Antimicrobial resistance in ocular infection: A review.

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.

Updates in Diagnostic Imaging for Infectious Keratitis: A Review.

Infectious keratitis (IK) is among the top five leading causes of blindness globally. Early diagnosis is needed to guide appropriate therapy to avoid complications such as vision impairment and blindness. Slit lamp microscopy and culture of corneal scrapes are key to diagnosing IK. Slit lamp photography was transformed when digital cameras and smartphones were invented. The digital camera or smartphone camera sensor's resolution, the resolution of the slit lamp and the focal length of the smartphone camera system are key to a high-quality slit lamp image. Alternative diagnostic tools include imaging, such as optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). OCT's advantage is its ability to accurately determine the depth and extent of the corneal ulceration, infiltrates and haze, therefore characterizing the severity and progression of the infection. However, OCT is not a preferred choice in the diagnostic tool package for infectious keratitis. Rather, IVCM is a great aid in the diagnosis of fungal and Acanthamoeba keratitis with overall sensitivities of 66-74% and 80-100% and specificity of 78-100% and 84-100%, respectively. Recently, deep learning (DL) models have been shown to be promising aids for the diagnosis of IK via image recognition. Most of the studies that have developed DL models to diagnose the different types of IK have utilised slit lamp photographs. Some studies have used extremely efficient single convolutional neural network algorithms to train their models, and others used ensemble approaches with variable results. Limitations of DL models include the need for large image datasets to train the models, the difficulty in finding special features of the different types of IK, the imbalance of training models, the lack of image protocols and misclassification bias, which need to be overcome to apply these models into real-world settings. Newer artificial intelligence technology that generates synthetic data, such as generative adversarial networks, may assist in overcoming some of these limitations of CNN models.

Presumed Microbial Keratitis Cases Resulting in Evisceration and Enucleation in Sydney, Australia.

PURPOSE: Describe presumed microbial keratitis cases resulting in evisceration/enucleation from 2012 to 2016 in Sydney, Australia. METHODS: A retrospective case review included 33 patients. Cases were identified from pathology and hospital coding data. Sociodemographic and clinical details were collated. RESULTS: Mean age was 79 years (range: 38-100 years), and 64% female. There were 30 eviscerations and 3 enucleations, at a median time of 8 days (range: 1-270 days) due to endophthalmitis (n = 15, 45%). Major ocular associated factors included topical corticosteroid use in 12 patients (36%), exposure keratopathy in 4 (12%), ectropion in 3 (9%), degenerative corneal disease in 3 (9%), and corneal graft in 2 (6%). Pseudomonas aeruginosa was the most common isolate with no reports of antimicrobial resistance. CONCLUSIONS: Educating elderly patients with a history of topical corticosteroid use, corneal or ocular surface disease about prompt hospital presentation and treatment of microbial keratitis may decrease the probability of losing the eye.

Knowledge, views and experiences of Australian optometrists in relation to ocular stem cell therapies.

CLINICAL RELEVANCE: Findings from this study examining Australian optometrists' insights into ocular stem cell (SC) therapies have capacity to inform continuing professional development (CPD) about these interventions. BACKGROUND: This study investigated Australian optometrists' knowledge, views, experiences, and preferred education sources regarding ocular SC therapies. METHODS: An online survey was distributed to optometrists via Optometry Australia, Mivision magazine, professional groups, and social media from August 2020 to March 2021. Data were collected on demographics, and SC knowledge, awareness and experience. RESULTS: Of 81 optometrists who completed the survey, many were metropolitan-based (85%), worked in independent practice (47%), female (56%) and >46 years of age (45%). Approximately one-fifth indicated awareness of ocular SC therapies used in standard practice; one-third had knowledge of SC clinical trials. The most noted SC therapies were for corneal disease in the United States [US] (72%) and Australia (44%). Respondents identified the availability of SC therapies for dry eye disease in Australia and the US (39% and 44% respectively), despite no regulatory-approved treatments for this indication. Clinical trials investigating inherited retinal and corneal diseases in Australia were the most commonly identified (44% and 36%, respectively). Half the respondents felt 'unsure' about the quality of evidence for treating eye conditions using SCs. One-fifth indicated concerns with these therapies; of these, most mentioned efficacy (82%), safety (76%) and/or cost (71%). About one-fifth reported being asked for advice about SCs by patients. Two-thirds felt neutral, uncomfortable, or very uncomfortable providing this advice, due to lack of knowledge or the topic being beyond their expertise. Over half (57%) were unsure if clinical management should change if patients received SC therapies. Respondents were receptive to face-to-face education. CONCLUSION: Some optometrists responding to this survey were aware of ocular SC therapies and/or clinical trials. CPD programs may assist with maintaining currency in this evolving field.

What is the effect of a low literacy talking book on patient knowledge, anxiety and communication before radiation therapy starts? A pilot study.

