GO. METHODS: We enrolled 99 consecutive patients with GO (198 eyes) and 12 Graves' Disease (GD) patients (24 eyes) from July 2018 to June 2020. Clinical, laboratory, and MRI data were collected at the first visit. Based on clinical activity scores, eyes with GO were subdivided into active and inactive groups. T2-relaxation time (T2) and the absolute reduction in T1-relaxation time (ΔT1) were determined. After MRI and processing, we performed descriptive data analysis and group comparisons. Novel logistic regression predictive models were developed for diagnosing and staging GO. Diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis. RESULTS: LG in GO group had significantly higher T2 and ΔT1 values than the GD group [106.25(95.30,120.21) vs. 83.35(78.15,91.45), P<0.001, and 662.62(539.33,810.95) vs. 547.35(458.62,585.57), P = 0.002, respectively]. The GO group had higher T2 of LG indicating higher disease activity [110.93(102.54,127.67) vs. 93.29(87.06,101.96), P < 0.001]. Combining T2 and ΔT1 values of LG, Model I had higher diagnostic value for distinguishing GO from GD (AUC=0.94, 95 %CI: 0.89,0.99, P<0.001). Meanwhile, T2 of LG had higher diagnostic value for grading GO activity (AUC = 0.84, 95 %CI: 0.76,0.92, P<0.001). CONCLUSIONS: Multi-parametric quantitative MRI parameters of the LG in GO were significantly altered. Novel models combining LG T2 and ΔT1 values showed excellent predictive performances in diagnosing GO. Furthermore, T2 of LG showed practical utility for staging GO.

Corneal Endothelium: A Promising Quantitative Index for Graves Ophthalmopathy Activity Evaluation.

PURPOSE: To investigate the corneal endothelium damage in Graves ophthalmopathy (GO) and its role as a promising quantitative index to evaluate GO activity. DESIGN: Cross-sectional study. METHODS: This study included 128 eyes of 64 patients with GO. All subjects underwent ophthalmologic examinations, including proptosis, tear break-up time (BUT), corneal fluorescein staining, and Schirmer test. Corneal endothelium was measured by noncontact specular microscope and ocular biometric parameters were measured by IOLMaster 700. Each eye was assigned a specific clinical activity score (CAS), then grouped as active (CAS ≥3 points) or inactive (CAS <3 points). Ocular parameters between the 2 groups were compared using generalized estimating equations accounting for inter-eye correlation, and receiver operating characteristic (ROC) curves were also obtained. Main outcome measures were parameters of corneal endothelium. RESULTS: Among the included eyes, 81 eyes had inactive GO and 47 eyes had active GO. Corneal endothelial cell morphology was altered in active GO compared with inactive GO. The coefficient variation of cell area (CV) was significantly higher in active GO compared with inactive GO (37.0 [34.4-41.2]% vs 33.9 [30.9-36.8]%, P = .001), and positively correlated with CAS (r = 0.322, P < .001). Moreover, CV showed a diagnostic capacity to differentiate the active eyes from inactive eyes. The area under the ROC curve was 0.705. CONCLUSIONS: Active GO had morphologic changes in corneal endothelium compared with inactive GO. CV is a sensitive indicator to reflect corneal endothelial function, and has the potential to be adopted as a noninvasive, objective, and quantitative index for evaluating the activity status of GO patients.

Bacterial agents and changes in drug susceptibilities in cases of chronic dacryocystitis, Southern China.

PURPOSE: This study aimed to determine the susceptibility and the changes of bacterial agents of chronic dacryocystitis and determine the risk factors for bacterial prevalence and drug sensitivity to provide a reference for clinical selection of antibiotics. METHODS: A case-control study was conducted using 112 patients with chronic dacryocystitis and 112 patients with non-infectious ophthalmopathy between August 2017 and April 2018. Lacrimal and conjunctival sac secretions were cultured for aerobic and anaerobic bacteria. Forty-five patients with chronic dacryocystitis between November 2014 and November 2015 were also included. RESULTS: Positive bacterial cultures were obtained from 61.9% and 50.9% of chronic dacryocystitis and non-infectious ophthalmopathy patients, but the detection rates for pathogenic bacteria were 18.3% and 2.7%, respectively (P > 0.001). Gram-negative and anaerobic bacteria were significantly more prevalent in the patient group compared with the control group (P = 0.001 and 0.005, respectively). Bacteria were detected at a significantly higher rate in patients with irritant symptoms (itch or foreign-body sensation) than in those without (OR = 9.333, P = 0.002), particularly Staphylococcus (OR = 9.783, P = 0.002). 11.6% (10/86) and 55.8% (48/86) showed resistance to levofloxacin and tobramycin, respectively. Compared with three years ago, the detection rate for Gram-positive cocci decreased from 51.1% to 27.8% (χ2 = 8.054, P = 0.005) CONCLUSIONS: Gram-positive cocci, Gram-negative bacilli, and anaerobic bacteria were the predominant pathogens. The prevalence of Gram-positive bacteria in cases of chronic dacryocystitis is decreasing.

