Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor in adults with high mortality rate. Recently, immunotherapy has shown great success in other tumors, however, its therapeutic effect in UM is unsatisfactory, possibly due to the insufficient immune cell infiltration and low immunogenicity of UM. Thus, an efficient therapeutic strategy to reverse the immunosuppressive tumor microenvironment is required. Herein, a PD-L1 modified hierarchical structure consisting of a magnetic Fe3O4 core and spiky silica shell (MNP@Spiky/PD-L1) is developed to reverse the immunosuppressive tumor microenvironment and trigger powerful antitumor immune responses. The MNP@Spiky can induce enhanced immunogenic cell death as well as physical activation of innate immunity. First, tumor cells are disrupted directly by magnetic hyperthermia effect and released tumor-associated antigens to initiate anti-tumor immune responses. Meanwhile, the spiky surface of MNP@Spiky augmented tumor antigen uptake as well as maturation of dendritic cells through inflammasome activation. By further associating with PD-L1-targeting antibody, MNP@Spiky/PD-L1 reversed the immunosuppressive tumor microenvironment and triggered powerful antitumor immune responses. Overall, this synergistic therapeutic strategy effectively reprogramed tumor microenvironment and achieved tumor eradication, which sheds light on clinical UM immunotherapy.

Uveal melanoma (UM) is a highly aggressive ocular malignancy associated with a poor prognosis and significant resistance to conventional therapies, including surgical resection, chemotherapy, and radiotherapy, which are often limited by their efficacy and adverse side effects. Energy-conversion-based nanodynamic therapy, which facilitates the generation of reactive oxygen species (ROS), has emerged as a promising approach for cancer treatment. Here, the development of high-performance multifunctional thermoelectric nanocatalysts, specifically Cu5FeS3.6Se0.4 nanoparticles, optimized for the effective synergistic treatment of UM is reported. These nanoparticles exhibit remarkable photothermal, thermoelectric, and chemodynamic properties that enhance therapeutic efficacy. Under near-infrared light irradiation, Cu5FeS3.6Se0.4 nanoparticles generate localized hyperthermia, which not only induces direct tumor cell ablation but also produces thermoelectric potentials that facilitate ROS generation. Additionally, the hyperthermia induced by the photothermal effects of these nanoparticles accelerates a Fenton-like reaction, leading to the formation of highly reactive hydroxyl radicals for chemodynamic therapy. The resultant ROS induce oxidative stress within tumor cells, promoting mechanisms such as cuproptosis and pyroptosis. The integration of photothermal effects, thermoelectric potentials, and chemodynamic therapy within a single nanoplatform represents an efficient strategy for UM treatment, addressing the shortcomings of traditional therapies and offering a highly effective means of managing this aggressive cancer.

Phototoxicity poses a substantial challenge in photodynamic therapy, resulting in intolerable skin damage, visual impairment, and reduced quality of life. Current coping strategies, primarily focus on avoiding inappropriate photoactivation and developing targeted photosensitizers, have not effectively addressed this problem. Hence, this study aims to develop a "sunlight-friendly" photodynamic therapy strategy. Here, 1-methoxyphenazine methosulfate (MPMS) is innovatively identified as a key substance in achieving modified oxygen metabolism. MPMS demonstrates efficient catalytic shuttling under abnormal intracellular H2O2 levels, introducing a novel protective approach for oxygen metabolism and numerous life processes. By controlling MPMS administration, the switch of the photosensitizer states between "ON" (killing tumor cells) and "OFF" (safeguarding normal cells) can be achieved. This approach effectively mitigated phototoxicity and holds the potential for widespread clinical application.

Introduction Clinically, thyroid-associated ophthalmopathy (TAO) patients were suffered from dry eye syndrome. Only a few relevant studies were about this topic. Our study was determined to provide high-level evidence for the treatment of TAO with dry eye syndrome. Purpose To compare the clinical effects of vitamin A palmitate eye gel and sodium hyaluronate eye drop forTAO patients with dry eye syndrome. Methods The study was conducted in the Ophthalmology Department of the Ninth People’s Hospital Affiliated with the Medical College of Shanghai Jiao Tong University from May to October 2020. A total of 80 mild or moderate-to-severe TAO patients with dry eye syndrome were randomly divided into two groups. The disease stages of all subjects were inactive. Patients in group A were treated with vitamin A palmitate eye gel three times/day for one month and sodium hyaluronate eye drop in group B. The index including break-up time (BUT) and Schirmer I test (ST), corneal fluorescence staining (FL), ocular surface disease index (OSDI), and adverse reactions were recorded by the same clinician at baseline and 1 month after treatment. The data were analyzed by SPSS 24.0. Results Finally, 65 subjects completed the treatment. The average age of the patients in Group A was 38.1 ± 11.4 years, and that in Group B was 37.26 ± 10.67 years. 82% of the subjects in group A were female and 74% in group B. There was no significant difference between the two groups at baseline, including the value of ST, BUT, OSDI, and FL grade. After the treatment, the effective rate was 91.2% in group A, of which the value of BUT and FL grade was significantly improved ( P < 0.001). The effective rate in group B was 67.7%, of which the value of OSDI score and FL grade was significantly improved ( P = 0.002). In addition, the BUT value of group A was significantly longer than that of group B ( P = 0.009). Conclusion InTAO patients with dry eye syndrome, vitamin A palmitate gel and sodium hyaluronate eye drop improved the dry eye and promoted corneal epithelial repair. Vitamin A palmitate gel improves the stability of tear film, while sodium hyaluronate eye drop improves patients’ subjective discomfort.

