Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis.

Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects. Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure. Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis.

Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

Endophthalmitis Caused by Nontuberculous Mycobacterium: Clinical Features, Antimicrobial Susceptibilities, and Treatment Outcomes.

PURPOSE: To report the clinical features, antibiotic susceptibilities and treatment outcomes in patients with endophthalmitis caused by nontuberculous mycobacterium. DESIGN: Noncomparative, consecutive case series. METHODS: Retrospective chart review between December 1990 and June 2014. RESULTS: In the 19 study patients, the clinical setting of endophthalmitis included post-cataract surgery (7/19, 36.8%), post-glaucoma implant (6/19, 31.6%), post-intravitreal injection (2/19, 10.5%), endogenous endophthalmitis (2/19, 10.5%), post-pars plana vitrectomy (1/19, 5.3%), and post-scleral buckle exposure (1/19, 5.3%). Chronic recurrent or persisting ocular inflammation was present in 15 of 19 patients (78.9%). The species isolated were Mycobacterium chelonae in 14 patients (73.7%), M fortuitum in 3 patients (15.8%), M triplex in 1 patient (5.3%), and M avium intracellulare in 1 patient (5.3%). Antibiotic susceptibilities to tested isolates were the following: amikacin (14/16; 87.5%) and clarithromycin (12/16, 75.0%). Intravitreal injections of amikacin (0.4 mg/0.1 mL) were given in 14 of 19 patients (73.7%) with an average of 7 injections per patient (range, 1-24 injections). Intraocular lens removal was performed for 6 of 7 patients (85.7%) with post-cataract surgery endophthalmitis. All the patients with glaucoma implant (6/6, 100%) underwent implant removal. At last follow-up, 6 of 19 patients (31.6%) had best-corrected visual acuity of 20/400 or better. CONCLUSION: Endophthalmitis caused by nontuberculous mycobacterium often included chronic recurrent or persistent intraocular inflammation and frequently required removal of ocular device (intraocular lens, glaucoma implant, or scleral buckle). The majority of the isolates were susceptible to amikacin and clarithromycin. Visual outcomes in these patients even after treatment were generally poor.

Vitrectomy using 0.025% povidone-iodine in balanced salt solution plus for the treatment of postoperative endophthalmitis.

PURPOSE: To investigate the bactericidal effect of 0.025% povidone-iodine in Balanced Salt Solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for postoperative endophthalmitis. METHODS: First, an experimental laboratory model using Staphylococcus aureus was used to evaluate the bactericidal effect of PI-BSS PLUS. Next, in a case series of 4 eyes with postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS as irrigation solution was conducted, followed by postoperative intravitreal and intravenous antibiotics. RESULTS: In in vitro study, PI at concentrations of 0.01% and above in BSS PLUS exhibited marked bactericidal effect after 15 seconds of exposure. Bactericidal effect of 0.025% PI-BSS PLUS was maintained at room temperature storage for 15 minutes but was attenuated after 30 minutes. Among 4 eyes that underwent vitrectomy using 0.025% PI-BSS PLUS, coagulase-negative Staphylococcus sp. was isolated in 1 eye at the beginning but not at completion of surgery. In all four eyes, endophthalmitis was resolved with no adverse events. Ocular toxicity was not observed. CONCLUSION: The 0.025% PI-BSS PLUS is bactericidal and nontoxic when used as irrigation solution in vitrectomy. In 4 cases of postoperative endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS followed by postoperative antibiotics resolved endophthalmitis.

Biocompatibility of pooled human immunoglobulin (Gamunex 10%™) with ocular infusion solutions (BSS™ and BSS Plus™): an in vitro evaluation of a potential antitoxin treatment for infectious endophthalmitis.

