Association between gut microbiota and central retinal artery occlusion: A two-sample Mendelian randomization study.

PURPOSE: The gut microbiota might be closely related to central retinal artery occlusion (CRAO), but the causality has not been well defined. Two-sample Mendelian randomization (MR) study was used to reveal the potential causal effect between the gut microbiota and CRAO. METHODS: Data for gut microbiota were obtained from the genome-wide association studies of the Dutch Microbiome Project (DMP) (n = 7738) and the MiBioGen consortium (n = 18,340), and data on CRAO were obtained from samples of FinnGen project (546 cases and 344,569 controls). Causalities of exposures and outcomes were explored mainly using the inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median (WM), simple mode, weighted mode, and MR Pleiotropy RESidual Sum and Outlier were simultaneously applied to validate the final results. RESULTS: We identified three microbial pathways (two risk factors/one protective factor) and seven microbial taxa (two risk factors/five protective factors) associated with CRAO in the DMP study. Based on the data from the MiBioGen consortium, we identified seven microbial taxa (two risk factors/five protective factors) associated with CRAO, including the Eubacterium genus, which was consistently identified as a risk factor in both the DMP and the MiBioGen consortium MR analyses. CONCLUSION: Our study implicates the potential causal effects of specific microbial taxa and pathways on CRAO, potentially providing new insights into the prevention and treatment of CRAO through specific gut microbial taxa and pathway. Since our conclusion is a hypothesis derived from secondary genome-wide association studies (GWAS) data analysis, further research is needed for confirmation.

Retinoblastoma and polydactyly in a child with 46, XY, 15pstk+ karyotype-A case report and literature review.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular malignancy in childhood, originating from primitive retinal stem cells or cone precursor cells. It can be triggered by mutations of the RB1 gene or amplification of the MYCN gene. Rb may rarely present with polydactyly. METHODS: We conducted karyotype analysis, copy number variation sequencing, and whole-genome sequencing on the infant proband and his family. The clinical course and laboratory results of the proband's infant were documented and collected. We also reviewed the relevant literature. RESULTS: A 68-day-old boy presented with preaxial polydactyly and corneal edema. His intraocular pressure (IOP) was 40/19 mmHg, and color Doppler imaging revealed vitreous solid mass-occupying lesions with calcification in the right eye. Ocular CT showed flaky high-density and calcification in the right eye. This was classified as an International Retinoblastoma Staging System group E retinoblastoma with an indication for enucleation. Enucleation and orbital implantation were performed on the child's right eye. Karyotype analysis revealed an abnormal 46, XY, 15pstk+ karyotype, and the mother exhibited diploidy of the short arm of chromosome 15. The Alx-4 development factor, 13q deletion syndrome, and the PAPA2 gene have been reported as potential mechanisms for Rb combined with polydactyly. CONCLUSION: We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

Investigation of Conjunctival Goblet Cell and Tear MUC5AC Protein in Patients With Graves' Ophthalmopathy.

Purpose: The aim of this study was to investigate conjunctival goblet cell density (GCD) and tear mucin-5AC (MUC5AC) protein levels in patients with Graves' ophthalmopathy (GO) and their association with dry eye indicators. Methods: A total of 99 patients with GO (54 active, 45 inactive) and 40 healthy controls were recruited. Comprehensive ophthalmic examinations, including the external eye, ocular surface, GCD, and tear MUC5AC ELISA, were performed. The GCD examination was performed in temporal bulbar conjunctiva, including IVCM GCD by in vivo confocal microscopy (IVCM) and filled GCD of cytokeratin-7 and MUC5AC-positive co-immunomarkers by impression cytology. Tear MUC5AC protein was detected using samples extracted from Schirmer strips. Results: The GO group showed a significant decrease in IVCM GCD, filled GCD, and normalized tear MUC5AC protein compared to controls, with the active GO group showing the greatest decrease (all P < 0.05). Tear MUC5AC protein levels in GO correlated with those of IVCM GCD (r = 0.40, P < 0.001) and filled GCD (r = 0.54, P < 0.001, respectively). Higher ocular surface disease index (r = -0.22, P < 0.05; r = -0.20, P < 0.05; r = -0.21, P < 0.05) and lisamine green staining (r = -0.23, P < 0.05; r = -0.38, P < 0.001; r = -0.42, P < 0.001) were associated with lower tear MUC5AC protein levels, IVCM GCD, and filled GCD, respectively, which decreased with increasing clinical activity score (r = -0.24, P < 0.05; r = -0.28, P < 0.01; r = -0.27, P < 0.01) and conjunctival congestion score (r = -0.27, P < 0.01; r = -0.33, P < 0.001; r = -0.42, P < 0.001). Conclusions: The goblet cell count and tear MUC5AC protein in GO eyes were decreased, possibly due to ocular surface inflammation. Translational Relevance: This study observed the change of tear film mucin in GO patients.