INTRODUCTION: Radiation therapy is a common cancer treatment, requiring timely information to help patients prepare for treatment. We pilot tested a low literacy, psycho-educational talking book (written booklet, with accompanying audio recording) to examine (i) the effect of the tool on knowledge, anxiety and communication; (ii) acceptability, and (iii) how it was used in appointments. METHODS: A pre-post design was employed. Patients scheduled to receive radiation therapy for any cancer were recruited from two hospitals in Sydney, Australia. Participants were sent the talking book before treatment planning and completed baseline and follow-up surveys, before and after the intervention. RESULTS: Forty participants were recruited, and 39 completed all study assessments. Overall, knowledge increased after receiving the talking book by 3.8 points from 13.9 to 17.7/20 (95% confidence interval (CI) 2.7, 4.8, P < 0.001). Anxiety and concerns were significantly lower after receiving the talking book (P = 0.015 and P = 0.004, respectively). Nearly half of participants (s = 17, 48%) reported using the book during appointments. Most reported finding it easier to communicate (n = 31, 89%) and to ask more questions (n = 21, 62%). CONCLUSION: The talking book shows promise in improving knowledge, reducing anxiety and enhancing communication. Strategies to support the implementation of the talking book are required. Further studies to translate the book into different languages are also planned.

Infectious keratitis: A review.

Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy.

Outcomes of Microbial Keratitis Cases Resistant to Antimicrobials in Sydney, Australia.

PURPOSE: The purpose of this study was to describe demographics, predisposing factors, clinical features, treatment, and outcomes of microbial keratitis cases resistant to antimicrobials. METHODS: A retrospective case series was conducted. All patients with microbial keratitis resistant to antimicrobials who underwent a corneal scrape and culture from 2012 to December 2016 at the Sydney Eye Hospital were included. Cases were identified from pathology and hospital coding data. Coagulase-negative staphylococci (CoNS), Staphylococcus aureus (S. aureus), and Corynebacterium spp. resistant to cefalotin, chloramphenicol, ciprofloxacin, or gentamicin were analyzed. RESULTS: One hundred fifteen episodes had a resistant CoNS, 24 S. aureus, and 12 Corynebacterium spp. Antimicrobial resistance was associated with older women (67%, median age 83 years) with Corynebacterium spp. (P < 0.001), corneal graft, and previous topical steroid use. Larger epithelial defects (P = 0.203) and infiltrates (P = 0.180) were more likely to be associated with Corynebacterium spp., but not statistically significant. At the initial and final visits, resistant S. aureus (75% vs. 67%) and Corynebacterium spp. (78% vs. 80%) cases were more likely to be classified as blind (>3/60) compared with CoNS (45% vs. 28%) (P = 0.011 vs. P = 0.004). Corneal perforation occurred more often in resistant S. aureus cases (P < 0.001), whereas slow and nonhealing epithelial defects needing other procedures were more likely to occur with resistant Corynebacterium spp. (P < 0.001). CONCLUSIONS: Patients with resistant CoNS were younger and presented with smaller ulcers and moderate vision loss. Visual and clinical outcomes were significantly better for resistant CoNS than for those with resistant S. aureus or Corynebacterium spp.

Predisposing factors, microbiological features and outcomes of patients with clinical presumed concomitant microbial and herpes simplex keratitis.

BACKGROUND/OBJECTIVES: To describe the predisposing factors, pathogens and outcomes in patients with clinical presumed concomitant microbial and herpes simplex keratitis (HSK) at Sydney Eye Hospital, Australia over a 5-year period. SUBJECTS/METHODS: A retrospective case review was conducted. Patients with clinical presumed concomitant microbial and HSK from 2012 to 2016 were identified from pathology and hospital coding databases. Data were extracted from the medical records. VA was converted to the logarithm of the minimum angle of resolution (logMAR). 'Poor' outcome was defined as final VA worse than 6/60, or decrease in VA during treatment, or presence of complication, or needed surgical intervention. RESULTS: 126 episodes in 121 patients were included; median age 70 years (range 18-96); 56% male. Predisposing factors included blepharitis 20/126 (16%) cases, and corneal transplantation 19 (15%). Forty-six (37%) cases had prior HSK. Coagulase-negative staphylococci 51/116 (44%), Staphylococcus aureus 11 (9%), and Pseudomonas aeruginosa 11 (9%) were the most common isolates. The median VA at initial visit was 1.7 logMAR (range 0.04-2.7) and at final visit, 0.98 logMAR (range 0-2.7) (P < 0.05). Complications occurred in 70 episodes: persistent epithelial defect in 38 (30%); intraocular pressure elevation in 15 (12%), and corneal perforation in 12 (10%). 'Poor' outcome was recorded in 46/75 (61%) episodes. CONCLUSIONS: Patients with clinical presumed concomitant microbial and HSK face significant ocular morbidity and poor visual outcome. In our setting, previous HSK, corneal and ocular surface disease, were common predisposing factors and Gram-positive bacteria were the most commonly associated organisms.

Clinical outcomes of herpes simplex keratitis: Two-year experience from a quaternary eye care centre in Sydney, Australia.

