Fasting-Mimicking Diet Facilitates Anti-tumor Therapeutic Effects by Nutrient-Sensitive Nanocomposites.

Cancer cells support their uncontrolled proliferation primarily by regulating energy metabolism. Inhibiting tumor growth by blocking the supply of nutrients is an effective treatment strategy. Fasting-mimicking diet (FMD), as a low-calorie, low-protein, low-sugar, high-fat diet, can effectively reduce the nutrient supply to tumor cells. However, the significant biological barrier presented by the tumor microenvironment (TME) imposes greater demands and challenges for drug design, including low efficiency of tumor targeting, increased drug resistance, and limited efficacy of single therapy. In this study, we constructed the multifunctional nanocomposite ZnFe2O4@TiO2@CHC@Orl-FA (ZTCOF), which has great potential to overcome the aforementioned drawbacks. After ZTCOF targeted tumor cells, ZnFe2O4@TiO2 could produce singlet oxygen under the action of ultrasound (US), and stimulate the Fenton-like conversion of endogenous H2O2 to ·OH, achieving the combined killing effect of sonodynamic therapy (SDT) and chemodynamic therapy (CDT) on tumor cells. Starvation treatment with Orl (lipase inhibitor) and CHC (monocarboxylate transporter 1 inhibitor) not only blocked the energy metabolism of tumor cells and inhibited tumor growth but also increased the sensitivity of tumor cells to reactive oxygen species (ROS) and enhanced the killing effect of ROS on tumor cells. At the same time, combining the aforementioned treatment strategies with FMD condition control can further inhibit cancer cell energy metabolism, improve the therapeutic impact of starvation, and achieve significant synergistic anti-tumor therapy. Both in vitro and in vivo experiments confirmed that ZTCOF unified SDT/CDT/starvation therapy into a single nanocomposite, resulting in tumor inhibition and destruction, with optimal therapeutic effect and minimal toxic side effects. This work provides theoretical and technical support for anti-tumor multimodal synergistic therapy. This article is protected by copyright. All rights reserved.

Biofilm microenvironment-activated multimodal therapy nanoplatform for effective anti-bacterial treatment and wound healing.

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3% and 99.6% against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provide a novel approach for developing antibacterial nanomedical platforms.

Ultra-small Janus nanoparticle-induced activation of ferroptosis for synergistic tumor immunotherapy.

Ferroptosis induced by lipid peroxide (LPO) accumulation is an effective cell death pathway for cancer therapy. However, how to effectively induce ferroptosis at tumor sites and improve its therapeutic effectiveness remains challenging. Here, MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex with tumor-specific targeting and TME response is constructed to overcome immunosuppressive tumor microenvironment (TME) to potentiate the curative effect of ferroptosis by coupling the immune checkpoint indoleamine 2,3-dioxygenase (IDO) inhibitor, NLG919, and hyaluronic acid (HA) to novel ultra-small MnFe2O4@NaGdF4 (MG) nanoparticles with a Janus structure. Firstly, tumor site-precise delivery of MG and NLG919 is achieved with HA targeting. Secondly, MG acts as a magnetic resonance imaging contrast agent, which not only has a good photothermal effect to realize tumor photothermal therapy, but also depletes glutathione and catalyzes the production of reactive oxygen species from endogenous H2O2, which effectively promotes the accumulation of LPO and inhibits the expression of glutathione peroxidase 4, achieving enhanced ferroptosis. Thirdly, NLG919 inhibits the differentiation of Tregs by blocking the tryptophan/kynurenine immune escape pathway, thereby reversing immunosuppressive TME together with the Mn2+-activated cGAS-STING pathway. This work contributes new perspectives for the development of novel ultra-small Janus nanoparticles to reshape immunosuppressive TME and ferroptosis activation. STATEMENT OF SIGNIFICANCE: The Janus structured MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex was synthesized, which can realize the precise delivery of T1/T2 contrast agents MnFe2O4@NaGdF4 (MG) and NLG919 at the tumor site under the ultra-small Janus structural characteristics and targeted molecule HA. The production of ROS, consumption of GSH, and photothermal properties of MGNH make it possible for CDT/PTT activated ferroptosis, and synergistically disrupt and reprogram tumor growth and immunosuppressive tumor microenvironment with NLG919 and Mn2+-mediated activation of cGAS-STING pathway, achieving CDT/PTT/immunotherapy activated by ferroptosis. Meanwhile, ultra-small structural properties of MGNH facilitate subsequent metabolic clearance by the body, allowing for the minimization of potential biotoxicity associated with its prolonged retention.