Effects of various extraocular muscle enlargement patterns on muscle diameter index in graves ophthalmopathy patients: a retrospective cohort study.

Graves ophthalmopathy (GO) patients often undergo retrobulbar injection of glucocorticoids (GCs) as a common therapeutic approach. This study aimed to explore the impact of various patterns of extraocular muscle (EOM) enlargement on EOM changes following retrobulbar GCs injection in patients with GO. A retrospective analysis was conducted on GO patients who underwent retrobulbar GCs injections. Data pertaining to EOM diameter (EMD) and muscle diameter index (MDI) were collected from orbital computed tomography (CT) scans. The MDI change (ΔMDI) was calculated by comparing pre- and post-injection MDI values. The relationship between each pre EMD/MDI and ΔMDI was assessed using univariate and multivariate logistic regression analysis. A total of 68 patients with GO were included in this study, accounting for 118 eyes. After retrobulbar injections of GCs, 84 eyes showed a decrease in the MDI, while 34 eyes exhibited an increase in MDI. A threshold effect was observed in the relationship between medial pre EMD/MDI and ΔMDI. When the medial pre EMD/MDI was less than 0.28, a higher medial pre EMD/MDI was associated with a smaller ΔMDI (ß = - 25.21, p = 0.0175). However, when the medial pre EMD/MDI was greater than 0.28, no significant association was found between pre EMD/MDI and ΔMDI. There was a negative correlation between medial + lateral pre EMD/MDI and ΔMDI (ß = - 11.76, p < 0.0189). A higher medial + lateral pre EMD/MDI was associated with a greater decrease in MDI. Additionally, there was a positive correlation between superior rectus muscle-levator complex (SRLC) pre EMD/MDI and ΔMDI (ß = 11.92, p = 0.040). The higher the value of SRLC pre EMD/MDI, the greater the ΔMDI. There was an association between pre EMD/MDI and changes in EOMs after retrobulbar injection of GCs in GO patients. In patients with predominantly enlarged medial rectus muscles and severe degrees of enlargement, retrobulbar injection of GCs should be assessed for its benefit; a combination of medial and lateral rectus muscle enlargement is beneficial for the shrinkage of EOMs following retrobulbar injections; the involvement of the SRLC rectus muscle may be a disadvantageous pattern of shrinkage of EOMs following retrobulbar injections.Trial registration This study is retrospectively registered. We have registered this study with the Chinese Clinical Trials Registry ( www.chictr.org.cn , registration number: ChiCTR2200063429).

Impact of Hemodialysis on Subfoveal Choroidal Thickness Measured by Optical Coherence Tomography: A Systematic Review and a Pooled Analysis of Self-Controlled Case Series.

