Microbial keratitis in Southern Malawi: a microbiological pilot study.

OBJECTIVE: Microbial keratitis (MK) is a significant cause of blindness in sub-Saharan Africa. We investigated the feasibility of using a novel corneal impression membrane (CIM) for obtaining and processing samples by culture, PCR and whole-genome sequencing (WGS) in patients presenting with suspected MK in Malawi. METHODS AND ANALYSIS: Samples were collected from patients presenting with suspected MK using a 12 mm diameter polytetrafluoroethylene CIM disc. Samples were processed using culture and PCR for Acanthamoeba, herpes simplex virus type 1 (HSV-1) and the bacterial 16S rRNA gene. Minimum inhibitory concentrations of isolates to eight antimicrobials were measured using susceptibility strips. WGS was used to characterise Staphylococcus aureus isolates. RESULTS: 71 eyes of 71 patients were included. The overall CIM isolation rate was 81.7% (58 positive samples from 71 participants). 69 (81.2%) of isolates were Gram-positive cocci. Coagulase-negative Staphylococcus 31.8% and Streptococcus species 14.1% were the most isolated bacteria. Seven (9.9%) participants were positive for HSV-1. Fungi and Acanthamoeba were not detected. Moxifloxacin and chloramphenicol offered the best coverage for both Gram-positive and Gram-negative isolates when susceptibility was determined using known antimicrobial first quartile concentrations and European Committee on Antimicrobial Susceptibility Testing breakpoints, respectively. WGS identified known virulence genes associated with S. aureus keratitis. CONCLUSIONS: In a resource-poor setting, a CIM can be used to safely sample the cornea in patients presenting with suspected MK, enabling identification of causative microorganisms by culture and PCR. Although the microbiological spectrum found was limited to the dry season, these preliminary results could be used to guide empirical treatment.

Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

Purpose: The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. Methods: A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Results: Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. Conclusion: The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Ferroptosis as a Potential Therapeutic Target for Reducing Inflammation and Corneal Scarring in Bacterial Keratitis.

Purpose: Bacterial keratitis (BK) is a serious ocular infection that can cause severe inflammation and corneal scarring, leading to vision loss. In this study, we aimed to investigate the involvement of ferroptosis in the pathogenesis of BK. Methods: Transcriptome analysis was performed to evaluate ferroptosis-related gene expression in human BK corneas. Subsequently, the ferroptosis in mouse models of Pseudomonas aeruginosa keratitis and corneal stromal stem cells (CSSCs) were validated. The mice were treated with levofloxacin (LEV) or levofloxacin combined with ferrostatin-1 (LEV+Fer-1). CSSCs were treated with lipopolysaccharide (LPS) or LPS combined Fer-1. Inflammatory cytokines, α-SMA, and ferroptosis-related regulators were evaluated by RT-qPCR, immunostaining, and Western blot. Iron and reactive oxygen species (ROS) were measured. Results: Transcriptome analysis revealed significant alterations in ferroptosis-related genes in human BK corneas. In the BK mouse models, the group treated with LEV+Fer-1 exhibited reduced inflammatory cytokines (MPO, TNF-α, and IFN-γ), decreased corneal scarring and α-SMA expression, and lower Fe3+ compared to the BK and LEV groups. Notably, the LEV+Fer-1 group showed elevated GPX4 and SLC7A11 in contrast to the BK and LEV group. In vitro, Fer-1 treatment effectively restored the alterations of ROS, Fe2+, GPX4, and SLC7A11 induced by LPS in CSSCs. Conclusions: Ferroptosis plays a crucial role in the pathogenesis of BK. The inhibition of ferroptosis holds promise for mitigating inflammation, reducing corneal scarring, and ultimately enhancing the prognosis of BK. Consequently, this study provides a potential target for innovative therapeutic strategies for BK, which holds immense potential to transform the treatment of BK.

Factors Associated With Laboratory Test Negativity Following a Transition in Specimen Collection in Microbial Keratitis Cases.

