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Objective: This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. Methods: This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. Results: In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. Conclusions: A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON.

Gram-negative bacteria can naturally produce nanosized spherical outer membrane vesicles (OMVs) with a lipid bilayer membrane, possessing immunostimulatory capabilities to be potentially applied in tumor therapy. However, the systemic toxicity induced by pathogen-associated molecular patterns (PAMPs) of OMVs is the main obstacle for their clinical translation. Herein, melanin-loaded OMVs were produced with a genetic engineering strategy and further coated with calcium phosphate (CaP) to reduce their toxicity to enhance tumor treatment effects. Wild-type bacterium Escherichia coliNissle 1917 (EcN) was genetically engineered to highly express tyrosinase to catalyze the intracellular synthesis of melanin, giving melanin-loaded OMVs (OMVMel). To reduce the systemic toxicity in tumor therapy, OMVMelwas coated with CaP by surface mineralization to obtain OMVMel@CaP. In comparison with OMVMel, OMVMel@CaP showed lower systemic inflammatory responses in healthy mice and less damage to the liver, spleen, lung, and kidney, so the administration dose could be increased to enhance the antitumor effect. In the acidic tumor microenvironment, the CaP shell disintegrated to release OMVMelto trigger antitumor immune responses. Under costimulation of OMVMelacting as immunoadjuvants and the damage-associated molecular patterns (DAMPs) released by the photothermal effect, the efficiency of tumor photothermal/immunotherapy was largely boosted through promoting the infiltration of matured DCs, M1 macrophages, and activated CD8+T cells, decreasing the ratio of MDSCs in tumors.

Bacteria-based cancer therapy (BCT) has been extensively investigated because of the tumor targeting and antitumor immunity activating abilities of bacteria over traditional nanodrugs, but their potential systemic toxicity poses a challenge. Therefore, it is important to visualize the precise localization and real-time distribution of bacteria in vivoto guide the treatment. Herein, biogenetically engineered Escherichia coliNissle 1917 (EcN) were constructed to highly express tyrosinase to intracellularly generate cyanine 5-labeled melanin-like polymers (Cy5-Mel), thus endowing them with a bright fluorescence and an excellent photothermal performance upon NIR laser irradiation, thereby inducing the intense immunogenic death of tumor cells and release of tumor-associated antigens. Acting as adjuvants, bacteria can greatly stimulate the maturation of dendritic (DC) cells. The in vivobehaviors of these bacteria was monitored vianoninvasive optical imaging when they were intravenously administrated to tumor-bearing mice. From this, NIR exposure on tumor sites was carried out at an appropriate time point to induce the damage to tumor cells and for the modulation of tumor immune microenvironments. Thus, viaa simple bioengineering strategy, a promising bacteria-based theranostic platform was constructed for tumor treatment.

Objective: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder involving the orbital tissue. This study aimed to understand the role of regulatory T cells (Tregs) in TAO during 12-week systemic glucocorticoid (GC) treatment. Methods: Thirty-two moderate-severe TAO patients with a clinical activity score (CAS) ≥3/7 or with prolonged T2 relaxation time (T2RT) on at least one side of extraocular muscle (EOM) were enrolled. The percentage of the peripheral CD4+CD25(high)CD127(−/low) Tregs was analyzed using flow cytometry before and after the GC treatment. The activity and severity of TAO, T2RT, and the clinical outcomes after the GC treatment were assessed. Their correlation with the peripheral Tregs was investigated. Results: There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response. A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement. Conclusion: Treg reduction after systemic GC therapy is indicative of a poor therapeutic response. Accordingly, dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.

Lacrimal canaliculitis (LC) is a rare infection of lacrimal passage, which is usually late diagnosed or misdiagnosed. Traditional lacrimal system tests barely provide a clear and definite understanding of the pathological changes in lacrimal passage. We presented three patients with asymptomatic and atypical symptoms who were misdiagnosed and were eventually diagnosed with chronic LC with assistance of 80‐MHz ultrasound biomicroscopy (80‐MHz UBM) and lacrimal endoscopy. To our knowledge, the mutual assistance of above two techniques diagnosing LC has never been reported, it can provide better images and observations of the canaliculus from the inside out and can guide the differential diagnosis.