INTRODUCTION: Hemodialysis (HD) has various effects on the body, including optimizing body fluid composition and volume, which may have an impact on subfoveal choroidal thickness (SCT) in individuals with end-stage kidney disease (ESKD). However, previous studies have produced conflicting results regarding the effect of HD on SCT in patients with ESKD. Therefore, we conducted a meta-analysis to investigate the influence of HD on SCT. METHODS: A comprehensive search of relevant studies and bibliographies was conducted using Embase, PubMed, and Web of Science databases up to September 2022. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to summarize the SCT change. Heterogeneity and publication bias were assessed, and a random-effects model was employed for the meta-analysis. Subgroup analyses were also performed to evaluate the influence of factors such as diabetes mellitus (DM), the severity of diabetic retinopathy (DR), diurnal variation adjustment, optical coherence tomography (OCT) types, and OCT scan modes. RESULTS: A total of 15 studies involving 1010 eyes were eligible for this meta-analysis, including 552 diabetic eyes, 230 non-diabetic eyes, and the remaining 228 eyes were uncategorized. The meta-analysis revealed a significant reduction in SCT after HD (WMD = -13.66 µm; 95% CI -24.29 to -3.03 µm; z = -5.115, P < 0.0001). Subgroup analysis indicated a significant difference between the DM and non-DM groups (WMD = -24.10 µm vs. -15.37 µm, 95% CI -27.39 to -20.80 µm vs. -19.07 to -11.66 µm; P = 0.001). Additionally, the group with proliferative diabetic retinopathy (PDR) exhibited a more pronounced reduction in SCT (WMD = -28.66 µm; 95% CI -37.10 to -20.23; z = -6.660, P < 0.0001). Adjusting for diurnal variation, different types or scan modes of OCT did not significantly affect the results. CONCLUSION: HD leads to a significant decrease in SCT among patients with ESKD, especially in patients with DM with PDR.

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves' Ophthalmopathy.

Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

Sustained release of tumor cell lysate and CpG from an injectable, cytotoxic hydrogel for melanoma immunotherapy.

Many basic research studies have shown the potential of autologous cancer vaccines in the treatment of melanoma. However, some clinical trials showed that simplex whole tumor cell vaccines can only elicit weak CD8+ T cell-mediated antitumor responses which were not enough for effective tumor elimination. So efficient cancer vaccine delivery strategies with improved immunogenicity are needed. Herein, we described a novel hybrid vaccine "MCL" (Melittin-RADA32-CpG-Lysate) which was composed of melittin, RADA32, CpG and tumor lysate. In this hybrid vaccine, antitumor peptide melittin and self-assembling fusion peptide RADA32 were assembled to form the hydrogel framework melittin-RADA32(MR). Then, whole tumor cell lysate and immune adjuvant CpG-ODN were loaded into MR to develop an injectable and cytotoxic hydrogel MCL. MCL showed excellent ability for sustained drug release, to activate dendritic cells and directly kill melanoma cells in vitro. In vivo, MCL not only exerted direct antitumor activity, but also had robust immune initiation effects including the activation of dendritic cells in draining lymph nodes and the infiltration of cytotoxic T lymphocytes (CTLs) in tumor microenvironment. In addition, MCL can efficiently inhibit melanoma growth in B16-F10 tumor bearing mice, which suggested that MCL is a potential cancer vaccine strategy for melanoma treatment.

TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma.