Wet bio-amniotic membrane plugging combined with transplantation in the treatment of small corneal perforations.

PURPOSE: Wet bio-amniotic membrane plugging combined with transplantation is a novel option that combined amniotic membrane plugging with amniotic membrane transplantation for the treatment of small corneal perforations. This study aimed to evaluate the efficacy of wet bio-amniotic membrane plugging in the treatment of small corneal perforations and compared it with that of the penetrating keratoplasty procedure. METHODS: Forty patients (41 eyes) with small corneal perforations <3 mm in diameter treated at our hospital between July 2018 and January 2021 were retrospectively included. Among them, 21 eyes were treated with wet bio-amniotic membrane plugging (wet bio-amniotic membrane plugging group), and 20 eyes were treated with penetrating keratoplasty procedure (penetrating keratoplasty procedure group). The best-corrected visual acuity, anterior chamber formation, corneal thickness, primary disease control, postoperative complications, and graft survival rate were assessed. RESULTS: No significant difference in baseline characteristics was found between the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups (p>0.05). The postoperative control rates of primary diseases in the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups were 95.2% and 90.0%, respectively (p=0.481). Visual acuity was improved 6 months after the operation in the wet bio-amniotic membrane plugging group and was improved at postoperative 1 month in the penetrating keratoplasty procedure group. The formation time of the anterior chamber in the wet bio-amniotic membrane plugging group was significantly shorter than that in the penetrating keratoplasty procedure group (p=0.023). The corneal thickness of the two groups significantly increased 12 months after the operation; however, the degree of thickening in the penetrating keratoplasty procedure group was higher than that in the wet bio-amniotic membrane plugging group (p<0.001). During the follow-up, postoperative complications were not different between the two groups (p>0.999). CONCLUSION: The results suggest that wet bio-amniotic membrane plugging is effective and safe in the treatment of small corneal perforations. Thus, it can be used as an emergency treatment alternative to penetrating keratoplasty procedure for small corneal perforations.

Near-Infrared Light-Triggered Thermoresponsive Pyroptosis System for Synergistic Tumor Immunotherapy.

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light-triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as PCM Pt/GOx) are prepared as the mild-temperature triggered pyroptosis inducer. Pt nanoparticles can not only serve as nanozyme with catalase-like activity to promote GOx catalytic reaction, but also act as photothermal agent to achieve mild-temperature photothermal therapy (PTT) and thermoresponsive GOx release on-demand under the irradiation of NIR light, thereby activating and promoting pyroptosis. In vitro and in vivo experiments prove that NIR light-triggered thermoresponsive pyroptosis system exhibits excellent antitumor immunity activity as well as significantly inhibits tumor growth. The precise control of pyroptosis by NIR light as well as pyroptosis cooperated with mild-temperature PTT for synergistically attenuated tumor immunotherapy are reported for the first time. This work provides a new method to initiate pyroptosis on demand, which is of great significance for spatiotemporally controllable pyroptosis and immunotherapy.