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) has gradually come into the limelight for oncological treatment due to its noninvasiveness, high specificity, and low side effects. However, upregulated heat-shock proteins (HSPs) and reactive oxygen species (ROS)-defensing system such as glutathione (GSH) or MutT homolog 1 (MTH1) protein in tumor microenvironment counteract the efficiency of single-modality therapy either PTT or PDT. Herein, the well-defined bismuth telluride nanoplates (Bi2 Te3 NPs) are engineered with a high-performance photo-thermo-electro-catalytic effect for tumor-synergistic treatment. Upon near-infrared light illumination, Bi2 Te3 NPs induce a significant temperature elevation for PTT, which effectively inhibits MTH1 expression. Especially, heating and cooling alteration caused temperature variations result in electron-hole separation for ROS generation, which not only damages HSPs to reduce the thermotolerance for enhance PTT, but also arouses tumor cell pyroptosis. Additionally, Bi2 Te3 NPs conspicuously reduce GSH, further improving ROS level and leading to decrease glutathione peroxidase 4 (GPX4) activity, which triggers tumor cell ferroptosis. Due to the photo-thermo-electro-catalytic synergistic therapy, Bi2 Te3 NPs are gifted with impressive tumor suppression on both ectopic and orthotopic ocular tumor models. This work highlights a high-performance multifunctional energy-conversion nanoplatform for reshaping tumor microenvironment to boost the tumor-therapeutic efficacy of phototherapy.

Objective: To report cerebrospinal fluid leak as an uncommon but noteworthy delayed complication after endoscopic orbital surgeries and to describe its incidence, mechanism, prevention, diagnosis, and management. Methods: Case series of 3 patients who underwent endoscopic orbital surgery in the Department of Ophthalmology, Shanghai Ninth People’s Hospital affiliated to Shanghai JiaoTong University School of Medicine from January 2003 to December 2020. A review of the literature was also conducted. Results: Three cases of delayed cerebrospinal fluid leaks occurred 10 years, 3 months, and 4 months after endoscopic orbital surgeries, respectively, were reviewed and reported. Two patients developed cerebrospinal fluid leaks after surgical repair of orbital blowout fractures with titanium mesh and porous polyethylene (Medpor), respectively, and 1 patient developed cerebrospinal fluid leak after transantral optic canal decompression. In the first case, head computed tomography (CT) cisternography and magnetic resonance imaging confirmed the site of the leak that required surgical repair. In the second case, a coronal CT showed that the implanted titanium mesh was tightly against the cribriform plate, which might cause defect of skull base and dura. In the third case, orbital CT identified a dehiscence on the sphenoidal wall as the leak site, which was repaired in a secondary endoscopic surgery. Conclusions: A cerebrospinal fluid leak, as an uncommon but noteworthy complication, can occur as delayed as 10 more years after surgery. For patients with specific anatomic characteristics, such as Kero type III, surgeons should perform meticulous preoperative evaluation and intraoperative procedures to prevent this complication.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor in adults with a high rate of metastasis. Conventional treatments have limited effects on metastasis and cause permanent ocular tissue defects. Here, a novel strategy based on an injectable vitreous substitute with sustained metformin release ability (IVS-Met) was reported for efficient UM therapy as well as for repairing vitreous deficiency and preserving visual function. IVS-Met showed an excellent long-term anti-tumor effect by direct tumor attack and modulation of the tumor microenvironment (TME). IVS-Met reduced the proportion of pro-tumor M2 tumor-associated macrophages and induced the pro-inflammatory M1 phenotype, thus reversing the immunosuppressive TME and eliciting robust anti-tumor immune responses. Notably, IVS-Met demonstrated high performance in the inhibition of UM metastasis and significantly extended the survival time of mice. In addition, the vitreous substitute achieved facile administration via direct injection and exhibited excellent rheological and optical properties with the key parameters very close to those of the vitreous body to repair vitreous deficiency and preserve visual function. In summary, this strategy has realized effective UM treatment while retaining eyeballs and vision for the first time, revealing great potential for translation to clinical practice.