BACKGROUND: TAP1 is an immunomodulation-related protein that plays different roles in various malignancies. This study investigated the transcriptional expression profile of TAP1 in uveal melanoma (UVM), revealed its potential biological interaction network, and determined its prognostic value. METHODS: CIBERSORT and ESTIMATE bioinformatic methods were used on data sourced from The Cancer Genome Atlas database (TCGA) to determine the correlation between TAP1 expression, UVM prognosis, biological characteristics, and immune infiltration. Gene set enrichment analysis (GSEA) was used to discover the signaling pathways associated with TAP1, while STRING database and CytoHubba were used to construct protein-protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, respectively. An overall survival (OS) prognostic model was constructed to test the predictive efficacy of TAP1, and its effect on the in vitro proliferation activity and metastatic potential of UVM cell line C918 cells was verified by RNA interference. RESULTS: There was a clear association between TAP1 expression and UVM patient prognosis. Upregulated TAP1 was strongly associated with a shorter survival time, higher likelihood of metastasis, and higher mortality outcomes. According to GSEA analysis, various immunity-related signaling pathways such as primary immunodeficiency were enriched in the presence of elevated TAP1 expression. A PPI network and a ceRNA network were constructed to show the interactions among mRNAs, miRNAs, and lncRNAs. Furthermore, TAP1 expression showed a significant positive correlation with immunoscore, stromal score, CD8+ T cells, and dendritic cells, whereas the correlation with B cells and neutrophils was negative. The Cox regression model and calibration plots confirmed a strong agreement between the estimated OS and actual observed patient values. In vitro silencing of TAP1 expression in C918 cells significantly inhibited cell proliferation and metastasis. CONCLUSIONS: This study is the first to demonstrate that TAP1 expression is positively correlated with clinicopathological factors and poor prognosis in UVM. In vitro experiments also verified that TAP1 is associated with C918 cell proliferation, apoptosis, and metastasis. These results suggest that TAP1 may function as an oncogene, prognostic marker, and importantly, as a novel therapeutic target in patients with UVM.

Clinical analysis of 96 patients with intraorbital foreign bodies: A 10-year retrospective study.

Introduction: To investigate the clinical manifestations, diagnosis, and surgical treatment of intraorbital foreign bodies (IOFBs). Methods: Patients with IOFBs were enrolled from Wuhan Union Hospital between January 2011 and January 2021. Demographic and clinical information was extracted, including gender, age, cause and entrance of the trauma, material, size and quantity of foreign body, visual function, ocular complications, imaging findings, and surgical intervention. The patients were divided into two groups according to the timeline, group A (from January 2011 to December 2015, n = 39) and group B (from January 2016 to January 2021, n = 57). Results: The 96 patients (81 men and 15 women) were enrolled in this series, with a median age of 39.5 (1.6-76.0) years. Work-related injuries were the cause of IOFBs in 45 individuals (46.9%). Three patients (3.3%) presented severe visual impairment, and 39 patients (42.4%) presented blindness. The majority of foreign bodies were metal (44.8%), followed by wood (26.0%). Computed tomography (CT) and magnetic resonance imaging (MRI) were performed, respectively, on 89 (92.7%) and 21 (21.9%) patients with IOFBs, in which the detection rate was 80.9% for CT and 81.0% for MRI. Among the 25 patients with intraorbital wooden foreign bodies (IOWFBs), the utilization and detection rates of MRI were 50.0% and 40.0% in group A, and 93.3% and 92.9% in group B, with significant differences in both rates between the two groups (both P < 0.05). The IOWFBs detection rate in MRI was significantly higher than that in CT (78.9% vs. 45.8% overall and 92.9% vs. 53.5% in group B). The detection rates of IOFBs and IOWFBs in initial surgery were statistically different between the two groups, of which the rates were 84.6% and 40.0% in group A and 98.2% and 93.3% in group B. The reoperation rate of IOWFBs in group B (20.0%) was significantly lower than that in group A (70.0%). Conclusion: IOFBs were mainly caused by work-related injuries and might lead to serious visual impairment. The application and detectability of MRI in IOWFBs improved in recent years, and MRI presented better detectability than CT in diagnosing IOWFBs. Thus, MRI should be recommended despite negative CT findings.

MSRAformer: Multiscale spatial reverse attention network for polyp segmentation.