The Key Role of VEGF in the Cross Talk between Pterygium and Dry Eye and Its Clinical Significance.

PURPOSE: To examine whether dry eye severity is a risk factor for pterygium activity and whether vascular endothelial growth factor (VEGF) is crucial in the cross talk between pterygium and dry eye. METHODS: A total of 103 patients with primary pterygium (Pteg) were included in the study group; they were divided into 2 groups according to the complication of dry eye (DE) (Pteg + DE group, Pteg - DE group). Further, 60 patients with just dry eye (DE group) and 60 normal individuals (normal) were included as 2 control groups. DE severity and pterygium activity were measured, and unstimulated tear samples and pterygium tissues were collected for cytokine detection. RESULTS: (1) Tear detection: VEGF expression increased in the Pteg + DE group compared to the Pteg - DE, DE, and normal control groups; VEGF was especially increased in the active Pteg + DE group. VEGF concentration was positively correlated with pterygium activity. (2) Tissue detection: the mRNA expression of VEGF was upregulated in the active pterygium group. CONCLUSIONS: Inflammation played an important role in the development of dry eye and pterygium. VEGF was the core molecule in the cross talk, which might explain the high incidence of the coexistence of these 2 diseases.

Treatment with solubilized Silk-Derived Protein (SDP) enhances rabbit corneal epithelial wound healing.

There is a significant clinical need to improve current therapeutic approaches to treat ocular surface injuries and disease, which affect hundreds of millions of people annually worldwide. The work presented here demonstrates that the presence of Silk-Derived Protein (SDP) on the healing rabbit corneal surface, administered in an eye drop formulation, corresponds with an enhanced epithelial wound healing profile. Rabbit corneas were denuded of their epithelial surface, and then treated for 72-hours with either PBS or PBS containing 5 or 20 mg/mL SDP in solution four times per day. Post-injury treatment with SDP formulations was found to accelerate the acute healing phase of the injured rabbit corneal epithelium. In addition, the use of SDP corresponded with an enhanced tissue healing profile through the formation of a multi-layered epithelial surface with increased tight junction formation. Additional biological effects were also revealed that included increased epithelial proliferation, and increased focal adhesion formation with a corresponding reduction in the presence of MMP-9 enzyme. These in vivo findings demonstrate for the first time that the presence of SDP on the injured ocular surface may aid to improve various steps of rabbit corneal wound healing, and provides evidence that SDP may have applicability as an ingredient in therapeutic ophthalmic formulations.

Corticosteroids effects on LPS-induced rat inflammatory keratocyte cell model.

PURPOSE: Corticosteroids are efficient anti-inflammation treatments. However, there are still arguments on whether it should be used in keratitis. This study was to observe the effect of corticosteroids on keratocytes both in normal condition and inflammation status in vitro. METHODS: Rat keratocytes were cultured and used for examination. 10 µg/ml lipopolysaccharide (LPS) was used to establish the inflammatory keratocyte cell model, and prednisolone acetate (PA), dexamethasone (Dex) and fluorometholone (Flu) were used as corticosteroids treatments. 5 d-growth curve and cell viabilities were assayed by CCK8, and cell morphologies and migration rate were studied. TNF-α, IL-6 and IL-1ß levels were examined by ELISA. Western blotting was used to quantified type VI collagen (Col VI) and matrix metalloproteinase 9 (MMP9) expressions, and immunofluorescence staining assays of Col I and Col VI were carried out. RESULTS: In normal condition, proliferation and migration of keratocytes were slightly influenced in PA, Dex and Flu groups. The secretion of Col I and Col VI was suppressed and MMP9 expression increased in corticosteroids groups. But no significant difference was seen in TNF-α, IL-6 and IL-1ß expression levels. In inflammatory status, TNF-α, IL-6 and MMP9 levels increased in LPS group, while they significantly decreased in corticosteroids groups. Although keratocytes viabilities and migration were slightly affected in 24 h, no significant differences were seen between LPS group and corticosteroids groups in 5-d proliferation. Col I and Col VI secretion in LPS-keratocytes was maintained with corticosteroids treatments. CONCLUSIONS: Corticosteroids showed lightly effects on keratocytes proliferation and migration, but it successfully decreased TNF-α, IL-6 level and maintained the secretion of and Col I and Col VI, while suppressed the expression of MMP9 in LPS-induced keratocytes. PA was suggested to use in early stage of keratitis clinical treatment.