OBJECTIVE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The US Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared to monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized.
METHODS: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase 2 Ladder (NCT02510794) and phase 3 Archway (NCT03677934) and Portal (NCT03683251) trials.
METHODS: Endophthalmitis cases in the pooled all-PDS safety population (N = 555) including PDS patients in Ladder, Archway, or Portal.
METHODS: Ladder patients received PDS (10, 40, or 100 mg/mL) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/mL with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day 1.
METHODS: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications.
RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range: 57-853), including 4 before the first refill-exchange (day range: 57-161). Five patients received between 1-11 refill-exchanges before the event (onset: 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥ 20/40; 4 patients experienced vision loss of ≥ 15 ETDRS letters.
CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. This limited series of endophthalmitis cases notes most, but not all, cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes.

Intravitreal injections (IVI s) have gained increased popularity in the past decades and are used to treat a multitude of ailments. In 2010, the total number of IVI s surpassed the number of cataract surgeries performed, making it the most common procedure in ophthalmology. As the number of injections increases, so does the number of injected-related complications. While complications in the posterior segment, such as retinal detachment or endophthalmitis, are detrimental to visual function and have therefore been well documented, IVI s can also lead to complications in the anterior segment. These include hyphema, inflammation of the sterile anterior segment (incidence rate of 0.05 to 1.1% depending on the drug), implant migration with corneal decompensation (incidence rate of 0.43%), iatrogenic lens damage (incidence rate of 0.07%), accelerated cataract formation (up to 50% for steroids and 10.9% for anti-VEGF), and an increased complication rate during subsequent cataract surgery (up to 4% per IVI). Most of these complications occur immediately and have a good prognosis if treated correctly. However, the increased risk of complications during subsequent surgery demonstrates that IVI s can also have long-term complications, a topic that needs to be explored further in future research projects.
Intravitreale Injektionen (IVI) haben in den letzten Jahrzehnten zunehmend an Beliebtheit gewonnen und werden zur Behandlung einer Vielzahl von Erkrankungen eingesetzt. Im Jahr 2010 hat die Gesamtzahl der IVI s die Anzahl der durchgeführten Kataraktoperationen übertroffen, wodurch sie zum häufigsten Verfahren in der Augenheilkunde wurden. Mit der zunehmenden Anzahl von Injektionen steigt auch die Anzahl der damit verbundenen Komplikationen. Während Komplikationen im hinteren Augenabschnitt, wie die Netzhautablösung oder die Endophthalmitis, katastrophal für die Sehfunktion und heute gut dokumentiert sind, können IVI s auch zu Komplikationen im vorderen Augenabschnitt führen. Dazu gehören Hyphäma, sterile Entzündung des vorderen Augenabschnitts (Inzidenzrate: 0,05% – 1,1% je nach Medikament), Implantatmigration mit Hornhautdekompensation (Inzidenzrate: 0,43%), iatrogene Linsenschäden (Inzidenzrate: 0,07%), beschleunigte Kataraktbildung (bis zu 50% für Steroide und 10,9% für Anti-VEGF) und erhöhte Komplikationsrate während späterer Kataraktoperationen (bis zu 4% pro IVI). Die meisten dieser Komplikationen treten sofort auf und haben eine gute Prognose, wenn sie richtig behandelt werden. Die erhöhte Komplikationsrate während späterer Operationen zeigt jedoch, dass IVI s auch langfristige Komplikationen verursachen können, ein Thema, das in späteren Forschungsprojekten weiter erkundet werden sollte.

UNASSIGNED: To determine the physiological status of the retina of eyes with endophthalmitis by examining the electroretinograms (ERGs) recorded with a portable recording system and to determine whether the pretreatment ERG findings were correlated with the best-corrected visual acuity (BCVA) after the treatment.
UNASSIGNED: We examined the medical records of 118 eyes of 108 patients who were diagnosed and treated for infectious endophthalmitis at Saitama Medical University Hospital, Japan, between January 2015 to November 2022. Of these, we studied the 25 eyes of 21 patients who had been evaluated by electroretinography. In bilateral cases, one eye was analyzed. The eyes were classified into those with postoperative endophthalmitis (group S, n = 12) and those with endogenous endophthalmitis (group E, n = 9). Photopic and flicker ERGs were recorded with the RETeval system. The pretreatment clinical factors studied were the ERG components that might be correlated with the post-treatment BCVA.
UNASSIGNED: Eyes in Group E with larger amplitude flicker ERGs (P = 0.0053, ρ = -0.8333) had better BCVA after treatment. In Group S, eyes with larger amplitude flicker ERGs (P = 0.0086, ρ = -0.7173), photopic a-waves (P = 0.0323, ρ = 0.6177), and photopic b-waves (P = 0.0055, ρ = -0.7443) had better BCVA after treatment.
UNASSIGNED: Simple and rapid ERG evaluations under light-adapted condition are helpful in evaluating the pretreatment retinal function and to determine the visual prognosis in eyes with endophthalmitis.
UNASSIGNED: Simple and non-time-consuming ERG evaluations are helpful in evaluating the retinal function in eyes with endophthalmitis and predicting the visual prognosis.