Colon polyp is an important reference basis in the diagnosis of colorectal cancer(CRC). In routine diagnosis, the polyp area is segmented from the colorectal enteroscopy image, and the obtained pathological information is used to assist in the diagnosis of the disease and surgery. It is always a challenging task for accurate segmentation of polyps in colonoscopy images. There are great differences in shape, size, color and texture of the same type of polyps, and it is difficult to distinguish the polyp region from the mucosal boundary. In recent years, convolutional neural network(CNN) has achieved some results in the task of medical image segmentation. However, CNNs focus on the extraction of local features and be short of the extracting ability of global feature information. This paper presents a Multiscale Spatial Reverse Attention Network called MSRAformer with high performance in medical segmentation, which adopts the Swin Transformer encoder with pyramid structure to extract the features of four different stages, and extracts the multi-scale feature information through the multi-scale channel attention module, which enhances the global feature extraction ability and generalization of the network, and preliminarily aggregates a pre-segmentation result. This paper proposes a spatial reverse attention mechanism module to gradually supplement the edge structure and detail information of the polyp region. Extensive experiments on MSRAformer proved that the segmentation effect on the colonoscopy polyp dataset is better than most state-of-the-art(SOTA) medical image segmentation methods, with better generalization performance. Reference implementation of MSRAformer is available at https://github.com/ChengLong1222/MSRAformer-main.

DMs-MAFM+EfficientNet: a hybrid model for predicting dysthyroid optic neuropathy.

Thyroid-associated ophthalmopathy (TAO) is a very common autoimmune orbital disease. Approximately 4%-8% of TAO patients will deteriorate and develop the most severe dysthyroid optic neuropathy (DON). According to the current data provided by clinical experts, there is still a certain proportion of suspected DON patients who cannot be diagnosed, and the clinical evaluation has low sensitivity and specificity. There is an urgent need for an efficient and accurate method to assist physicians in identifying DON. This study proposes a hybrid deep learning model to accurately identify suspected DON patients using computed tomography (CT). The hybrid model is mainly composed of the double multiscale and multi attention fusion module (DMs-MAFM) and a deep convolutional neural network. The DMs-MAFM is the feature extraction module proposed in this study, and it contains a multiscale feature fusion algorithm and improved channel attention and spatial attention, which can capture the features of tiny objects in the images. Multiscale feature fusion is combined with an attention mechanism to form a multilevel feature extraction module. The multiscale fusion algorithm can aggregate different receptive field features, and then fully obtain the channel and spatial correlation of the feature map through the multiscale channel attention aggregation module and spatial attention module, respectively. According to the experimental results, the hybrid model proposed in this study can accurately identify suspected DON patients, with Accuracy reaching 96%, Specificity reaching 99.5%, Sensitivity reaching 94%, Precision reaching 98.9% and F1-score reaching 96.4%. According to the evaluation by experts, the hybrid model proposed in this study has some enlightening significance for the diagnosis and prediction of clinically suspect DON.

Risk prediction of dysthyroid optic neuropathy based on CT imaging features combined the bony orbit with the soft tissue structures.

Purpose: To analyze computed tomographic (CT) imaging features of patients with dysthyroid optic neuropathy (DON) retrospectively and deduce a more appropriate predictive model. Methods: The CT scans and medical records of 60 patients with clinically proven Graves' ophthalmopathy (GO) with (26 women and 10 men) and without DON (16 women and 8 men) were retrospectively reviewed, and 20 age- and sex-matched control participants (12 women and 8 men) were enrolled consecutively. The bony orbit [orbital rim angle (ORA), medial and lateral orbital wall angles (MWA and LWA), orbital apex angle (OAA), and length of the lateral orbital wall (LWL)], and the soft tissue structures [maximum extraocular muscle diameters (Max EOMD), muscle diameter index (MDI), medial and lateral rectus bulk from inter-zygomatic line (MRIZL and LRIZL), proptosis, intraorbital optic nerve stretching length (IONSL), superior ophthalmic vein diameter (SOVD), apical crowding, and presence of intracranial fat prolapse] were assessed on a clinical workstation. The CT features among groups were compared, and a multivariate logistic regression analysis was performed to evaluate the predictive features of DON. Results: All bony orbital angle indicators, except ORA (p = 0.461), were statistically different among the three groups (all p < 0.05). The values of MWA, LWA, OAA, and LWL were larger in the orbits with the DON group than in the orbits without the DON group (all p < 0.05). The MDI, MRIZL, proptosis, IONSL, and SOVD were statistically significantly different among the three groups (all p < 0.05), in which the orbits with the DON group were significantly higher than the orbits without the DON group and control group. The apical crowding was more severe in the orbits with the DON group than in the orbits without the DON group (p = 0.000). There were no significant differences in the LRIZL and the presence of intracranial fat prolapse (all p > 0.05). The multivariate regression analysis showed that the MWA, MDI, and SOVD were the independent factors predictive of DON. The sensitivity and specificity for the presence of DON by combining these three indicators were 89 and 83%, respectively. Conclusion: Bone and soft tissue CT features are useful in the risk prediction of DON, especially the MWA, MDI, and SOVD were the independent factors predictive of DON.