Wet bio-amniotic membrane plugging combined with transplantation in the treatment of small corneal perforations

ABSTRACT Purpose: Wet bio-amniotic membrane plugging combined with transplantation is a novel option that combined amniotic membrane plugging with amniotic membrane transplantation for the treatment of small corneal perforations. This study aimed to evaluate the efficacy of wet bio-amniotic membrane plugging in the treatment of small corneal perforations and compared it with that of the penetrating keratoplasty procedure. Methods: Forty patients (41 eyes) with small corneal perforations <3 mm in diameter treated at our hospital between July 2018 and January 2021 were retrospectively included. Among them, 21 eyes were treated with wet bio-amniotic membrane plugging (wet bio-amniotic membrane plugging group), and 20 eyes were treated with penetrating keratoplasty procedure (penetrating keratoplasty procedure group). The best-corrected visual acuity, anterior chamber formation, corneal thickness, primary disease control, postoperative complications, and graft survival rate were assessed. Results: No significant difference in baseline characteristics was found between the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups (p>0.05). The postoperative control rates of primary diseases in the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups were 95.2% and 90.0%, respectively (p=0.481). Visual acuity was improved 6 months after the operation in the wet bio-amniotic membrane plugging group and was improved at postoperative 1 month in the penetrating keratoplasty procedure group. The formation time of the anterior chamber in the wet bio-amniotic membrane plugging group was significantly shorter than that in the penetrating keratoplasty procedure group (p=0.023). The corneal thickness of the two groups significantly increased 12 months after the operation; however, the degree of thickening in the penetrating keratoplasty procedure group was higher than that in the wet bio-amniotic membrane plugging group (p<0.001). During the follow-up, postoperative complications were not different between the two groups (p>0.999). Conclusion: The results suggest that wet bio-amniotic membrane plugging is effective and safe in the treatment of small corneal perforations. Thus, it can be used as an emergency treatment alternative to penetrating keratoplasty procedure for small corneal perforations.

Tumor Microenvironment-Specific Driven Nanoagents for Synergistic Mitochondria Damage-Related Immunogenic Cell Death and Alleviated Immunosuppression.

Despite significant breakthroughs in immunotherapy, the limitations of inadequate immune stimulation and stubborn immune resistance continue to present opportunities and challenges. Therefore, a two-pronged approach, encompassing the activation of immunogenic cell death (ICD) and blocking the indoleamine 2,3-dioxygenase (IDO)-mediated pathway, is devised to elicit systemic anti-tumor immunity and alleviate immunosuppression. Herein, a tumor microenvironment (TME)-specific driven nanoagent is composed of a tetrasulfide bond-bridged mesoporous silica layer (MON) coated up-conversion nanoparticles as a nano-carrier, combines Fe2+ , curcumin, and indoximod for operating chemodynamic therapy/chemotherapy/immunotherapy. The consumption of glutathione (GSH) caused by MON degradation, the Fenton reaction of Fe2+ , and curcumin triggering mitochondrial damage collectively exacerbate the oxidative stress, leading to a violent immunoreaction and reversal of the immunosuppressive TME through a combination of IDO-inhibitors. Meanwhile, upconversion luminescence (UCL) imaging serves as a significant guiding tool for drug delivery and the treatment of nanoagents. In vivo and in vitro experiment results demonstrate that the nanosystem not only effectively inhibits the growth of primary tumors but also induces immune priming and memory effects to reject re-challenged tumors. The strategy as a complementary approach displays great potential for future immunotherapy along with other multimodal treatment modes.

Rationally Integrated Precise ER-Targeted and Oxygen-Compensated Photodynamic Immunostimulant for Immunogenicity-Boosted Tumor Therapy.

Notwithstanding that immunotherapy has made eminent clinical breakthroughs, activating the immunogenicity and breaking the immunosuppressive tumor microenvironment (ITME) remains tempting yet challenging. Herein, a customized-designed immunostimulant is engineered for attenuating ITME and eliciting an immune response to address this challenge head-on. This immunostimulant is equipped with dual silica layers coated upconversion nanoparticles (UCNPs) as nanocarriers modified with endoplasmic reticulum (ER)-targeted molecular N-p-Tosylglycine, in which the dense silica for chlorin e6 (Ce6) and the glutathione (GSH)-responsive degradable silica for loading resveratrol (RES) - (UCSMRER ). On the one hand, this precise ER-targeted photodynamic therapy (PDT) can generate reactive oxygen species (ROS) in situ under the 980 nm laser irradiation, which not only induced severe cell death directly but also caused intense ER stress-based immunogenic cell death (ICD). On the other hand, tumor hypoxia aggravated by the PDT is alleviated by RES released on-demand, which reduced oxygen consumption by impairing the mitochondrial electron transport chain (ETC). This integrated precise ER-targeted and oxygen-compensated strategy maximized the PDT effect and potentiated ICD-associated immunotherapy, which availed to attenuate ITME, activate tumor immunogenicity, and further magnify the anti-tumor effect. This innovative concept about PDT and immunotherapy sheds light on cancer-related clinical application.