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of large-scale use of vancomycin injection in an infusion bottle during vitreoretinal procedures.
METHODS: This was a retrospective evaluation of all vitreoretinal procedures done in the last 70 months, where intraoperatively vancomycin injection (0.2 mg/mL) was used in an infusion bottle prophylactically as standard care. Vitreoretinal procedures were categorized as major (duration >30 min), minor (duration <30 min), and silicone oil removal. Postoperatively, a detailed ocular examination was done to rule out hemorrhagic occlusive retinal vasculitis (HORV) or signs of postoperative bacterial endophthalmitis.
RESULTS: Over the last 70 months, a total of 31,720 vitreoretinal procedures were performed, which included 24,371 major vitreoretinal procedures, 1401 minor vitreoretinal procedures, and 5948 silicone oil removal cases. None of these cases developed HORV or bacterial endophthalmitis.
CONCLUSIONS: Vancomycin (0.2 mg/mL) in infusion fluid during vitreoretinal procedures is safe and can be advocated as a prophylactic measure against postvitrectomy bacterial infections.

A 76-year-old male presented with pain, redness, and decreased vision in the left eye for 5 days. The patient had undergone combined cataract extraction and vitrectomy for a macular hole 2 weeks back. The vision had reduced to the perception of light in the left eye. Clinical examination revealed lid edema, conjunctival congestion, hazy cornea, and exudative membrane in the pupillary axis with no view of the fundus. Ultrasound examination of the left eye showed plenty of moderate reflective dot echoes. The patient was diagnosed with postoperative endophthalmitis and underwent vitrectomy with intravitreal injection of antibiotics. Growth of Hathewaya histolytica was obtained from the vitreous sample. The organism was sensitive to imipenem. Three weeks following the presentation, visual acuity had improved to counting fingers at one meter in the left eye. This is the first report of endophthalmitis due to H. histolytica. Ophthalmologists should be aware of such ocular infections due to a rare microorganism.

UNASSIGNED: We constructed a clinical clue-based algorithm to identify the microbiology-positive post-cataract surgery endophthalmitis.
UNASSIGNED: The Endophthalmitis Infectivity Measurement Algorithm (EIMA) was constructed using presenting Snellen vision (Letter score [LS]) and Inflammation Score (IS, from the cornea, anterior chamber, iris, and vitreous). Retrospective data (70% for training; 30% for testing) was fitted into CHAID (Chi-squared Automatic Interaction Detection). EIMA was validated with prospective data. EIMA-categorized disease severity was weighed against the symptom duration to detect infecting micro-organisms.
UNASSIGNED: EIMA was constructed from 1444 retrospective data. The average LS was 6.03 ± 12.11, median IS was 14 (8-24), and culture positivity was 38%. The accuracy and area under the curve of CHAID were 66.36% and 0.642, respectively. EIMA was validated with 175 prospectively collected data. Microbiology positivity (culture + sequencing) was 58.9%. EIMA sensitivity, specificity, and accuracy against microbiology-positive endophthalmitis were 73.7 (95% confidence interval [CI], 64.19-81.96), 81.9 (95% CI, 71.1-90.02), 77.1 (95% CI, 70.20-83.14), respectively. The positive and negative likelihood ratios were 4.08 (95% CI, 2.46-6.67) and 0.32 (95% CI, 0.22-0.45), respectively. There was higher microbial growth in two days or less than in three- to six-day symptom duration (69.9% vs. 28.2%; P = 0.018) endophthalmitis. Gram-negative infection was higher in two days or less (55.6% vs. 20.2%; P = 0.014), and gram-positive infection was higher in three- to six-day endophthalmitis (62.1% vs. 27.7%; P = 0.027).
UNASSIGNED: EIMA identified microbiology-positive endophthalmitis three-quarters of the time.
UNASSIGNED: EIMA suggested infectivity and the class of microbial infection could help targeted management of endophthalmitis after cataract surgery.