Objective: To determine the diagnostic ability of isolated-check visual evoked potential (icVEP), pattern visual evoked potential (pVEP), and standard automated perimetry (SAP) between dysthyroid optic neuropathy (DON) and thyroid-associated ophthalmopathy (TAO) without DON (non-DON). Methods: This is a case-control study, 49 bilateral patients (26 DON and 23 non-DON) were included. icVEP, pVEP, and SAP were conducted in all the subjects, icVEP parameters compared were signal-to-noise ratios (SNRs) under 8, 16, and 32% depth of modulation (DOM). pVEP parameters compared were amplitude and latency. SAP parameters were mean deviation (MD) and pattern standard deviation (PSD). The area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), and decision curve analysis (DCA) were applied for analysis. Results: In icVEP, values of SNR in DON were significantly smaller than non-DON (p< 0.05). In pVEP, P100 latent time in DON was significantly larger than non-DON (p= 0.0026). In SAP, value of PSD in DON was larger than non-DON (p= 0.0006), and value of MD in DON was smaller (p= 0.0007). AUC, NRI, and IDI among the three tests were not significantly different. DCA showed that SNR of icVEP under 8% DOM was the farthest from the two extreme curves. Conclusions: icVEP, pVEP, and SAP have equal diagnostic capabilities to discern between DON and non-DON. In addition, icVEP may represent a significant ancillary diagnostic approach to DON detection, with more clinical benefit.

Background: With the extensive development of endoscopic sinus surgery, iatrogenic medial rectus muscle injury should be treated with caution. Traditional methods to repair a ruptured medial rectus need an anterior orbitotomy approach, with more injury and difficulty in finding the posterior end of the ruptured medial rectus.Objective: To explore a new method to repair a ruptured medial rectus.Methods: Eight cases of iatrogenic medial rectus rupture after endoscopic sinus surgery were reviewed from July 2015 to January 2019. Assisted by image-guided navigation, the ruptured medial rectus was sutured under an endoscopic endonasal orbital approach. Two methods were designed to suture the ruptured medial rectus. Optic nerve and orbital decompression were performed in 5 cases with visual impairment. The extent of exotropia and diplopia were followed up for 5 to 33 months after surgery.Results: With the help of image guidance, the posterior and anterior ends of the ruptured medial rectus of all patients were pinpointed, and operations using medial rectus anastomosis were successfully completed in 7 patients. The exotropia of these patients was corrected, and they have recovered. The vision of 2 patients recovered. There were no minor or major complications intraoperatively or postoperatively.Conclusion: Assisted by image-guided navigation, medial rectus anastomosis under an endoscopic endonasal orbital approach is a feasible method. The key to preventing orbital complications is strict professional training, including identification of the Onodi air cell and correct application of powered instrumentation.

The clinical application of orbital magnetic resonance (MR) T2-mapping imaging in detecting the disease activity of Graves’ ophthalmopathy (GO), and the predictive values of therapy response to intravenous glucocorticoid (ivGC) were investigated. Approved by the local institutional review board (IRB), 106 consecutive patients with GO were included in this prospective study. All subjects were divided into two groups according to the patients’ clinical activity score (CAS): the CAS positive group (CAS ≥3) or the CAS negative group (CAS <3). T2 relaxation time of extraocular muscles (T2RT; ms) and the areas of four extra-ocular muscles (AEOMs; mm2) were measured by 3D T2-mapping MR sequence before and after methylprednisolone treatment, so as the CAS and some ophthalmic examinations including visual acuity, intra-ocular pressure, eyeball movement, diplopia and proptosis. In addition, 24 healthy volunteers were recruited as the control group. The mean T2RT and AEOMs in CAS positive group were higher than those in CAS negative group. Both CAS positive and negative groups had significantly higher mean T2RT and AEOMs than the control group (P<0.01). There was a positive correlation between T2RT and AEOMs values in GO patients, both of them had a positive correlation with CAS and the ophthalmic examinations. It was concluded that to evaluate the activity of GO, CAS was mostly related to inflammation symptoms of ocular surface, more than that, T2RT and AEOMs were also related to abnormal findings of the ophthalmic examinations including high ocular pressure, impaired eyeball movement, diplopia and proptosis. T2RT and AEOMs can reflex the inflammation state of ocular muscles better. CAS combined with 3D T2-mapping MR imaging could improve the sensitivity of detection of active GO so as the prediction and evaluation of the response to methylprednisolone treatment.