Terbium-doped zinc oxide constructed dual-light-responsive nitric oxide-releasing platform for bacterial keratitis treatment

Bacterial keratitis(BK)is a principal factor contributing to corneal ulcers and ocular complications,and has become a significant killer of global vision health.Traditional antibiotic therapy has unsatisfactory therapeutic effect due to short residence time and low utilization rate of drug,and the long-term abuse of antibiotics can easily incur the prevalence of drug-resistant bacteria.Furthermore,antibiotics are not effective in addressing the excessive inflammatory response caused by infection.Here,we developed a terbium-doped zinc oxide constructed dual-light-responsive nitric oxide(NO)-releasing nanoparticle(ZT@P@B)and modified it on the surface of contact lenses(CL-ZT@P@B)to boost its bioavailability.In vitro and in vivo experimental results verified that ZT@P@B could simultaneously respond to green light(GL)and 808 nm near-infrared(NIR)without obvious damage to the eyes,releasing reactive oxygen species(ROS)and NO,which could effectively kill bacteria(including drug-resistant strains)and reduce inflammatory response.The platform provides a promising strategy for the prevention and treatment of BK.

All-small-molecule supramolecular hydrogels assembled from guanosine 5′-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis

Bacterial keratitis is the most common corneal infection which may lead to blindness,and seriously threatened the human visual health worldwide.Clinical treatment with antibiotic eye drops formulation usually falls in low bioavailability and poor therapeutic efficiency.Hydrogel has gained much attention as ophthalmic formulation recently due to the prolonged drug retention on ocular surface.In this study,we proposed a type of all-small-molecule supramolecular hydrogel assembled from guanosine-5′-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis.Guanosine-5′-monophosphate disodium salt assembled into guanosine-quartet nanofibers via hydrogen bonding andπ-πstacking,and tobramycin with five primary amine groups further crosslinked the nanofibers bearing multiple phosphate moieties into gel networks via ionic interactions.The supramolecular gel showed shear thinning and thixotropic properties,good biocompatibility,and antibacterial activity.The gel treatment significantly ameliorated P.aeruginosa induced bacterial keratitis,and showed higher therapeutic efficacy compared to tobramycin eye drop.This study provides a facile and efficient antibiotic gel formulation for clinical treatment of bacterial keratitis.

Infectious keratitis in Vietnam:etiology,organisms,and management at Vietnam National Eye Hospital

AIM:To report the etiologies,risk factors,treatments,and outcomes of infectious keratitis(IK)at a major Vietnamese eye hospital.METHODS:This is a retrospective review of all cases of IK at Vietnam National Eye Hospital(VNEH)in Hanoi,Vietnam.Medical histories,demographics,clinical features,microbiological results,and treatment outcomes were reviewed.RESULTS:IK was diagnosed in 1974 eyes of 1952 patients,with ocular trauma being the greatest risk factor for IK(34.2%),frequently resulting from an agriculturerelated injur y(53.3%).The mean duration between symptom onset and presentation to VNEH was 19.3±14.4 d,and 98.7%of patients had been treated with topical antibiotic and/or antifungal agents prior to evaluation at VNEH.Based on smear results of 1706 samples,the most common organisms identified were bacteria(n=1107,64.9%)and fungi(n=1092,64.0%),with identification of both bacteria and fungi in 614(36.0%)eyes.Fifty-five of 374 bacterial cultures(14.7%)and 426 of 838 fungal cultures(50.8%)were positive,with the most commonly cultured pathogens being Pseudomonas aeruginosa,Streptococcus pneumonia,Fusarium spp.,and Aspergillus spp.Corneal perforation and descemetocele developed in 391(19.8%)and 93(4.7%)eyes,respectively.Medical treatment was successful in resolving IK in 50.4%eyes,while 337(17.1%)eyes underwent penetrating or anterior lamellar keratoplasty.Evisceration was performed in 7.1%of eyes,most commonly in the setting of fungal keratitis.CONCLUSION:Ocular trauma is a major risk factor for IK in Vietnam,which is diagnosed in almost 400 patients each year at VNEH.Given this,and as approximately one quarter of the eyes that develop IK require corneal transplantation or evisceration,greater emphasis should be placed on the development of prevention and treatment programs for IK in Vietnam.

Changes in interleukin-6 tear concentration and clinical outcome in moderate-to-severe bacterial corneal ulcers after corneal collagen cross-linking

We aimed to evaluate interleukin-6（IL-6） tear concentration and clinical outcome in patients with moderate-to-severe bacterial corneal ulcers post corneal collagen cross-linking（CXL） therapy. This pre-post designed study involving 21 moderate-to-severe corneal ulcer patients who underwent CXL therapy. Patients with infectious corneal ulcer were given CXL therapy as adjunctive treatment after 5 d of broadspectrum antibiotic treatment. Patients with moderate to severe infectious bacterial corneal ulcers were included in this study. Tear sampling was performed before CXL therapy, using sterile Schimer paper from conjunctival inferior fornix. CXL therapy was performed in accordance with the CXL Dresden protocol. Data recording and tear sampling were then performed at day 1 and day 7 after CXL therapy. Data recording included, presence of conjunctival hyperemia, visual analogue scale（VAS）, size of corneal defects, and decemetocele. There was a decrease in IL-6 tear concentration by day 7 after CXL therapy（P=0.001）. IL-6 concentration at 1 h after therapy（2274.67±2120.46 pg/m L） tended to be lower than before therapy（4330.09±3169.70 pg/m L）, but the difference was not statistically significant（P=0.821）. The size of corneal defects decreased significantly post CXL（P=0.007）. The log MAR visual acuity before and after CXL therapy was not found to be significantly different（P=0.277）. There was a significant decrease in VAS values（P=0.018） and blepharospasm（P=0.011） pre and post CXL. There was no significant decrease in conjunctival hyperemia pre and post CXL（P=0.293）. There was significant reduction in IL-6 tear concentration and clinical improvement in moderateto-severe bacterial corneal ulcers which underwent CXL therapy.

Fluorescent silicon nanoparticles-based nanotheranostic agents for rapid diagnosis and treatment of bacteria-induced keratitis

Recommended as a medical emergency,infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness.Herein,we present a kind of theranostic agents,which are made of vancomycin(Van)-modified fluorescent silicon nanoparticles(SiNPs-Van),enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner.Typically,the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro(5 min)and in vivo(10 min),making them an efficacious diagnostic agent for the detection of bacterial keratitis.In addition,the SiNPs-Van feature distinct antimicrobial activity,with superior activity of 92.5%at a concentration of 0.5 ng/mL against Staphylococcus aureus(S.aureus);comparatively,the antimicrobial rate of free vancomycin is 23.3%at the same concentration.We further explore the SiNPs-Van agents as eye drops for therapy of S.aureus-induced bacterial keratitis on rat model.Represented by slit-lamp scores,the keratitis severity of SiNPs-Van-treated corneas is 3.4,which is 59.6%and 77.3%slighter than vancomycin-(8.2 score)and PBS-treated corneas(15.0 score),respectively.The infected corneas recover to normal(1 score)after 7-d of SiNPs-Van treatment.Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents,especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis.