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Funder: Science and Technology Planning Projects of Guangdong Province (2018B010109008);Guangzhou Key Laboratory Project (202002010006);Hainan Province Clinical Medical Center, Funder: Fight for Sight (UK), the Isaac Newton Trust (UK), Moorfields Eye Charity (GR001376), the Addenbrooke’s Charitable Trust, the National Eye Research Centre (UK), the International Foundation for Optic Nerve Disease (IFOND), the NIHR as part of the Rare Diseases Translational Research Collaboration, the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), and the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, Funder: the National Key R&D Program of China (2018YFA0704000);Beijing Natural Science Foundation (JQ19015), Funder: the Institute for Brain and Cognitive Science, Tsinghua University (THUIBCS);Beijing Laboratory of Brain and Cognitive Intelligence, Beijing Municipal Education Commission (BLBCI), The storage of facial images in medical records poses privacy risks due to the sensitive nature of the personal biometric information that can be extracted from such images. To minimize these risks, we developed a new technology, called the digital mask (DM), which is based on three-dimensional reconstruction and deep-learning algorithms to irreversibly erase identifiable features, while retaining disease-relevant features needed for diagnosis. In a prospective clinical study to evaluate the technology for diagnosis of ocular conditions, we found very high diagnostic consistency between the use of original and reconstructed facial videos (κ ≥ 0.845 for strabismus, ptosis and nystagmus, and κ = 0.801 for thyroid-associated orbitopathy) and comparable diagnostic accuracy (P ≥ 0.131 for all ocular conditions tested) was observed. Identity removal validation using multiple-choice questions showed that compared to image cropping, the DM could much more effectively remove identity attributes from facial images. We further confirmed the ability of the DM to evade recognition systems using artificial intelligence-powered re-identification algorithms. Moreover, use of the DM increased the willingness of patients with ocular conditions to provide their facial images as health information during medical treatment. These results indicate the potential of the DM algorithm to protect the privacy of patients' facial images in an era of rapid adoption of digital health technologies.

Fibrosis is the late stage of thyroid-associated ophthalmopathy (TAO), resulting in serious complications. Effective therapeutic drugs are still lacking. We aimed to explore the mechanism of TAO fibrosis and to find a targeted drug. High-throughput RNA sequencing was performed on orbital connective tissues from twelve patients with TAO and six healthy controls. Protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and we identified the hub gene by Cytoscape software. Additionally, the RNA sequencing results were validated by quantitative real-time polymerase chain reaction (qRT–PCR). Bioinformatic prediction identified the functions of differentially expressed genes (DEGs). Further orbital connective tissue and serum samples of the TAO and control groups were collected for subsequent experiments. Histologic staining, Western blotting (WB), qRT–PCR, enzyme-linked immunosorbent assays (ELISAs), gene overexpression through lentiviral infection or silencing gene by short interfering RNA (siRNA) were performed. We found that the relaxin signaling pathway is an important regulatory pathway in TAO fibrosis pathogenesis. Serelaxin exerts antifibrotic and anti-inflammatory effects in TAO. Furthermore, the downstream Notch pathway was activated by serelaxin and was essential to the antifibrotic effect of serelaxin in TAO. The antifibrotic effect of serelaxin is dependent on RXFP1.

Purpose To improve public and medical awareness of the possibility of retinoblastoma (RB) in children who experienced inadvertent trauma with or without trauma-related symptoms and signs. Patients and methods Retrospective study of the clinical characteristics of children with a trauma history preceding a diagnosis of RB at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 2013 and August 2018, and the number of children hospitalized with eye trauma during the same period. Results Among 793 consecutive patients with RB, 10 (1.3%) had a history of trauma. Two of these 10 patients (20%, accounting for nearly 0.2% of the 1103 eye trauma patients who were treated at our center) had undergone vitrectomy in an eye with unsuspected tumors. Of the 10 cases (12 eyes), only 5 (7 eyes) were initially diagnosed with RB or an intraocular space-occupying mass before referral to the oncology clinic, and 8 patients (80%) with 8 eyes that were ultimately staged as cT2b or higher underwent enucleation on referral to the oncology clinic. Although additional treatment was performed, two of these patients experienced intracranial metastasis and death during a mean follow-up time of 25.9 months from treatment. Conclusion More attention should be paid to the possibility of underlying RB in children of preschool age who have experienced trauma with or without eye signs.

Purpose To investigate the change in IL-10–producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10–producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays. Results Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro. Conclusions Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.

BackgroundIdiopathic orbital inflammation (IOI) is a disfiguring and vision-threatening fibroinflammatory disorder. The pathogenesis of IOI has not been elucidated. We sought to clarify the regulatory T cell (Treg) distribution and function in patients with IOI.MethodsThe frequency, phenotype and function of Tregs were identified by multicolor flow cytometry and in vitro cell functional assays. Plasma and tissue samples were obtained to investigate cytokines, chemokines and their receptors of interest by relative real-time polymerase chain reaction (PCR) and Luminex assays.ResultsCompared with healthy subjects, patients with IOI exhibited obvious increases of Tregs in peripheral blood and affected orbital tissues. Circulating Tregs from patients with IOI were significantly more polarized to a Th17-like phenotype with defective regulatory function, whereas orbit-derived Tregs were polarized to a Th2-like phenotype. Furthermore, ST2 expression levels in circulating Tregs and interleukin (IL)-33 mRNA levels in orbital tissues were decreased in IOI. IL-33 restored the suppressive function of Tregs, reduced interferon (IFN)-γ production by Tregs and decreased the activation of orbital fibroblasts (OFs) cocultured with Tregs in IOI.ConclusionIncreased Tregs with proinflammatory and profibrotic polarization were first identified in IOI, suggesting that Treg plasticity and heterogeneity plays an essential role in IOI pathogenesis. Additionally, our study identified a regulatory effect of IL-33 on inflammation and fibrosis in IOI. Reversing the plastic Tregs via IL-33 might be a potential option for IOI patients.

Background Cavernous hemangioma and schwannoma are tumors that both occur in the orbit. Because the treatment strategies of these two tumors are different, it is necessary to distinguish them at treatment initiation. Magnetic resonance imaging (MRI) is typically used to differentiate these two tumor types; however, they present similar features in MRI images which increases the difficulty of differential diagnosis. This study aims to devise and develop an artificial intelligence framework to improve the accuracy of clinicians' diagnoses and enable more effective treatment decisions by automatically distinguishing cavernous hemangioma from schwannoma. Methods Material: As the study materials, we chose MRI images as the study materials that represented patients from diverse areas in China who had been referred to our center from more than 45 different hospitals. All images were initially acquired on films, which we scanned into digital versions and recut. Finally, 11,489 images of cavernous hemangioma (from 33 different hospitals) and 3,478 images of schwannoma (from 16 different hospitals) were collected. Labeling: All images were labeled using standard anatomical knowledge and pathological diagnosis. Training: Three types of models were trained in sequence (a total of 96 models), with each model including a specific improvement. The first two model groups were eye- and tumor-positioning models designed to reduce the identification scope, while the third model group consisted of classification models trained to make the final diagnosis. Results First, internal four-fold cross-validation processes were conducted for all the models. During the validation of the first group, the 32 eye-positioning models were able to localize the position of the eyes with an average precision of 100%. In the second group, the 28 tumor-positioning models were able to reach an average precision above 90%. Subsequently, using the third group, the accuracy of all 32 tumor classification models reached nearly 90%. Next, external validation processes of 32 tumor classification models were conducted. The results showed that the accuracy of the transverse T1-weighted contrast-enhanced sequence reached 91.13%; the accuracy of the remaining models was significantly lower compared with the ground truth. Conclusions The findings of this retrospective study show that an artificial intelligence framework can achieve high accuracy, sensitivity, and specificity in automated differential diagnosis between cavernous hemangioma and schwannoma in a real-world setting, which can help doctors determine appropriate treatments.

Purpose To improve public and medical awareness of the possibility of retinoblastoma (RB) in children who experienced inadvertent trauma with or without trauma-related symptoms and signs. Patients and methods Retrospective study of the clinical characteristics of children with a trauma history preceding a diagnosis of RB at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 2013 and August 2018, and the number of children hospitalized with eye trauma during the same period. Results Among 793 consecutive patients with RB, 10 (1.3%) had a history of trauma. Two of these 10 patients (20%, accounting for nearly 0.2% of the 1103 eye trauma patients who were treated at our center) had undergone vitrectomy in an eye with unsuspected tumors. Of the 10 cases (12 eyes), only 5 (7 eyes) were initially diagnosed with RB or an intraocular space-occupying mass before referral to the oncology clinic, and 8 patients (80%) with 8 eyes that were ultimately staged as cT2b or higher underwent enucleation on referral to the oncology clinic. Although additional treatment was performed, two of these patients experienced intracranial metastasis and death during a mean follow-up time of 25.9 months from treatment. Conclusion More attention should be paid to the possibility of underlying RB in children of preschool age who have experienced trauma with or without eye signs.