Construction of mPt/ICG-αA nanoparticles with enhanced phototherapeutic activities for multidrug-resistant bacterial eradication and wound healing.

The emergence of multidrug-resistant (MDR) bacterial infections calls for novel strategies for effective bacterial inhibition and wound healing. Phototherapeutic approaches are promising in treating bacterial infection because of their high efficiency, noninvasiveness, and few side effects; however, their antibacterial effect is limited by the formation of biofilms in wounds. Herein, we report novel composite nanoparticles (mPt/ICG-αA NPs) combining mesoporous platinum (mPt) nanoparticles, indocyanine green (ICG) and α-amylase (αA) for combating MDR bacteria and treating wound infection, which integrates a triple bacterial inhibition mechanism arising from the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and α-amylase enzymatic activities. The combination of mPt and ICG significantly enhances the effect of PTT and the temperature can be increased up to 80.8 °C to induce efficacious bacterial degeneration. Meanwhile, mPt/ICG-αA (mPIA) NPs with a low concentration of 25 µg mL-1 exhibited a remarkable catalase activity (CAT) and could continuously decompose endogenous H2O2 into O2 in a hypoxic microenvironment, thereby enhancing the PDT effect to achieve broad-spectrum bactericidal activity. mPIA NPs showed excellent MDR antibacterial efficiency against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and the bactericidal rate reached up to 99.0% and 97.2% with single 808 nm near-infrared light irradiation, respectively. mPIA NPs also exhibited an excellent ability to destroy biofilms and biocompatibility. Animal experiments further suggested that mPIA NPs could achieve the successful repairment of wounds infected with S. aureus in living systems, while this platform demonstrated negligible toxicity towards mice. Considering the superior performances of mPIA NPs, the synergistic αA-CAT-PDT-PTT boosted therapeutic activity presented in the current work provides a promising method to effectively fight against biofilm-related infectious diseases and wound healing.

Novel PdPtCu Nanozymes for Reprogramming Tumor Microenvironment to Boost Immunotherapy Through Endoplasmic Reticulum Stress and Blocking IDO-Mediated Immune Escape.

Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting tumor growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCTER ) is prepared to boost immunotherapy. First, PNBCTER has three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), and peroxidase (POD)-like activities, which can reshape the TME. Second, PNBCTER kills tumor cells by photodynamic therapy (PDT) and photothermal therapy (PTT). Third, guided by TER , PNBCTER not only realizes the combination therapy of PDT, PTT and chemodynamic therapy (CDT), but also damages the ER of tumor cells and actives antitumor immune response, which breaks through the immune blockade of TME. Finally, the NLG919 blocks the tryptophan/kynurenine immune escape pathway and reverses the immunosuppressive TME. The strategy that reshaping the TME by enzyme catalysis and breaking immunosuppression provides a novel way for the application of combination therapy in tumor.

A "Chase and Block" Strategy for Enhanced Cancer Therapy with Hypoxia-Promoted Photodynamic Therapy and Autophagy Inhibition Based on Upconversion Nanocomposites.

The combination of hypoxia-promoted photodynamic therapy (PDT) and autophagy modulation has shown strong potential in the treatment of hypoxic tumors. Here, a novel design is put forward for synergistic PDT and autophagy inhibition to amplify the effect of cancer therapy by a "chase and block" strategy. Specifically, the organic photosensitive molecule (denoted FL) is encapsulated in a hydrophobic layer between multi-band emitted upconversion nanoparticles (UCNPs) and the amphiphilic polymer DSPE-PEG-COOH, allowing FL to fully exploit the luminescence spectrum of UCNPs under near-infrared (NIR) light irradiation. The FL is specifically activated by nitroreductase in the tumor microenvironment (TME), enabling hypoxia-promoted PDT and thus performing a "chase" strategy for cancer therapy. Additionally, the nanosystem is combined with an autophagy-inhibiting melittin pro-peptide (denoted as MEL), which could be triggered by the highly expressed legumain in tumor cells to inhibit the autophagy procedure by disrupting the lysosomal membrane, thus "blocking" the cancer cells from rescuing themselves and amplifying the killing effect of PDT. Both FL and MEL can be specifically activated by TME and the upconversion luminescence imaging of UCNPs offers a tracer function for the treatment. Therefore, UCNPs@FL-MEL might be an important reference for the design and development of future nanotherapeutic agents.

Differential response to topical lubrication in patient with dry eye disease, based on age.

BACKGROUND: To compare the Ocular surface disease index (OSDI) score, Schirmer I test (SIT), fluorescein break up time (FBUT) and fluorescence staining (FLCS) score of dry eye patients at different ages. METHODS: 90 eyes of 90 patients with mild to moderate dry eye from September 2020 to September 2021 were retrospectively included and were divided into young group (20-39 years, n = 29), middle-age group (40-59 years, n = 30), and elder group (> 60 years, n = 31). Patients were given a 28-day topical lubricating ocular surface and repair-promoting drugs combined with local physical therapy. Patients were followed up at 7, 14 and 28 days. The OSDI score, SIT, FBUT and FLCS score were examined. RESULTS: There were differences between the OSDI score in three groups at each time point (all P < 0.001). SIT were different among the three groups (F = 350.61, P < 0.001), and a time effect was found (F = 80.87, P < 0.001). SIT at 14 and 28 days after treatment in middle-age and elder groups were lower than young group (all P < 0.001). SIT at 7, 14 and 28 days in elder group were lower than middle-age group (all P < 0.001). FLCS score was lower at 28 days than other time points (all P < 0.001). CONCLUSION: Dry eye patients are given a 28-day topical lubricating ocular surface and repair-promoting drugs combined with local physical therapy, which can promote tear secretion, film stability, and the recovery of corneal integrity. Age affects the treatment effect of mild to moderate dry eye, among which tear secretion is the most significant.

Characteristics of cathepsin members and expression responses to poly I:C challenge in Pacific cod (Gadus macrocephalus).

Cathepsins are major lysosomal enzymes that participate in necessary physiological processes, including protein degradation, tissue differentiation, and innate or adaptive immune responses. According to their proteolytic activity, vertebrate cathepsins are classified as cysteine proteases (cathepsins B, C, F, H, K, L, O, S, V, W, and X or Z), aspartic proteases (cathepsin D and E), and serine proteases (cathepsin A and G). Several cathepsins were reported in teleosts, however, no cathepsin gene has been identified from Pacific cod so far. In the present study, a total of 13 cathepsin genes were identified for Pacific cod. The evolutionary path of each cathepsin gene was demonstrated via analysis of phylogenetic trees, multiple alignments, conserved domains, motif compositions, and tertiary structures. Tissue distribution analysis showed that all cathepsin genes were ubiquitously expressed in eight healthy tissues but they exhibited diverse levels of expression. Several cathepsin genes were found to be highly expressed in the kidney, spleen, head kidney and liver, whereas low or modest levels were detected in the gills, skin, intestines, and heart. Temporal-specific expression of cathepsins in early developmental stages of Pacific cod were also conducted. CTSK, S, F, and Z were highly expressed at 1 dph and 5 dph and decreased later, while CTSL, L1, and L.1 transcript levels gradually increased in a time-dependent manner. Additionally, the expression profiles of cathepsin genes in Pacific cod were evaluated in the spleen and liver after poly I:C challenge. The results indicated that all cathepsin genes were significantly upregulated upon poly I:C stimulation, suggesting that they play key roles in antiviral immune responses in Pacific cod. Our findings establish a foundation for future exploration of the molecular mechanisms of cathepsins in modulating antiviral immunity in Pacific cod.

lncRNA MEG8 is downregulated in osteoarthritis and regulates chondrocyte cell proliferation, apoptosis and inflammation.