Chromatic visual evoked potentials identify optic nerve dysfunction in patients with Graves' orbitopathy.

PURPOSE: To explore visual dysfunction in Graves' orbitopathy (GO) objectively by analyzing chromatic visual evoked potentials (cVEP) and evaluate its diagnostic efficiency for dysthyroid optic neuropathy (DON). METHODS: In this cross-sectional study, we analyzed pattern-reversal VEP (pVEP), red-green (R-G) and blue-yellow (B-Y) cVEP in 93 subjects (21 with DON, Group A, 30 with GO, Group B, and 42 healthy controls, Group C) at Wuhan Union Hospital, China. RESULTS: Compared with Group C, the amplitudes of B-Y cVEP were significantly lower in Group B, whereas all amplitudes of cVEP, latencies and amplitudes of pVEP in Group A were significantly impaired. In addition, the pVEP latency at 60 arcmin (60'), pVEP amplitudes and R-G cVEP amplitudes were significantly different between Group A and B. Moreover, 60'cVEP R-G negative-positive (N-P) amplitude was correlated with crowding index (P = 0.001), the average thickness of ganglion cell layer and inner plexiform layer (P = 0.004). Furthermore, combination of 60'cVEP R-G amplitude and 60'pVEP P100 latency had better diagnostic efficiency than each single parameter, with optimal cut-off values of 14.20 µV and 110.65 ms, respectively. CONCLUSION: GO may induce electrophysiological changes. The presence of B-Y cVEP anomalies in moderate to severe GO patients may be an early sign of preclinical DON. A decline in 60'cVEP R-G amplitude is associated with apical crowding and thinner inner intra-retinal layers. The combination of 60'cVEP R-G N-P amplitude and 60'pVEP latency can be a useful diagnostic index for DON.

Optic neuropathy associated with GVHD after bone marrow allogeneic hematopoietic stem cell transplantation for B-Acute lymphoblastic leukemia: case report.

BACKGROUND: Graft-versus-host disease (GVHD) is the most common complication after bone marrow allogeneic hematopoietic stem cell transplantation (allo-HSCT). The incidence of posterior segment complications was significantly lower than that of ocular surface lesions. Up to now, there has been no report about optic neuropathy associated with GVHD. CASE PRESENTATION: A 23-year-old man presented with visual acuity decline after allo-HSCT for B-acute lymphoblastic leukemia (B-ALL). Red rashes were found all over the body simultaneously. Visual field examination revealed central scotomas in both eyes. Visual evoked potential showed prolonged P100 latency and decreased P100 amplitude in both eyes. Other ocular examinations showed no obvious abnormality except for blunt pupillary light reflex. The minimal residual disease test was negative after transplantation, and no obvious abnormalities were found in optic nerve and brain by magnetic resonance imaging (MRI). After the multi-disciplinary consultation, the rashes and optic neuropathy were considered GVHD probably. As for the treatment, methylprednisolone and Ruxolitinib were suggested, supported by adjunctive neurotrophic therapy. Two months later, the rashes gradually subsided. However, the visual acuity was not significantly improved at latest follow-up. CONCLUSIONS: The present case report demonstrated GVHD probably associated with optic neuropathy. Although extremely rare, optic nerve should be considered as a potential target of ocular GVHD, which could expand the dimensions of GVHD.