PURPOSE: Negative laboratory results make targeting microbial keratitis treatment difficult. We investigated factors associated with laboratory negativity in patients with microbial keratitis in the context of a transition to a new specimen collection method. METHODS: Microbial keratitis patients with associated laboratory tests were identified in the electronic health record of a tertiary care facility from August 2012 to April 2022. Patient demographics and laboratory results were obtained. Random sampling of 50% of charts was performed to assess the impact of the ocular history and pretreatment measures. The relationship between probability of negative laboratory results with demographics, ocular history, pretreatment measures, and utilization of a new specimen collection method (i.e. ESwab) was evaluated by multivariable logistic regression. RESULTS: Of 3395 microbial keratitis patients identified, 31% (n = 1051) had laboratory tests. Laboratory testing increased over time (slope = 2.5% per year, p < 0.001; 19.6% in 2013 to 42.2% in 2021). Laboratory negative rate increased over time (slope = 2.2% per year, p = 0.022; 48.5% in 2013 to 62.3% in 2021). Almost one-third of patients (31.2%, n = 164) were pretreated with steroids. Over two-thirds of patients were pretreated with antibiotics (69.5%, n = 367). 56.5% (n = 297) of patients were outside referrals. In multivariable regression, patients with corticosteroid pretreatment had lower odds of negative laboratory results (odds ratio [OR] = 0.49, p = 0.001). There were higher odds of negative laboratory results for every additional antibiotic prescribed to a patient prior to presentation (OR = 1.30, p = 0.006) and for specimens collected using ESwabs (OR = 1.69, p = 0.005). Age, prior eye trauma, outside referrals, and contact lens wear were not significantly associated with negative laboratory results. CONCLUSION: More microbial keratitis associated laboratory tests are being taken over time. Over 60% of tests were negative by 2022. Factors associated with negative laboratory test results included pretreatment with antibiotics and specimens collected with the new collection method.

NO EFFECT OF REAL-WORLD UNIVERSAL FACE MASKING ON POST-INTRAVITREAL INJECTION ENDOPHTHALMITIS RATE AT A SINGLE TERTIARY ACADEMIC CENTER.

PURPOSE: To determine whether universal masking during COVID-19 altered rate and outcomes of postinjection endophthalmitis. METHODS: Retrospective, single-site, comparative, cohort study. Eyes diagnosed with endophthalmitis within 4 weeks of intravitreal injection at the University of Michigan from August 1, 2012, to November 15, 2022, were identified. Cases were considered "masking" between March 15, 2020, and November 15, 2022. Endophthalmitis rate, visual acuity, and microbial spectrum were investigated. RESULTS: There were 20 postinjection endophthalmitis cases out of 72,194 injections (0.028%; one in 3,571 injections) premasking and 10 of 38,962 with universal masking (0.026%; one in 3,846 injections; odds ratio 0.9; 95% [confidence interval]: 0.4-2.0). Referral from the community was unchanged with 32 cases referred premasking (0.35 cases/month) and 10 cases with masking (0.31 cases/month). Presenting mean the logarithm of the minimum angle of resolution visual acuity with masking of all postinjection endophthalmitis cases trended worse (2.35 ± 0.40) compared with premasking (2.09 ± 0.48; P = 0.05) with light perception visual acuity more common with masking (31.6% vs. 10.9%, P = 0.06). There was no delay in time from procedure to initial treatment ( P = 0.36), no difference in the rate of initial treatment with tap and inject (T/I), and similar positive-culture rates ( P = 0.77) between the cohorts. Visual acuity after 30 days of follow-up was clinically unchanged (∼20/500 vs. 20/400; P = 0.59). CONCLUSION: Universal masking had no effect on postinjection endophthalmitis rate or on the rate of culture-positive cases. Although presenting visual acuity appeared worse with masking, this was not statistically significant, and current treatment paradigms resulted in similar visual outcomes.

3D-Printed Inherently Antibacterial Contact Lens-Like Patches Carrying Antimicrobial Peptide Payload for Treating Bacterial Keratitis.

Delivery of therapeutic agents through contact lenses-like patches is a promising strategy to achieve significant bioavailability with negligible eye drainage. The present study investigates the preparation and 3D printing of mucoadhesive gelatin methacryloyl (GelMA)/chitosan methacryloyl (ChiMA) hydrogels to fabricate them as contact lens-like patches (CLP) loaded with antimicrobial peptide, S100A12 (AMP) for treating bacterial keratitis (BK). Extrusion technology is used to print the patches layer by layer to form a hemispherical scaffold suitable for eyewear, and 3D-printed CLP is crosslinked using Irgacure 2959 under UV light. The results from the in vivo experiment conducted on Pseudomonas aeruginosa-infected BK rabbit model after the treatment with AMP-loaded CLP have shown a significant decrease in bacterial load when plated for CFU. The newly developed delivery system containing AMP has great potential to overcome the treatment challenges of multidrug resistance (MDR) in bacteria and eliminate the frequent dosing associated with eye drops. The presence of chitosan in the formulation provides a synergetic effect on the AMP in disrupting bacterial biofilms. The ease of using 3D printing will open new avenues for optimizing the dosage depending on the severity of the BK in the patients, which can be used as personalized medicine.

