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.

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.

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.

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.

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.

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.

Retinal nerve fiber layer thickness measured by optical coherence tomography predicts visual recovery after orbital decompression for dysthyroid optic neuropathy.

PURPOSE: To determine the prognostic value of optical coherence tomography (OCT) measurement of the peripapillary retinal nerve fiber layer (RNFL) thickness in visual recovery after orbital decompression of patients with dysthyroid optic neuropathy (DON). METHODS: A total of 52 eyes of 37 patients who underwent orbital decompression for DON between 2013 and 2019 were retrospectively reviewed. We examined peripapillary RNFL thickness, best-corrected visual acuity (BCVA), visual field (VF) for mean deviation (MD) and pattern standard deviation (PSD), and pattern-reversed visual evoked potential (PVEP) for P100 latency and amplitude before and after surgery. Black and white checkerboard square sizes of PVEP were 15 and 60 arcmin (arcminute and minute of angle). Changes in RNFL overall thickness and by quadrant and interocular differences were evaluated and studied regarding changes in BCVA, VF and PVEP. RESULTS: There was a significant improvement in BCVA, VF, and PVEP, whereas a dramatic reduction in RNFL thickness of all DON patients in global average, temporal, superior, and inferior quadrants (P = 0.005, P = 0.024, P = 0.016, and P = 0.001, respectively) after decompression surgery, except for nasal quadrant (P = 0.057). The preoperative RNFL thickness in each quadrant was negatively correlated with postoperative changes of BCVA and PSD and positively correlated with changes of MD and P100 amplitude at 60 arcmin (all P < 0.05). Except for temporal quadrant (P = 0.125), the preoperative RNFL thickness in other quadrants was positively correlated with postoperative changes of P100 amplitude at 15 arcmin (all P < 0.05). The nasal RNFL thickness was an excellent predictor for improvement in BCVA by 20/25 or better and in MD by 10 dB or more after surgery, whose cutoff value was 73.50 µm, while the inferior and superior RNFL thickness could act as a predictor for improvement in P100 amplitude by 5 µV or more at 60 arcmin and at 15 arcmin, respectively, whose cutoff value was, respectively, 143.00 µm and 130.50 µm (all P < 0.05). CONCLUSION: RNFL thickness measured by OCT was correlated with visual function recovery after decompression surgery in patients with DON, which could also act as a predictor for better visual prognosis.

The Expression of Calcium Sensing Receptor in Normal and Diabetic Rat Eyes.

BACKGROUND Calcium sensing receptor (CaSR) is widely expressed in many tissues of the body, but it is rarely reported to be expressed in the eyes. This research explored the expression and distribution of CaSR in eye tissues of normal and diabetic rats. MATERIAL AND METHODS Thirty male Sprague Dawley (SD) rats were randomly divided into a diabetic and a normal group. Diabetes mellitus (DM) models were successfully established by intraperitoneal injection of streptozotocin. The expression and distribution of CaSR in the rat eyeballs were detected by immunohistochemistry. Quantitative RT-PCR and western blotting were used to detect the presence of CaSR in normal and diabetic rats. RESULTS CaSR was detected in the cornea, lens epithelium, and retina. CaSR was expressed the most in the cornea, followed by the lens epithelium, and the retina (p<0.05). The expression of CaSR was decreased in the eye tissue of diabetic rats (p<0.05). CONCLUSIONS In this study, CaSR was detected in rat cornea, lens, and retina. It was significantly decreased in the eyes of diabetic rats. This indicated that the downregulated expression of CaSR was associated with diabetic oculopathy.

Whole exome sequencing identifies a novel NRL mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

PURPOSE: To investigate the genetic basis and its relationship to the clinical manifestations in a four generation Chinese family with autosomal dominant retinitis pigmentosa. METHODS: Ophthalmologic examinations including fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, optical coherence tomography, and a best-corrected visual acuity test were performed to define the clinical features of the patients. We extracted the genomic DNA from peripheral blood samples. The proband's genomic DNA was submitted to the whole exome sequencing. RESULTS: Whole exome sequencing and the subsequent data analysis detected six candidate mutations in the proband of this pedigree. The novel c.146 C>T mutation in NRL was found to be the only mutation that co-segregated with the disease in this pedigree. This mutation resulted in a substitution of proline by a leucine at position 49 of NRL protein (p.P49L). Most importantly, the proline residue at position 49 of NRL is highly conserved from zebrafish to humans. The c.146 C>T mutation was not observed in 200 control individuals. What's more, we performed the luciferase activity assay to prove that this mutation we detected alters the NRL protein function. CONCLUSIONS: The c.146 C>T mutation in NRL gene causes autosomal dominant retinitis pigmentosa for this family. Our finding not only expands the mutation spectrum of NRL, but also demonstrates that whole-exome sequencing is a powerful strategy to detect causative genes and mutations in RP patients. This technique may provide a precise diagnosis for rare heterogeneous monogenic disorders such as RP.