Case series of photic maculopathy associated with exposure to a plasma flash induced by a femtosecond laser.

BACKGROUND AND OBJECTIVES: Photic maculopathy resulting from laser-induced plasma flash has been rarely reported, and the corresponding mechanism of the injury is still unclear. We present a case series of three patients with bilateral macular injuries produced by exposure to the plasma radiation from femtosecond laser tightly focusing. STUDY DESIGN/MATERIALS AND METHODS: Funduscopic findings were accompanied mainly by optical coherence tomography (OCT) investigation of the macula during the follow-up period. RESULTS: All patients shared similar clinical symptoms soon after the initial injury, including reduced visual acuity and central scotomas. It was acutely characterized by foveolar yellowish faceted lesions upon fundus examination. The main OCT finding in the acute stage was a hyper-reflective area involving all foveolar retinal layers without retinal edema. Repeat OCT evaluation during the latter stages revealed that the retinal changes were reversible, but delineated mild pathology at the outer foveal retina. This retinal structural recovery was accompanied by improvements in visual acuity and central scotomas as well. CONCLUSIONS: Prolonged viewing of a plasma flash induced by a focused femtosecond laser without eye protection may produce persistent damage to the retina. We believe that a photochemical process similar to the mechanism of a solar burn or welder's maculopathy may cause retinal damage in this case series.

PCL scaffold combined with rat tail collagen type I to reduce keratocyte differentiation and prevent corneal stroma fibrosis after injury.

The cornea is one of the major refractive eye components and could be easily injured. An ineffective healing of corneal stromal wound may cause fibrosis and even loss of vision. Therefore, it is pivotal to prevent corneal fibrosis after injury. In this study, a poly (ε-caprolactone) (PCL) microfibrous scaffold infused with rat tail collagen type I was fabricated to obtain a 3D composite material. Physical and biological properties of PCL/collagen scaffold were evaluated, the effect of PCL/collagen scaffold on the proliferation and differentiation of limbal stromal stem cells (LSSCs) were detected in vitro, the differentiation of keratocytes as well as the expression and arrangement of extracellular matrix (ECM) influenced by PCL/collagen scaffold were investigated in vivo. RNA-sequencing on normal and injured corneas was carried out to find out the differential enriched pathways and gene expression. We discovered that the PCL/collagen scaffold simulated the stromal structure with properties that were most similar to the native cornea, the PCL/collagen scaffold exhibited good mechanical and biological properties. We also observed that the PCL/collagen scaffold reduced keratocyte differentiation. Injured corneas treated with PCL/collagen scaffold exhibited more regular collagen distribution and less fibroblasts and myofibroblasts distribution. By RNA-sequencing, we observed that in injured group, ECM-related pathway was enriched and several ECM-related genes were up-regulated. This study provides evidence that application of PCL/collagen scaffold could be a new therapeutic strategy for corneal injury.

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy.

Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.

Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study.

Purpose: This study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors. Design: Two-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method. Method: Our study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included. Result: In the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30-1.54; P < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05-1.28; P = 0.003) were genetically predicted to be causally associated with an increased risk of DR, while patients with higher hip circumference (HC) had a lower risk of DR (OR, 95% CI = 0.85, 0.76-0.95; P = 0.004). In the analysis of subtypes of DR, the results of BMI and HC were similar to those of DR, whereas cigarettes per day were only related to proliferative DR (PDR) (OR, 95% CI = 1.18, 1.04-1.33; P = 0.009). In the MR-PRESSO analysis, a higher waist-to-hip ratio (WHR) was a risk factor for DR and PDR (OR, 95% CI = 1.24, 1.02-1.50, P = 0.041; OR, 95% CI = 1.32, 1.01-1.73, P = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures. Conclusion: Our findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.

Intraorbital wooden foreign bodies: case series and literature review.