A Comparison of Culture Results and Visual Acuity in Contact Lens Related Microbial Keratitis.

PURPOSE: Evaluate the effect of corneal and contact lens-related (CLR) culture results on visual acuity (VA) in patients with microbial keratitis (MK). METHODS: MK patients with corneal and CLR cultures were identified in the University of Michigan electronic health record from August 2012 to April 2022. Test results were classified as laboratory-positive or laboratory-negative. Linear regression was used to examine trends of VA and associations between changes in VA (differences of VA at 90-day and baseline VA) and corneal and CLR culture results, after adjustment for baseline VA. One-sample t-tests were used to test if the slope estimates were different from zero. RESULTS: MK patients (n = 50) were on average 49 years old (standard deviation = 20.9), 56% female, and 90% White. Positive corneal and CLR cultures were reported in 60% and 64% of patients, respectively, and 38% reported both. The agreement rate between corneal and CLR culture results was 30% (n = 15/50). LogMAR VA improved over time in patients with positive corneal and CLR cultures (Estimate=-0.19 per 10-day increase, p = 0.002), and in those with negative corneal and positive CLR cultures (Estimate= -0.17 per 10-day increase, p = 0.004). Compared to patients with negative corneal and CLR cultures, there was a trend toward improvement in VA for patients with positive corneal and CLR cultures (Estimate=-0.68, p = 0.068), and those with negative corneal and positive CLR cultures (Estimate= -0.74, p = 0.059), after adjusting for baseline VA. CONCLUSIONS: Positive CLR cultures are associated with significant improvement in VA over time. These additional cultures can provide guidance on appropriate antimicrobial selection, especially when corneal cultures are negative.

Intracameral antibiotics during cataract surgery: efficacy, safety, and cost-benefit considerations.

PURPOSE OF REVIEW: We summarize evidence-based considerations regarding the use of intracameral antibiotics during cataract surgery. RECENT FINDINGS: The use of intraoperative intracameral antibiotics reduced the incidence of postcataract surgery endophthalmitis 3.5-fold, with an odds ratio ranging from 0.14 to 0.19. A survey of the American Society of Cataract and Refractive Surgery showed usage of intracameral injections of antibiotics increased by 16% in the United States between 2014 and 2021. The frequency of vancomycin usage has sharply dropped to 6%, while moxifloxacin is now the dominant choice at 83% among respondents. One analysis showed that 2500 patients need to be treated with intracameral antibiotics to prevent one case of endophthalmitis. A 500 µg intracameral moxifloxacin at $22 dollars per dose is cost-effective, including for patients with posterior capsular rupture (PCR). SUMMARY: Studies substantiate the safety and efficacy of intracameral antibiotics for endophthalmitis prophylaxis. Intracameral moxifloxacin and cefuroxime are the most common choices. While vancomycin shows potential for efficacy, further studies evaluating clinical outcomes are needed. Adverse events are rare and commonly due to errors in preparation. Topical antibiotics do not provide additional prophylactic benefits to intracameral regimens. Intracameral antibiotics given alone are cost-effective.

A Case Series of Ocular Syphilis Cases at Military Treatment Facility From 2020 to 2021.

Syphilis is a sexually transmitted infection, caused by the spirochete Treponema pallidum, that can lead to multi-organ involvement. In 2020, over 138,000 cases were reported in the United States equating to a case report of 40.8 per 100,000 people. Ocular syphilis is a rare manifestation and is defined as the clinical presentation of ocular disease in a person with laboratory-confirmed syphilis infection of any stage, with estimated incidence of 0.6-2% of all cases. Syphilis is known as "The Great Imitator," and can present as nearly any form of ocular disease, though the most common manifestations are posterior uveitis and panuveitis. The highly variable clinical presentation of ocular syphilis often leads to delayed diagnosis allowing the potential for poor, often preventable outcomes. This highlights the need for providers to have a high level of clinical suspicion and awareness of ocular manifestations of syphilis, especially in high risk populations. We present a case series of five patients diagnosed with ocular syphilis at a military treatment facility. Each patient had different presenting symptoms as well as different ocular manifestations.

AGGREGATIBACTER ENDOPHTHALMITIS IN A PATIENT WITH DENTOPHOBIA.

