Pathobiology of Fungal Endophthalmitis: A Major Review.

Fungal endophthalmitis is a chronic inflammatory condition of the eye's posterior segment that can lead to irreversible vision loss. While relatively rare in western countries, its incidence is notably higher in Asia, particularly India. The condition's prevalence is exacerbated by factors such as intravenous drug use, antibiotics, and ocular surgeries. Fungal endophthalmitis can be categorized as endogenous, arising from systemic infection, or exogenous, linked to external sources such as trauma or surgery. The fungal agents responsible vary by region, with Candida species common in the West and Aspergillus and Fusarium species more prevalent in India. Management typically involves vitrectomy and intravitreal antifungal drugs such as amphotericin B and voriconazole, though treatment is often complicated by multidrug resistance and culture-negative cases. Recent proteomic and transcriptomic analyses have highlighted the early and sustained activation of the host immune response during infection involving key inflammatory and oxidative stress-related proteins. Given the potential for excessive inflammation to cause retinal damage, targeted immunotherapies are crucial. Immunomodulation, which aims to balance the immune response, shows promise in preserving vision while effectively combating the infection. Key targets for immunomodulation include pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17), chemokines (CCL2, CXCL8), Toll-like receptors (TLR2, TLR4), and the complement system. Additionally, modulating the activity of macrophages, neutrophils, regulatory T cells, and Th17 cells, as well as targeting inflammasomes, can help control inflammation. Biologic agents and small molecule inhibitors offer further avenues for precise immune response modulation. This review underscores the importance of a comprehensive understanding of host-pathogen interactions in the development of effective therapies for fungal endophthalmitis.

HYPERACUTE CUTIBACTERIUM ACNES ENDOPHTHALMITIS AFTER CATARACT SURGERY.

PURPOSE: Postoperative endophthalmitis is a relatively uncommon, but potentially visually devastating, complication associated with cataract surgery. Specific microbial causes of endophthalmitis are characteristically associated with particular disease time courses. Although Cutibacterium acnes is typically associated with an indolent course of inflammation, we report a case of C. acnes endophthalmitis with onset on postoperative day (POD) 1 and a positive culture from POD 2. METHODS: This is a case report. RESULTS: A 56-year-old man underwent cataract extraction and posterior chamber intraocular lens placement in his left eye. On POD 1, he presented with severe discomfort, reduced visual acuity, and significant inflammation. On POD 2, his anterior chamber was tapped and injected with broad-spectrum antibiotics and steroids. The inflammation ultimately resolved, and his visual acuity improved to 20/20. CONCLUSION: C. acnes is a rare cause of hyperacute-onset postoperative endophthalmitis. Maintaining a high clinical suspicion and initiating prompt treatment can help to optimize long-term visual outcomes.

Endophthalmitis Rates and Types of Treatments After Intraocular Procedures.