Intraorbital wooden foreign bodies (IOWFBs) constitute a relatively rare ocular trauma, which occupy a special type of intraorbital foreign bodies (IOFBs). Data regarding IOWFBs must be obtained from case reports or small case series due to their rarity. Here, we reported 5 cases of IOWFBs and reviewed the related literatures, which could provide comprehensive information regarding the clinical manifestations, diagnosis, and surgical treatment of IOWFBs. Combined with the published literature, a total of 51 independent cases were counted after we added 5 cases. Among them, the number of male and female patients was 35 and 16 respectively; the mean age was 27.3±18.2 (range 1-66)y. Obviously, the disorder seemed to occur mainly in young and middle-aged people. Because of the diversity in the clinical manifestations and imaging characteristics of IOWFBs, misdiagnosis and missed diagnosis often occur during the initial visit. Delayed diagnosis may lead to a high risk of orbital infection caused by IOWFBs. Surgery is the treatment of choice for most patients; however, the missed diagnosis and residue of foreign bodies after previous surgery cannot be ignored. Therefore, an accurate diagnosis is governed by the detailed trauma history, careful ocular examination, close observation of clinical manifestations, correct imaging diagnosis [e.g., magnetic resonance imaging (MRI) or computerized tomography (CT)], and timely and completely elimination of IOWFBs.

In vivo confocal microscopy assessment of meibomian glands microstructure in patients with Graves' orbitopathy.

BACKGROUND: To evaluate microstructural changes in the meibomian glands (MGs) in patients with active and inactive Graves' orbitopathy (GO), using in vivo confocal microscopy (IVCM), and to investigate the correlations between clinical and confocal findings. METHODS: Forty patients (80 eyes) with GO (34 eyes with active GO, 46 eyes with inactive GO), and 31 age- and sex-matched control participants (62 eyes) were enrolled consecutively. A researcher recorded the clinical activity score (CAS) for each patient. A complete ophthalmic examination was then performed, including external eye, ocular surface and MGs. IVCM of the MGs was performed to determine the MG acinar density (MAD), MG longest and shortest diameters (MALD and MASD), MG orifice area (MOA), MG acinar irregularity (MAI), meibum secretion reflectivity (MSR), acinar wall inhomogeneity (AWI), acinar periglandular interstices inhomogeneity (API), and severity of MG fibrosis (MF). RESULTS: All confocal microscopy assessments of MGs significantly differed among groups (all P = 0.000). Compared to controls, GO groups showed lower MOA (1985.82 ± 1325.30 µm2 in active GO and 2021.59 ± 1367.45 µm2 in inactive GO vs. 3896.63 ± 891.90 µm2 in controls, all P = 0.000) and MAD (87.21 ± 32.69 /mm2 in active GO and 80.72 ± 35.54 /mm2 in inactive GO vs. 114.69 ± 34.90 /mm2 in controls, P = 0.001 and 0.000, respectively); greater MALD (118.11 ± 30.23 µm in active GO and 120.58 ± 27.64 µm in inactive GO vs. 58.68 ± 20.28 µm in controls, all P = 0.000) and MASD (44.77 ± 19.16 µm in active GO and 46.02 ± 20.70 µm in inactive GO vs. 27.80 ± 9.90 µm in controls, all P = 0.000); and higher degrees of MAI, MSR, and MF (all P<0.05). Eyes with active GO had higher degrees of MAI (P = 0.015), AWI (P = 0.000), and API (P = 0.000), while eyes with inactive GO had higher degrees of MSR (P = 0.000) and MF (P = 0.017). In GO groups, AWI and API were positively correlated with CAS (r = 0.640, P = 0.000; r = 0.683, P = 0.000, respectively), and MF was negatively correlated with CAS (r = - 0.228, P = 0.042). CONCLUSIONS: IVCM effectively revealed microstructural changes of MGs in eyes with GO and provided strong in vivo evidence for the roles of obstruction and inflammation in the ocular surface disease process. Furthermore, it revealed discernible patterns of MG abnormalities in eyes with active GO and inactive GO, which are not easily distinguishable by typical clinical examinations.