PURPOSE: To describe a rare case of unilateral, endogenous endophthalmitis caused by Aggregatibacter aphrophilus (HACEK group) confirmed in vitreous and blood cultures, in a patient with dentophobia. METHODS: Case report. PATIENTS: A seventy-five-year-old male patient with Type 2 diabetes, previous myocardial infarction, and pacemaker implantation. RESULTS: Patient was observed with sudden loss of vision at the Department of Ophthalmology, Uppsala University. Initial diagnosis was posterior vitreous detachment and anterior uveitis, but progression of disease led to vitrectomy, which actually demonstrated endophthalmitis and growth of A. aphrophilus of the HACEK group. Aggregatibacter bacteremia and pacemaker endocarditis were also identified and dental examination confirmed growth of Aggregatibacter in the oral cavity. Intravitreal treatment with ceftazidime and vancomycin according to Endophthalmitis Vitrectomy Study protocol was administered with quick resolution of endophthalmitis. CONCLUSION: Aggregatibacter endophthalmitis is a rare, but devastating cause of vision loss where immediate diagnosis may be delayed. Prompt diagnosis may be facilitated by a thorough medical history and early vitreous biopsy. Systemic investigation by an infectious disease specialist and multidisciplinary assessment are mandatory. Ophthalmologic treatment is effective with intravitreal injections of ceftazidime and vancomycin.

Ocular infections associated with atypical mycobacteria: A review.

Atypical mycobacteria or non-tuberculous mycobacteria (NTM) are a group of acid-fast bacteria that are pathogenic to different parts of the eye. The organisms can cause a spectrum of ocular infections including keratitis, scleritis, uveitis, endophthalmitis and orbital cellulitis. Trauma, whether surgical or nonsurgical, has the highest correlation with development of this infection. Common surgeries after which these infections have been reported include laser in situ keratomileusis (LASIK) and scleral buckle surgery. The organism is noted to form biofilms with sequestration of the microbe at different inaccessible locations leading to high virulence. Collection of infective ocular material (corneal scraping/necrotic scleral tissue/abscess material/vitreous aspirate, etc.) and laboratory identification of the organism through microbiologic testing are vital for confirming presence of the infection and initiating treatment. In cluster infections, tracing the source of infection in the hospital setting via testing of different in-house samples is equally important to prevent further occurrences. Although the incidence of these infections is low, their presence can cause prolonged disease that may often be resistant to medical therapy alone. In this review, we describe the various types of NTM-ocular infections, their clinical presentation, laboratory diagnosis, management, and outcomes.

Evaluating the utility of inflammation score in post-cataract surgery endophthalmitis. Results from a prospective study in India. EMS Report #4.

PURPOSE: To investigate if inflammation score (IS), calculated from the cornea, anterior chamber, iris, and vitreous, indicates endophthalmitis severity. METHODS: In a prospective study, consecutive adults with a clinical diagnosis of post-cataract endophthalmitis within 6 weeks of surgery were recruited. Patients were allocated to IS-based primary treatment (IS < 10: intravitreal injection and IS ≥ 10: vitrectomy) and randomized to two intravitreal antibiotics combinations (vancomycin + ceftazidime and vancomycin + imipenem). Undiluted vitreous microbiology work-up included culture susceptibility, polymerase chain reaction, Sanger sequencing, and targeted next-generation sequencing. RESULTS: The average age of 175 people was 63.4 ± 10.7 years and included 52.6% small incision cataract surgery and 47.4% phacoemulsification surgery. Severe endophthalmitis (IS ≥ 20), diagnosed in 27.4% of people, had a shorter time to symptoms (average 5.4 vs 8.7 days; P = 0.018), poorer presenting vision (all ≤ hand motion), higher culture positivity (50% vs 30.7%; P = 0.032), and higher Gram-negative bacterial infection (70.8% vs 46.2%; P = 0.042). For IS ≥ 20 discriminant and Gram-negative infection, Spearman's coefficient was 0.7 [P < 0.0001, 95% confidence interval (CI) 0.59-0.82], with an area under the receiver operating characteristic curve of 0.9 (95% CI 0.85-0.94, P < 0.0001), a Youden index J of 0.74, a sensitivity of 87.2%, and a specificity of 87.5%. The final vision of >20/400 and >20/100 was regained in 50.2% and 29.1% of people, respectively. The susceptibility of common Gram-positive cocci and Gram-negative bacilli was the highest for vancomycin (95.0%) and colistin (88.6%), respectively. NGS detected polymicrobial infection in 88.5% of culture-negative endophthalmitis. CONCLUSIONS: Higher inflammation scores indicated severe disease and Gram-negative infection in post-cataract endophthalmitis.