PURPOSE: Gamunex 10% (Talecris Biotherapeutics, Research Triangle Park, NC), a commercially available preparation of pooled human immunoglobulin G, has been proposed as an antitoxin therapy against bacterial toxins released in infectious endophthalmitis. Its biocompatibility with two commonly used intraocular infusion fluids was evaluated to determine feasibility of its clinical application in endophthalmitis treatment. METHODS: Gamunex 10% was mixed with BSS or BSS Plus (Alcon Laboratories, Fort Worth, TX) such that it constituted a range of 1.25%-50% by volume. Osmolality, pH, optical density, and ionic strength were measured across this range of concentrations. RESULTS: The amount of pH reduction with increasing concentrations of Gamunex 10% was similar for both BSS and BSS Plus. In BSS Plus, solutions containing up to 20% by volume of Gamunex 10% remained at near-physiologic pH (∼7.0 or above). No physiologically significant changes in osmolality or optical density measurements that would be anticipated to have profound physiological effects were observed at any of the measured concentrations, nor was there visual evidence of tubidity/precipitation. A gradual increase in ionic strength was observed with increasing concentrations of Gamunex 10%. CONCLUSIONS: Potentially therapeutic mixtures of Gamunex 10% in 2 commonly used intraocular infusion fluids, BSS and BSS Plus, showed no evidence of bioincompatibility when the solutions were evaluated for changes in osmolality, pH, ionic strength, aggregation, or precipitation.

Acute-onset endophthalmitis after cataract surgery (2000-2004): incidence, clinical settings, and visual acuity outcomes after treatment.

PURPOSE: To report the incidence, clinical settings, and visual acuity outcomes of acute-onset endophthalmitis after cataract surgery. DESIGN: Retrospective, observational case series. METHODS: Annual cataract surgery statistics were determined by review of electronic surgical records. The clinical and microbiologic records were reviewed of all patients with clinically diagnosed endophthalmitis within 6 weeks after cataract surgery at a single university-affiliated hospital between January 2000 and November 2004. main outcome measures: Operative technique, intraoperative complications, and visual acuity. RESULTS: The incidence of acute-onset endophthalmitis after cataract surgery was 0.04% (7/15,920) for cataract surgeries of all methods, 0.05% (6/11,462) for cataract surgery by clear cornea phacoemulsification, and 0.02% (1/4,458) for cataract surgery by methods other than clear cornea phacoemulsification (P = .681, Fisher's exact test). Six of seven (86%) cases occurred in the right eye, and all cases were performed by right-handed surgeons through temporal incisions. Five of seven (71%) patients had relative immune compromise. Four of seven (57%) patients had an intraoperative complication: vitreous loss in three patients and iris prolapse in one patient. Two patients had topical placement of lidocaine 2% gel before povidone-iodine preparation. The visual acuity at final follow up was 20/25 or better in four patients and count fingers or worse in three patients. CONCLUSIONS: The incidence of acute-onset endophthalmitis after temporal clear cornea incision phacoemulsification is low (0.05%). Potential risk factors for endophthalmitis may include intraoperative complications, relative immune compromise, application of lidocaine 2% gel before povidone-iodine preparation, and inferior incision location.

Surgical treatment for a case of postoperative Pseudallescheria boydii endophthalmitis.

Pseudallescheria boydii (P. boydii) is an uncommon ocular pathogen which previously has been identified in only 10 of 905 fungal isolates identified by the Sid Richardson Microbiology Laboratory at the Cullen Eye Institute of Baylor College of Medicine. Furthermore, only one case of postoperative P. boydii endophthalmitis and four cases of endogenous P. boydii endophthalmitis have been reported. Three of the four patients with endogenous endophthalmitis died within 4 weeks of diagnosis. We describe a second case of postoperative endophthalmitis due to this fungus. The infection was successfully eradicated following vitrectomy, corneoscleral resection, and patch graft, in addition to intraocular, topical, and oral antifungal medication. Although in vitro sensitivities are variable, P. boydii is known to be relatively resistant to amphotericin B. This points to the importance of proper cultures and sensitivities when treating cases of suspected fungal endophthalmitis. Unfortunately, the patient's eye became phthisical 6 months following the initial intervention.