Long noncoding RNA (lncRNA) maternally expressed 8, small nucleolar RNA host gene (MEG8) has been widely reported for its pro-proliferative, anti-apoptotic and anti-inflammatory effects in diverse diseases. The aim of the present study was to investigate the effects and underlying mechanism of MEG8 on IL-1ß-stimulated human osteoarthritis (OA) chondrocytes. C28/I2 chondrocytes were cultured under the stimulation of IL-1ß to establish a cellular model of OA. Functional assays involving Cell Counting Kit-8 and flow cytometry were performed to determine proliferation and apoptosis in the cells. The protein expression levels of caspase-3 and inflammatory cytokines were detected using cell-based ELISA. The expression levels of PI3K/AKT pathway-related proteins were evaluated by western blotting. It was identified that MEG8 expression was increased in the cartilage of patients with OA and in IL-1ß-treated C28/I2 cells. In C28/I2 cells, silencing of MEG8 expression noticeably triggered IL-1ß-induced proliferation suppression, cell death and an inflammatory response. However, transfection with MEG8 displayed adverse effects. Furthermore, MEG8 overexpression prevented IL-1ß-induced activation of the PI3K/AKT signaling pathway in C28/I2 cells. These data demonstrated that MEG8 exerted protective effects against IL-1ß-induced apoptosis and inflammation of OA chondrocytes by regulating the PI3K/AKT signaling pathway. Thus, the present study demonstrates that MEG8 might be a promising target for the treatment of OA.

Efficacy of Lamellar Keratoplasty with Acellular Porcine Corneal Stroma in Treatment for Infectious Central and Peripheral Corneal Ulcers.

BACKGROUND: The aim of this study was to investigate the efficacy of acellular porcine corneal stroma (APCS) transplantation in the treatment of infectious central and peripheral corneal ulcers. METHODS: A total of 45 patients with infectious corneal ulcers who had undergone lamellar keratoplasty using APCS grafts were included. Among these, 24 had lesions located near the pupil (infectious central corneal ulcer group) and 21 had lesions located in the limbus or around the cornea (infectious peripheral corneal ulcer group). Efficacy was assessed in terms of best-corrected visual acuity, graft transparency, corneal neovascularization, corneal reepithelialization, survival rate, and postoperative complications. RESULTS: Baseline characteristics showed that poor visual acuity and larger-diameter APCS graft in the infectious central corneal ulcer group were comparable with the infectious peripheral corneal ulcer grouper group (P<0.05). After lamellar keratoplasty using APCS grafts, no obvious differences were observed in aspects of graft transparency, corneal neovascularization, or survival rate (P>0.05). Postoperative complications, ie, delayed corneal epithelial healing, rejection episode, recurrence of infection, and graft melting, were not significantly different between the two groups (P>0.05). Visual acuity in bothgroups had improved significantly at 3 months and 6 months postoperation, respectively. CONCLUSION: APCS transplantation is safe and efficacious for treating infectious central and peripheral corneal ulcers. Despite its good efficacy, APCS-graft size, implant position, patient indications, and postoperative management should be kept in mind in treatment for infectious corneal ulcers in different locations.

Comparison of modified corneal cross-linking with intrastromal voriconazole for the treatment of fungal corneal ulcer.

The present study aimed to evaluate the efficacy of modified corneal cross-linking (CXL) for the treatment of fungal corneal ulcers compared with that following intrastromal voriconazole injection. In total, 31 patients with fungal corneal ulcers treated at The General Hospital of Northern Theater Command between October 2017 and October 2019 were enrolled. Among them, 10 eyes were treated with ultraviolet A (UV-A)/riboflavin CXL (CXL group), whilst 21 eyes were treated with debridement combined with intrastromal voriconazole (stromal injection group). Preoperative microbiological examination was performed in both groups, and evaluated using Fisher's exact test. Postoperatively, infection control and total efficacy rates, localized lesion, ulcer healing rate 1 week after surgery, visual acuity and complications were evaluated using Fisher's exact test, however visual acuity was analyzed by mixed-model ANOVA. The results showed that the pre-operative species distribution between the CXL and stromal injection groups did not significantly differ. The infection control rate in the CXL group was notably higher compared with that in the stromal injection group (P=0.04). Furthermore, the total efficacy rate in the CXL group was also markedly higher compared with that in the stromal injection group, though no statistically significant differences were observed. Localized lesions were observed in nine eyes (90.0%) in the CXL group and nine eyes (42.9%) in the stromal injection group (P=0.02). However, the rate of ulcer healing at 1 week postoperatively and the logarithm of the minimum angle of resolution (logMAR) of visual acuity were not found to be significantly different between the two groups. In terms of complications, with the exception of one patient in the CXL group exhibiting loss of corneal transparency and one patient in the stromal injection group presenting with partial corneal thinning, no other forms of complications were observed. In conclusion, the present study suggested that CXL could have a beneficial impact for treating fungal corneal ulcers in the aspects of infection control, localized lesions and accelerated epithelialization. In addition, except the loss of corneal transparency, this treatment approach could be applied with reduced risks of adverse events.

The effect of loteprednol suspension eye drops after corneal transplantation.

BACKGROUND: To compare the effect of loteprednol suspension eye drops after corneal transplantation with the effect of prednisolone acetate eye drops. METHODS: A total of 234 patients (234 eyes) who underwent penetrating keratoplasty (PKP) and lamellar keratoplasty (LKP) were retrospectively included. Patients who received 1 % prednisolone acetate eye drops were defined as 1 % prednisolone acetate eye drop group (n = 96), and patients who received 0.5 % loteprednol suspension eye drops were defined as 0.5 % loteprednol suspension eye drop group (n = 138). RESULTS: 35 cases in 1 % prednisolone acetate eye drops group and 27 cases in 0.5 % loteprednol suspension eye drops group developed corticosteroid-induced ocular hypertension, and were defined as prednisolone acetate group and loteprednol group. No significant differences were observed in the average intraocular pressure (IOP) at 1 week, 1 month, 3 months or 12 months postoperatively. There were significant differences in the average IOP between the two groups at 6 months postoperatively (P = 0.001). There were no significant differences in the average best corrected visual acuity (BCVA) at 1, 3 and 12 months postoperatively between two groups. The average 6-month postoperative BCVA was significantly higher in the prednisolone acetate group than the loteprednol group (P < 0.05). There were no significant differences in the postoperative graft rejection rates between the two groups (P > 0.05). CONCLUSIONS: 0.5 % loteprednol suspension eye drops may be considered for long-term use after corneal transplantation.

Comparative Study on the Efficacy of Frozen Amniotic Membrane Transplantation and Lamellar Keratoplasty in the Treatment of Mooren Ulcer.

OBJECTIVE: To compare of the clinical efficacy of frozen amniotic membrane transplantation (AMT) and lamellar keratoplasty (LKP) in the treatment of Mooren ulcer. METHOD: Forty patients (42 eyes) with Mooren's ulcer in our hospital from January 2010 to January 2019 were divided into frozen AMT group (20 eyes) and LKP group (22 eyes). Comparative observation of post-operative best corrected visual acuity (BCVA), corneal epithelial healing time, corneal epithelialization time, ulcer healing, corneal transparency, corneal graft transparency, neovascularization and original disease recurrence were observed. RESULTS: The average BCVA at post-operative 6 and 12 months in LKP group were significantly lower than AMT group (P < 0.05). The ulcer healing rates in LKP group (63.6) were significantly higher than AMT group (30) (P < 0.05). The corneal epithelialization time of LKP group were 9.55 ±â€Š1.26 days. The corneal epithelial healing time of AMT group were 13.50 ±â€Š2.21 days. Nine cases were corneal graft transparency grade 0, and 13 cases were grade I. Three eyes in AMT group were corneal transparency grade 0, 7 were grade I and 10 were grade II. Corneal neovascularization were observed in 3 eyes in AMT group and 4 eyes in LKP group. The original disease recurrence rates in LKP group (50) were significantly higher than AMT group (20) (P < 0.05). Four cases of primary corneal transplantation failure were observed in LKP group. CONCLUSION: Lamellar keratoplasty group obtained significantly better BCVA during follow-up and faster healing time than the frozen AMT group while frozen AMT group had lower original disease recurrence rates than LKP group.