Photobiomodulation using light in the red or near-infrared region is an innovative treatment strategy for a wide range of neurological and psychological conditions. Photobiomodulation can promote neurogenesis and elicit anti-apoptotic, anti-inflammatory and antioxidative responses. Its therapeutic effects have been demonstrated in studies on neurological diseases, peripheral nerve injuries, pain relief and wound healing. We conducted a comprehensive literature review of the application of photobiomodulation in patients with central nervous system diseases in February 2019. The NCBI PubMed database, EMBASE database, Cochrane Library and ScienceDirect database were searched. We reviewed 95 papers and analyzed. Photobiomodulation has wide applicability in the treatment of stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, major depressive disorder, and other diseases. Our analysis provides preliminary evidence that PBM is an effective therapeutic tool for the treatment of central nervous system diseases. However, additional studies with adequate sample size are needed to optimize treatment parameters.

The tumor development and metastasis are closely related to the structure and function of the tumor microenvironment (TME). Recently, TME modulation strategies have attracted much attention in cancer immunotherapy. Despite the preliminary success of immunotherapeutic agents, their therapeutic effects have been restricted by the limited retention time of drugs in TME. Compared with traditional delivery systems, nanoparticles with unique physical properties and elaborate design can efficiently penetrate TME and specifically deliver to the major components in TME. In this review, we briefly introduce the substitutes of TME including dendritic cells, macrophages, fibroblasts, tumor vasculature, tumor-draining lymph nodes and hypoxic state, then review various nanoparticles targeting these components and their applications in tumor therapy. In addition, nanoparticles could be combined with other therapies, including chemotherapy, radiotherapy, and photodynamic therapy, however, the nanoplatform delivery system may not be effective in all types of tumors due to the heterogeneity of different tumors and individuals. The changes of TME at various stages during tumor development are required to be further elucidated so that more individualized nanoplatforms could be designed.

"Where there is a will, there is a way." It is never easy to make progress and development but with full dedication and firm commitment, many aspirations can still be realized. We would like to share with the readers the story of how we develop our division of orbital diseases and surgery from scratch to strengths over a period of 2 decades at the Department of Ophthalmology of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China.

Early warning of tumor formation is crucial for the classification, treatment, and prognosis of tumor patients. Here, a new strategy is reported, aimed at realizing this goal based on imaging aerobic glycolysis processes using nitrogen-doped carbon dots (N-CDs) as fluorescent probes. The intensity of the photoluminescence emitted by the N-CDs is specifically enhanced by nicotinamide adenine dinucleotide (NAD+ , oxidized) in the physiological environment. The N-CDs allow a few (five to ten) abnormal cells in spontaneous hepatocellular carcinoma models to be identified before the in situ development of tumor tissue. The N-CD probes can also distinguish tumor cells from normal cells and be used to evaluate their proliferation activity (with a specificity of up to 96.15% in 13 types of tumor cells and 90.90% in orthotopic xenograft models). The N-CDs are successfully used to monitor the invasion of tumor cells into neighboring tissues and body fluids in 49 clinical samples (with a sensitivity up to 79.31%). These included three vitreous body samples (from patients with retinoblastoma), 42 urine samples (22 patients clinically diagnosed with urothelium carcinoma and 20 healthy persons), and four hydrothorax samples (from patients with metastatic lesions).

Background: Survivors of stroke often experience significant disability and impaired quality of life. The recovery of motor or cognitive function requires long periods. Neuroimaging could measure changes in the brain and monitor recovery process in order to offer timely treatment and assess the effects of therapy. A non-invasive neuroimaging technique near-infrared spectroscopy (NIRS) with its ambulatory, portable, low-cost nature without fixation of subjects has attracted extensive attention. Methods: We conducted a comprehensive literature review in order to review the use of NIRS in stroke or post-stroke patients in July 2018. NCBI Pubmed database, EMBASE database, Cochrane Library and ScienceDirect database were searched. Results: Overall, we reviewed 66 papers. NIRS has a wide range of application, including in monitoring upper limb, lower limb recovery, motor learning, cortical function recovery, cerebral hemodynamic changes, cerebral oxygenation, as well as in therapeutic method, clinical researches, and evaluation of the risk for stroke. Conclusions: This study provides a preliminary evidence of the application of NIRS in stroke patients as a monitoring, therapeutic, and research tool. Further studies could give more emphasize on the combination of NIRS with other techniques and its utility in the prevention of stroke.