Sclerectomy with nanojoule energy level per pulse by femtosecond fiber laser in vitro.

The use of nanojoule femtosecond pulses (NFP) for highly precise proceeding in anti-glaucoma surgery was evaluated. According to the observation of scanning electron microscopy (SEM), four types of incision patterns, including subsurface, slit-like, spot and cuboid ablations, were accomplished on in vitro sclera by NFP with little collateral damage. In comparison to microjoule femtosecond pulses (MFP), NFP can make extremely precise incisions with smoother inner surface with less peak power density. The present study first illustrates the potential use of NFP in minimally invasive laser sclerectomy for glaucoma therapy.

Toll-like receptor 4 in bone marrow-derived cells contributes to the progression of diabetic retinopathy.

Diabetic retinopathy (DR) is a major microvascular complication in diabetics, and its mechanism is not fully understood. Toll-like receptor 4 (TLR4) plays a pivotal role in the maintenance of the inflammatory state during DR, and the deletion of TLR4 eventually alleviates the diabetic inflammatory state. To further elucidate the mechanism of DR, we used bone marrow transplantation to establish reciprocal chimeric animals of TLR4 mutant mice and TLR4 WT mice combined with diabetes mellitus (DM) induction by streptozotocin (STZ) treatment to identify the role of TLR4 in different cell types in the development of the proinflammatory state during DR. TLR4 mutation did not block the occurrence of high blood glucose after STZ injection compared with WT mice but did alleviate the progression of DR and alter the expression of the small vessel proliferation-related genes, vascular endothelial growth factor (VEGF), and hypoxia inducible factor-1α (HIF-1α). Grafting bone marrow-derived cells from TLR4 WT mice into TLR4 mutant mice increased the levels of TNF-α, IL-1ß, and MIP-2 and increased the damage to the retina. Similarly, VEGF and HIF-1α expression were restored by the bone marrow transplantation. These findings identify an essential role for TLR4 in bone marrow-derived cells contributing to the progression of DR.

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.

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.

Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1.

PURPOSE: To identify the disease-causing mutation(s) in a Chinese family with autosomal recessive Usher syndrome type 1 (USH1). METHODS: An ophthalmic examination and an audiometric test were conducted to ascertain the phenotype of two affected siblings. The microsatellite marker D11S937, which is close to the candidate gene MYO7A (USH1B locus), was selected for genotyping. From the DNA of the proband, all coding exons and exon-intron boundaries of MYO7A were sequenced to identify the disease-causing mutation(s). Restriction fragment length polymorphism (RFLP) analysis was performed to exclude the alternative conclusion that the mutations are non-pathogenic rare polymorphisms. RESULTS: Based on severe hearing impairment, unintelligible speech, and retinitis pigmentosa, a clinical diagnosis of Usher syndrome type 1 was made. The genotyping results did not exclude the USH1B locus, which suggested that the MYO7A gene was likely the gene associated with the disease-causing mutation(s) in the family. With direct DNA sequencing of MYO7A, two novel compound heterozygous mutations (c.3742G>A and c.6051+1G>A) of MYO7A were identified in the proband. DNA sequence analysis and RFLP analysis of other family members showed that the mutations cosegregated with the disease. Unaffected members, including the parents, uncle, and sister of the proband, carry only one of the two mutations. The mutations were not present in the controls (100 normal Chinese subjects=200 chromosomes) according to the RFLP analysis. CONCLUSIONS: In this study, we identified two novel mutations, c.3742G>A (p.E1248K) and c.6051+1G>A (donor splice site mutation in intron 44), of MYO7A in a Chinese non-consanguineous family with USH1. The mutations cosegregated with the disease and most likely cause the phenotype in the two affected siblings who carry these mutations compound heterozygously. Our finding expands the mutational spectrum of MYO7A.

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.

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).

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.

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.