Survey report on keratoplasty in China: A 5-year review from 2014 to 2018.

To provide the general information on corneal transplantation (CT) in China, China Cornea Society designed a questionnaire on CT from 2014 to 2018 and entrusted it to 31 committee members for implementation of the survey nationwide. This article presents the results of the survey and compares the indicators used in the survey and those in the annual statistical report released by the Eye Bank Association of America (EBAA). The number of corneal transplantations completed by the 64 hospitals from 2014 to 2018 was respectively 5377, 6394, 7595, 8270 and 8980, totally 36,616 (22,959 male and 13,657 female). The five largest hospitals by the number of corneal transplantations completed 15,994 surgeries in total, accounting for 43.68% of all the surgeries performed in the 64 hospitals. The most common indication for corneal transplantations was corneal leukoma (7683, 20.98%), followed by bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%) and corneal perforation (2839, 7.75%). The main surgical techniques were penetrating keratoplasty (PK) (19,896, 54.34%), anterior lamellar keratoplasty (ALK) (13,869, 37.88%). The proportion of PK decreased from 57.97% in 2014 to 52.88% in 2018 while the proportion of ALK increased from 36.04% in 2014 to 37.92% in 2018. The geographical distribution of keratoplasties performed in China is unbalanced. PK and ALK were the main techniques of CT and corneal leukoma, bacterial keratitis and corneal dystrophies were the main indications for CT in China.

Comparative observation of the efficacy of simplified Descemet stripping endothelial keratoplasty and penetrating keratoplasty in treating bullous keratopathy.

The aim of the present study was to compare the clinical efficacy between simplified Descemet stripping endothelial keratoplasty (DSEK) and penetrating keratoplasty (PKP) in the treatment of patients with bullous keratopathy (BK). A cohort of 65 patients (65 eyes) with BK recruited between December 2002 and June 2018 was divided into two groups according to the treatment they received: The simplified DSEK group (n=38) and the PKP group (n=27). The best-corrected visual acuity (BCVA) during the follow-up at 1, 3, 6 and 12 months and postoperative complications were all recorded. Furthermore, the graft survival rate after 1 year was recorded. The mean BCVA in the simplified DSEK group was significantly better than that in the PKP group after 1, 3, 6 and 12 months (P<0.05). Furthermore, the 1-year graft survival rate in the simplified DSEK group (91.2%) was significantly higher than that in the PKP group (70.4%; P=0.039). A total of 13 eyes (34.21%) in the simplified DSEK group and 11 eyes (40.74%) in the PKP group were diagnosed with glaucoma; there was no significant difference between the rate of glaucoma diagnosis between the two groups (P=0.591). Graft rejection was observed in 5 eyes (13.16%) of the simplified DSEK group and 8 eyes (29.63%) of the PKP group and the rate of graft rejection did not differ significantly between the groups (P=0.279). Graft infection occurred in 1 eye (2.63%) in the simplified DSEK group and 6 eyes (22.22%) in the PKP group. Simplified DSEK achieved better visual acuity and longer graft survival rates than PKP. The incidence of postoperative secondary glaucoma, graft rejection and graft infection after simplified DSEK was lower than that in the PKP group, but only the incidence of graft infection was significantly different.