[Ocular syphilis: alert for clinicians and ophthalmologists]. / Sífilis ocular: alerta para clínicos y oftalmólogos.

Syphilis is an infectious disease caused by the spirochete Treponema pallidum. It can cause ocular compromise at any stage, in immunocompetent or immunocompromised patients. Even though the ocular form is not frequent, due to the increase in the incidence of syphilis in recent years, it is mandatory to take it into consideration as a differential diagnosis in visual disorders. The most common clinical presentation is uveitis. Diagnosis is based on the presence of clinical signs and symptoms consistent with ophthalmologic involvement in a patient with syphilis. The CSF study should be performed on a clinical basis, to rule out concomitant neurological involvement. We present 5 cases of ocular syphilis, its clinical manifestations, treatment and evolution.

La sífilis es una enfermedad infecciosa causada por la espiroqueta Treponema pallidum. Puede producir compromiso ocular en cualquier estadio, en pacientes inmunocompetentes o inmunocomprometidos. Si bien la frecuencia de presentación de la forma ocular no es alta, debido al aumento de la incidencia de sífilis en los últimos años, es necesario tenerla en cuenta como diagnóstico diferencial en los trastornos visuales. La presentación clínica más frecuente es la uveítis. Se objetiva ante la presencia de signos y síntomas clínicos consistentes con afectación oftalmológica en un paciente con sífilis. El estudio del LCR debe realizarse ante la sospecha clínica, para descartar compromiso neurológico concomitante. Comunicamos 5 casos de sífilis ocular, sus manifestaciones clínicas, tratamiento y evolución.

Steroids in the Management of Infectious Keratitis.

PURPOSE: To summarize the evidence base on the use of topical corticosteroids for infectious keratitis. METHODS: Narrative review. RESULTS: Infectious keratitis is a painful condition that often results in visually significant corneal stromal scarring, even when antimicrobial therapy is successful. Corticosteroids may reduce inflammation and subsequent scar formation and while relieving the acute ocular pain associated with a corneal ulcer. However, corticosteroids also reduce the host immune response, which could hinder the ability to clear infection. The safety and effectiveness of corticosteroids depends to a large part on the efficacy of the antimicrobials being used to treat the underlying infection. Randomized trials have found that corticosteroids are safe and effective for herpetic keratitis when used with appropriate antiviral therapy, and are safe for bacterial keratitis when used with broad spectrum topical antibiotics. The effectiveness of corticosteroids for bacterial keratitis has not been shown conclusively, although more advanced bacterial corneal ulcers may do better with corticosteroids. No randomized trials have assessed the safety and effectiveness of steroids for fungal or acanthamoeba keratitis. Animal studies suggest corticosteroids may be harmful in fungal keratitis, and observational human studies have found that steroids are harmful for fungal and acanthamoeba keratitis when started prior to anti-amoebics. CONCLUSIONS: Topical corticosteroids, when used as an adjunct to antimicrobial therapy, may be beneficial if the antimicrobial being used can effectively clear or suppress the infection, such as in bacterial and herpetic keratitis. Randomized trials would be helpful to further delineate the role of corticosteroids for infectious keratitis.

Endophthalmitis associated with Staphylococcus cohnii after vitrectomy and silicone oil insertion: A case report.

BACKGROUND: To report a case of endophthalmitis in a silicone oil (SO)-filled eye associated with Staphylococcus cohnii. After vitrectomy, the environment for bacterial growth in the eye is removed, and SO has antibacterial effect on a variety of microorganisms. Endophthalmitis is seen in about 0.040% cases after pars plana vitrectomy and is even more uncommon in cases where SO is used. METHODS: The patient was diagnosed as endophthalmitis and admitted to our hospital for emergency. The main concern is if intraocular infection can be controlled and the visual prognosis. In this case, multiple intravitreal antibiotics injection and anterior chamber washout were performed. Not only that, phacoemulsification was performed. RESULTS: Hypopyon became less after 3 operations were performed. The infection was under control finally. CONCLUSION: To the best of our knowledge, it is the first report of S. cohnii endophthalmitis in an SO-filled globe of an middle-aged patient. It is important to treat infective endophthalmitis with antibiotics promptly. Delayed therapy may affect the visual prognosis.