Importance: Long-term trend analyses of overall endophthalmitis rates and treatment patterns are scarce. It is also unknown if the deviation from the recommendations of the Endophthalmitis Vitrectomy Study toward decreased utilization of vitrectomy is associated with different vision outcomes. Objective: To determine whether the rate of endophthalmitis after intraocular procedures or the primary treatment (prompt vitrectomy vs tap and inject) for endophthalmitis has changed over the past 20 years. Design, Setting, and Participants: This cohort study examined data for cohorts created by querying for different intraocular procedures, including intravitreal injections and surgeries for cataract removal, glaucoma, retinal conditions, and corneal transplants from 2000 to 2022. The data source was a US administrative medical claims database comprising commercial and Medicare Advantage insurance plans. Any intraocular procedure with at least 6 months of data available before and 6 weeks after the procedure was eligible. Exclusion criteria consisted of any previous diagnosis of endophthalmitis or another intraocular procedure during the follow-up period. Main Outcome Measure: The main outcomes were rate of postprocedure endophthalmitis and relative rate of prompt vitrectomy (vs tap and inject) as the primary method of treatment. Results: Among 2 124 964 patients, the mean (SD) age was 71.4 (10.2) years; 1 230 320 were female and 894 414 male. Over 22 years, 5 827 809 intraocular procedures were analyzed with 4305 cases of endophthalmitis found for an overall endophthalmitis rate of 0.07%. The yearly rate of endophthalmitis varied but generally declined from a high of 7 cases per 3502 procedures (0.20%) in 2000 to a low of 163 cases per 332 159 procedures (0.05%) in 2022. The percentage of cases treated with prompt vitrectomy also varied but generally declined over time with a high of 17 of 35 (48.6%) in 2003 and a low of 60 of 515 (11.6%) in 2021. Multivariable analysis of the endophthalmitis incidence rate ratio (IRR) showed a per-year decrease of 2.7% (IRR, 0.97; 95% CI, 0.97-0.98; P < .001) over the study period. A similar analysis also showed that the incidence rate of prompt surgical treatment decreased by 3.8% per year throughout the study period (IRR, 0.96; 95% CI, 0.95-0.97; P < .001). Conclusions and Relevance: This study found that the incidence of endophthalmitis following intraocular procedures appears to have decreased substantially over the past 20 years while prompt vitrectomy is being used less frequently as primary treatment than in the past.

miR-27a-3p promotes inflammatory response in infectious endophthalmitis via targeting TSC1.

Infectious endophthalmitis (IE) poses a significant threat to vision. This study aimed to explore the impact of microRNA (miR)-27a-3p on inflammation in IE. A rat model was developed through intravitreal injection of lipopolysaccharide. Clinical and demographic data were collected for 54 participants: 31 diagnosed with IE and 23 non-infectious patients with idiopathic macular holes. Expression levels of miR-27a-3p and inflammatory genes were quantified via reverse transcription quantitative polymerase chain reaction. Concentrations of inflammatory cytokines in human vitreous samples were measured using enzyme-linked immunosorbent assay. In vitro studies were conducted to explore the target gene of miR-27a-3p. The final animal experiments further verified the role of miR-27a-3p and tuberous sclerosis complex (TSC)1 in inflammatory responses. Results showed that miR-27a-3p was elevated in LPS-treated rats and IE patients. Thirty-one IE patients were divided into the High (n = 15) and Low (n = 16) groups according to the expression of miR-27a-3p. No significant differences were observed in baseline clinical and demographic characteristics between the control and IE patient groups. Pro-inflammatory cytokine mRNA levels and concentrations were notably increased in both LPS-treated rats and the High group of patients. Besides, results showed that TSC1 is a target gene of miR-27a-3p. Moreover, TSC1 inhibition promoted inflammation in rat vitreous samples. In summary, our findings suggested that miR-27a-3p exacerbated inflammatory responses in IE though targeting TSC1, offering novel insights for potential therapeutic strategies targeting miR-27a-3p in the clinical management of IE.

Design and Validation of Endophthalmitis Infectivity Measurement Algorithm in Post Cataract Acute Endophthalmitis: EMS Report No. 6.

Purpose: We constructed a clinical clue-based algorithm to identify the microbiology-positive post-cataract surgery endophthalmitis. Methods: 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. Results: 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). Conclusions: EIMA identified microbiology-positive endophthalmitis three-quarters of the time. Translational Relevance: EIMA suggested infectivity and the class of microbial infection could help targeted management of endophthalmitis after cataract surgery.

Anterior Segment Complications Following Intravitreal Injection.

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.

Electroretinographic Evaluations of Eyes With Endophthalmitis.

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. Translational Relevance: Simple and non-time-consuming ERG evaluations are helpful in evaluating the retinal function in eyes with endophthalmitis and predicting the visual prognosis.

POSTINTRAVITREAL INJECTION AND POSTCATARACT EXTRACTION ENDOPHTHALMITIS VISUAL OUTCOMES BY ORGANISM: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PURPOSE: To compare visual outcomes of endophthalmitis following intravitreal injections (IVIs) and cataract extraction by causative organism. METHODS: Searches in Cochrane Central Register of Controlled Trials, MEDLINE, and Embase identified articles reporting visual outcomes by causative organisms in post-IVI and cataract extraction endophthalmitis cases from January 2010 to February 2022. A random-effects meta-analysis compared visual improvement among endophthalmitis cases caused by causative organisms. RESULTS: Eighty-five out of 3,317 retrieved studies were included. The highest degree of visual acuity improvement in both post-IVI and postcataract extraction endophthalmitis was seen in cases caused by coagulase-negative staphylococci, followed by gram-negative organisms and other gram-positive organisms such as streptococci and enterococci. Culture-negative cases showed more visual acuity improvement than culture-positive cases in post-IVI endophthalmitis. These results remained consistent when accounting for endophthalmitis treatment, IVI type, condition requiring IVI treatment, follow-up period, and initial preprocedural visual acuity. CONCLUSION: Coagulase-negative staphylococci and gram-negative organisms show the most visual acuity improvement in both post-IVI and postcataract extraction endophthalmitis. Other gram-positive organisms such as streptococci and enterococci are associated with less visual improvement. This updated systematic review and meta-analysis revealed that the results of the Endophthalmitis Vitrectomy Study are consistent decades later despite advancements in surgical practices and the evolution of microorganisms over time.

Analysis of association of bandage contact lens with serious vision-threatening diseases and their management.

BACKGROUND: Bandage contact lenses are important aids for aftercare following ocular surgery and for a wide variety of ocular surface conditions. However, bandage contact lenses also bear the risk of fostering microbial infections of the cornea. We herein report the safety profile of bandage contact lenses from a comprehensive review of medical records in a tertiary care eye hospital in Germany. METHODS: We identified 638 consecutive patients who had been prescribed at least one bandage lens during the past 10 years. For these, we performed a computerized search for the following adverse events: (1) endophthalmitis, (2) emergency keratoplasty and (3) vision loss of at least 2 lines according to the Early Treatment Diabetic Retinopathy Study (ETDRS). We manually assessed the relatedness of each event to the bandage lens. Events later than 100 days following the bandage lens prescription were not considered to be related to bandage contact lenses. RESULTS: We observed 267 adverse events, with 120 occurring within 100 days after bandage lens prescription. This left a total of 18 endophthalmitis events, 21 penetrating keratoplasties and 81 eyes with vision loss of at least 2 ETDRS lines (for individual review of relatedness). Only two episodes of endophthalmitis could be linked to bandage lens wear. All other adverse events were due to causative conditions that had already been present prior to bandage contact lens insertion. CONCLUSIONS: Severe adverse events after bandage contact lens wear are not uncommon because lenses are used in patients suffering from preexisting ocular conditions. However, severe adverse events were almost never caused by the bandage contact lenses directly in our hands. We therefore conclude that bandage contact lenses are safe given proper ophthalmological supervision.

Brolucizumab-associated intraocular inflammation in Indian patients by VRSI study group.

CONTEXT: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. PURPOSE: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. SETTINGS AND DESIGN: Retrospective multicentric, survey-based study. METHODS: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. RESULTS: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. CONCLUSIONS: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.

Clinical characteristics and management outcome of acute infectious endophthalmitis.

PURPOSE: This study aimed to investigate the demographics, clinical characteristics, and management outcomes of patients with acute infectious endophthalmitis (AIE). METHODS: This retrospective chart review was conducted on all patients admitted with the clinical diagnosis of infectious endophthalmitis from 2017 to 2022. Demographic data, patients' clinical characteristics, the type of acute infectious endophthalmitis (post-operative, post-traumatic, bleb-associated, and endogenous endophthalmitis), the type of surgical procedure in the post-operative cases, the microbiologic analysis results of vitreous samples, therapeutic measures, and visual outcomes of patients were recorded. RESULTS: In this study, 182 participants, including 122 male (67%) and 60 (33%) female, were involved. The mean age of patients was 54.56 ± 21 years, with a range of 1-88 years old. The most prevalent type of AIE was post-operative (59.9%), followed by endogenous (19.2%), post-traumatic (17%), and bleb-associated (3.8%). The most common type of intraocular surgery in the post-operative subgroups of AIE patients was phacoemulsification (57.8%). The median (interquartile range) of the primary and final BCVA of patients was 1.5 (1.35, 1.85) and 0.65 (0.35, 1.35), respectively. Vitreous haziness grade (OR, 2.89; 95% CI, 1.11-5.74; p = 0.009) and the primary VA (OR, 60.34; 95% CI, 2.87-126.8; p = 0.008) revealed statistical significance for final vision loss. CONCLUSION: AIE is a devastating condition with poor visual outcomes, which presents with acute inflammatory signs and symptoms regardless of its type. However, prompt and appropriate treatment leads to visual recovery to a functional level in many patients.

Three-year epidemiological analysis of penetrating ocular traumatic endophthalmitis.

The characteristics of patients with endophthalmitis due to penetrating ocular trauma are still limited. The aim of the study was to fill these gaps among Chinese population. This retrospective study included patients diagnosed as penetrating ocular traumatic endophthalmitis between January 2016 to December 2018. During the past 3-year period, a total of 201 patients with antecedent penetrating eye injuries were evaluated. Of which, 42 (20.9%) patients presented a clinical course compatible with acute infectious endophthalmitis. 39 (92.86%) patients were males, and 15 (35.71%) patients had mechanical injuries from intraocular foreign body (IOFB), the rate of endophthalmitis due to IOFB was 13.43%, higher to the rate among patients without IOFB (7.46%). The duration between injury occurrence and endophthalmitis onset was 1 day in 10 (23,80%) patients; 2 to 7 days in 31 (73.80%) patients, and 7 to 14 days in 1 (2.38%) patient. After 1 year follow-up, best corrected visual acuity (BCVA) better than 20/400 was observed in 15 (35.71%) patients, counting fingers and hand move in 17 (40.48%) patients, light perception in 5 (11.9%) patients and no light perception in 5 (11.9%) patients, respectively. Patients with promising outcomes had better initial BCVA at baseline (P < .001). Endophthalmitis is a severe ocular infectious condition that may lead to irreversible vision loss. A greater attention must be paid to penetrating eye injuries within males, who had poor BCVA at baseline, particularly with obvious IOFB.

Clinical features, treatment and prognosis of patients with endogenous infectious endophthalmitis.

PURPOSE: To investigate whether the clinical characteristics, treatment and prognosis of endogenous infectious endophthalmitis (EIE) have changed over the past 5 years. METHODS: Retrospectively analyze all articles about EIE published in the PubMed, Web of Science, and Embase databases from 2017 to 2021. RESULTS: A total of 128 patients and 147 eyes (46 left and 60 right) were included in the study. The mean age at diagnosis was 51 ± 19 years. The most common risk factors were diabetes and intravenous drug use. From 2017 to 2021, Klebsiella was the most common pathogenic microorganism (22%), and vitreous culture had the highest positivity rate. The most common complaint was blurred vision. The mean visual acuity (logMAR) at onset was 2.84, and the clinical symptoms were vitreal inflammation and opacity (63%), ocular pain (37%), and conjunctival congestion (36%). The ocular inflammation could be reduced by intraocular antibiotics or vitrectomy. However, the visual prognosis, with a mean logMAR of 2.73; only 50% of the eyes reached a visual acuity level of finger count and above. Changes in diagnostics over the past 5 years have mainly manifested as more diverse microorganism culture methods. In addition to conventional culture methods, PCR, sputum culture and aqueous humour culture are also commonly used for the diagnosis of pathogenic bacteria, improving the positive culture rate and visual prognosis. CONCLUSION: The prognosis of EIE is poor. It is recommended to pay attention to the pathogenic bacteria culture results and accompanying systemic diseases and to diagnose and treat patients as soon as possible.

Endogenous endophthalmitis caused by Streptococcus mitis: A case report.

RATIONALE: Endogenous endophthalmitis is a rare disease caused by hematogenous intraocular metastasis of bacteria from an infectious source. Diagnosing endogenous endophthalmitis is challenging for non-ophthalmologists. However, ophthalmic diseases can cause irreversible vision loss, making prompt diagnosis and treatment critical. Here we present a rare case of endogenous endophthalmitis initially misdiagnosed as a cataract. PATIENT CONCERNS: An 84-year-old Japanese man presented to the emergency department with fever and dysmotility. The patient was aware of a left subconjunctival hemorrhage and cloudy cornea upon arrival at the hospital, but he misunderstood it as a fall-induced subconjunctival hemorrhage and age-related cataracts. DIAGNOSES: On the day following admission, petechial hemorrhage on the eyelid conjunctiva and the detection of Streptococcus mitis in the blood culture results led us to suspect endophthalmitis rather than cataracts. A definitive diagnosis of endophthalmitis was made through ophthalmologic examinations, and endophthalmitis was considered secondary to endocarditis. INTERVENTIONS: Subsequently, antimicrobial treatment was continued. OUTCOMES: However, the patient developed myocardial infarction and died on the ninth day of hospitalization. LESSONS: Two important lessons were learned from the examination of this case of endogenous endophthalmitis caused by S mitis. First, endophthalmitis and cataracts can be misdiagnosed. Because the symptoms of endophthalmitis and cataracts, such as decreased vision, photophobia, and blurred vision, are similar, the eye must be cautiously examined. Second, endocarditis caused by S mitis may lead to endogenous endophthalmitis. Although S mitis is not pathogenic, endogenous endophthalmitis may occur in patients with certain risk factors, such as older age, cancer, and immunosuppression.

In vivo and in vitro efficacy of the ithmid kohl/zinc-oxide nanoparticles, ithmid kohl/Aloe vera, and zinc-oxide nanoparticles/Aloe vera for the treatment of bacterial endophthalmitis.

The aim of this study was to investigate the efficacy of the ithmid kohl/zinc-oxide nanoparticles (ZnONPs), ithmid kohl/Aloe vera, and ZnONPs/Aloe vera in the treatment of bacterial endophthalmitis. The endophthalmitis model was prepared by contaminating both eyes of 24 healthy adult male albino rabbits with a clinical isolate of Klebsiella pneumoniae. The animals were randomly divided into eight groups (A-H) according to the treatment. Group A received 1 ml of ithmid kohl/ZnONPs ointment, group B received 1 ml of ithmid kohl/Aloe vera gel ointment, group C received 1 ml of ZnONPs/Aloe vera gel ointment, and groups D, E, and F were treated with 1 ml of ithmid kohl solution (0.5 g/ml in distilled water), 1 ml of ZnONPs (0.5 g/ml) colloidal dispersion, and 1 ml of Aloe vera gel, respectively. Group G received 100 µl of a tetracycline antibiotic solution (final concentration: 16 µg/ml), and group H received sterile distilled water (no treatment). In vitro antibacterial activity was evaluated against K. pneumoniae using the agar well diffusion. The combination of ithmid kohl/ZnONPs was the most effective formulation for treating endophthalmitis model in infected rabbits within 2 days. In vitro antibacterial assay confirmed the potential of the ithmid kohl/ZnONPs formulation, which had the largest zone of inhibition (31 mm) among the compounds tested. The preparation of the ithmid kohl/ZnONPs formulation and its in vivo experiment in albino rabbits for the treatment of bacterial endophthalmitis was an innovative approach that has shown promise and may potentially serve as a viable alternative in clinical practice.