暂无摘要。

OBJECTIVE: Report the clinical findings, risk factors, treatment, and visual outcomes associated with Streptococcus endophthalmitis in comparison to culture-positive endophthalmitis associated with non-Streptococcus species.
METHODS: A retrospective chart review of adults between 18 and 89 years of age diagnosed with exogenous culture-positive endophthalmitis between January 1, 2009, and January 1, 2018, at the Duke Eye Center (Durham, North Carolina) with at least six months of follow-up from time of initial diagnosis was conducted. Clinical data including patient demographics, ocular history, baseline corrected visual acuity (VA) prior to presentation, time to presentation, presenting exam findings, VA at presentation, presumed etiology of endophthalmitis, medical and surgical management, and VA at the six-month follow-up was extracted and statistically analyzed.
RESULTS: Fifty-six eyes from 56 patients with culture-positive endophthalmitis were identified. Eyes with Streptococcus (n=18) had elevated intraocular pressure (IOP) at presentation (p=0.002), worse mean VA (Snellen) at presentation (20/14159 vs. 20/3098, p<0.001), and worse mean VA (Snellen) at six months (20/3475 vs. 20/235, p<0.001) compared to non-Streptococcus cases (n=38). Time to presentation (days) (median, IQR) was longer in eyes that underwent glaucoma surgery for both Streptococcus (2241 (836, 3709) vs. 3 (2, 31), p=0.003) and non-Streptococcus endophthalmitis (1236 (125, 3582) vs. 6 (4, 25), p<0.0001). There was no difference in VA at six months between Streptococcus and non-Streptococcus eyes based on treatment.  Conclusions: Streptococci are rare but important causes of exogenous endophthalmitis, and in our study, they were associated with worse visual outcomes than non-Streptococci. A history of any glaucoma surgery, even procedures performed years earlier, should be elicited when evaluating patients with ocular symptoms.

UNASSIGNED: Endophthalmitis is a severe infection accompanied by inflammation that affects the anterior and posterior parts of the eye. It is typically treated with a combination of antibiotics that cover various microorganisms. However, retinal pigment epithelium (RPE) cells are highly susceptible to damage from intravitreal injection therapy. This study aimed to investigate the impact of clinically relevant concentrations of meropenem (alone or in combination with vancomycin) on the viability and inflammation of RPE cells.
UNASSIGNED: In-vitro Study.
UNASSIGNED: RPE cells from passages 5-7 were treated with different concentrations of meropenem (1/4x, x, and 4x; [x = 16 mg/L]), vancomycin (30 mg/L), and meropenem (x) plus vancomycin for 24 h. The morphology assessment and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay were performed to evaluate cytotoxicity due to drug treatment. Real-time PCR was used to measure the relative expression of apoptotic genes (BCL-2 and BAX) and inflammation biomarkers (IL-1b and IL-6).
UNASSIGNED: Meropenem (alone or in combination with vancomycin) did not have any significant effect on RPE cell morphology, density, and viability. Gene expression analysis confirmed these results, showing no significant changes in the BCL-2/BAX ratio in drug-treated RPE cells compared to controls. Treatment with meropenem significantly induced the expression of IL-1b at all studied concentrations. Additionally, at concentrations of x and 4x, it also significantly increased the expression of IL-6, which was dose-dependent. However, this effect was not observed with vancomycin alone or in combination with meropenem.
UNASSIGNED: The results of this study suggest that meropenem, either alone or in combination with vancomycin, does not induce RPE cytotoxicity. There was an upregulation of IL-1b and IL-6 in meropenem monotherapy, the clinical implication of which should be elucidated in future in-vivo or clinical studies.

BACKGROUND: Endophthalmitis is a clinical diagnosis but identification of the disease-causing agent or agents allows for a more tailored treatment. This is routinely done through intraocular fluid cultures and staining. However, culture-negative endophthalmitis is a relatively common occurrence, and a causative organism cannot be identified. Thus, further diagnostic testing, such as pan-bacterial and pan-fungal polymerase chain reactions (PCRs), may be required. BODY: There are now newer, other testing modalities, specifically pan-bacterial and pan-fungal PCRs, that may allow ophthalmologists to isolate a causative agent when quantitative PCRs and cultures remain negative. We present a case report in which pan-fungal PCR was the only test, amongst quantitative PCRs, cultures, and biopsies, that was able to identify a pathogen in endophthalmitis. Pan-PCR has unique advantages over quantitative PCR in that it does not have a propensity for false-positive results due to contamination. Conversely, pan-PCR has drawbacks, including its inability to detect viruses and parasites and its increased turnaround time and cost. Based on two large retrospective studies, pan-PCR was determined not to be recommended in routine cases of systemic infection as it does not typically add value to the diagnostic workup and does not change the treatment course in most cases. However, in cases like the one presented, pan-bacterial and pan-fungal PCRs may be considered if empiric treatment fails or if the infective organism cannot be isolated. If pan-PCR remains negative or endophthalmitis continues to persist, an even newer form of testing, next-generation sequencing, may aid in the diagnostic workup of culture-negative endophthalmitis.
CONCLUSIONS: Pan-bacterial and pan-fungal PCR testing is a relatively new diagnostic tool with unique advantages and drawbacks compared to traditional culturing and PCR methods. Similar to the tests\' use in non-ophthalmic systemic infections, pan-bacterial and pan-fungal PCRs are unlikely to become the initial diagnosis test and completely replace culture methods. However, they can provide useful diagnostic information if an infectious agent is unable to be identified with traditional methods or if empiric treatment of endophthalmitis continues to fail.