PURPOSE: To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia. METHODS: A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis. RESULTS: Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500 mg to 1 g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n = 114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8 days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n = 8) and secondary bacterial keratitis (n = 6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6 months. CONCLUSIONS: Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes.

Late onset of microbial keratitis after laser in situ keratomileusis surgery: case series.

PURPOSE: To report predisposing factors, clinical features, microbiology spectrum, antibiotic resistance, antimicrobial therapy, and outcomes of patients with a previous laser in situ keratomileusis (LASIK) surgery and diagnosed with presumed microbial keratitis. SETTING: Sydney Eye Hospital, Sydney, New South Wales, Australia. DESIGN: Retrospective case review. METHODS: Patients were identified from pathology and hospital coding data from 2012 to 2016. Inclusion criteria were all patients with a previous LASIK surgery, a presumed diagnosis of microbial keratitis, and a corneal scrape performed and aged older than 18 years. Demographics, clinical details, and outcomes were collated from the medical records. RESULTS: Sixteen patients were included, with median age of 41.5 years (range 22 to 85 years) and 56.2% of women. The median time between LASIK procedure and microbial keratitis presentation was 38.3 months (interquartile range 6.7 to 77.45 months). Cultures were positive for bacteria in 12 (75%) of 16 scrapes. Of the bacterial isolates, 12 (85.7%) were gram-positive and 2 (14.3%) gram-negative. Sensitivity profiles for the isolated bacteria were similar between fortified antibiotics (cefalotin and gentamicin) and commercial products (chloramphenicol and ofloxacin). Complications included the need for tectonic grafts, nonhealing epithelial defects, thinning, and neovascularization. CONCLUSIONS: Late onset of keratitis after LASIK can occur with no positive cultures for nontuberculous mycobacteria, no interface involvement, and no other usual features reported in case series of infectious keratitis in LASIK patients. It has a similar clinical course to non-LASIK keratitis, such that the surgery may not have been a risk factor for infection.

Microbial Keratitis After Corneal Collagen Cross-Linking for Corneal Ectasia.

PURPOSE: The aim of this study was to report the clinical profile and microbiological of patients with microbial keratitis post accelerated corneal collagen cross-linking (CXL). METHODS: A retrospective case series of all patients diagnosed with microbial keratitis post-CXL who attended the Sydney Eye Hospital, Australia from January 1, 2012 to December 31, 2019 were included. Patients were identified from hospital coding and pathology data. Data were extracted from patients' medical records. RESULTS: Eleven eyes from 10 patients with a mean age of 29 ±â€Š11 years (range 16-48) were included. The median time of infection after CXL surgery was 4 days [interquartile range (IQR) 3-83]. Median initial and final Visual acuity at presentation were 1.3 logMAR (IQR 1-2.0) and 0.8 logMAR (IQR 0.6-1.2), respectively. The culture positivity rate was 92%, identifying 13 isolates, predominately made up of coagulase-negative Staphylococcus (n = 6, 50%) and Staphylococcus aureus (n = 3, 25%). The median epithelial healing time was 30 days (IQR 15-53). CONCLUSIONS: Post-CXL microbial keratitis was predominately associated with gram-positive bacteria and in some cases delayed epithelialization. Microbial keratitis post-CXL may lead to moderate to poor patient outcomes.

Bacterial Ocular Surveillance System (BOSS) Sydney, Australia 2017-2018.

ABSTRACT: This study investigated antimicrobial resistance (AMR) profiles from a cohort of patients with bacterial keratitis treated at Sydney Eye Hospital, 1 January 2017 - 31 December 2018. These AMR profiles were analysed in the context of the current Australian empiric regimens for topical therapy: ciprofloxacin/ofloxacin monotherapy versus combination therapy of cefalotin/cephazolin plus gentamicin. At our Centre, combinations of (i) chloramphenicol plus gentamicin and (ii) chloramphenicol plus ciprofloxacin are alternatively used, so were also analysed. Three hundred and seventy-four isolates were cultured prospectively: 280/374 (75%) were gram positive, and 94/374 (25%) were gram negative. Coagulase-negative staphylococci comprised 173/374 (46%). Isolates included Staphylococcus aureus (n = 43/374) 11%; Streptococcus pneumoniae (n = 14/374) 3.7%; and Pseudomonas aeruginosa (n = 50/374) 13%. Statistical comparison was performed. There was no significant difference between cover provided either of the current Australian recommendations: ciprofloxacin/ofloxacin vs cefalotin/cephazolin plus gentamicin (5.3% vs 4.8%, respectively; p = 0.655). However, the combination of chloramphenicol plus an anti-pseudomonal agent (ciprofloxacin/ofloxacin or gentamicin) had significantly improved cover. Chloramphenicol plus gentamicin was superior to ciprofloxacin/ofloxacin (1.9% vs 5.3% resistance respectively; p = 0.007), and cefalotin/cephazolin plus gentamicin (1.9% vs 4.8%; p = 0.005). Chloramphenicol plus ciprofloxacin was superior to ciprofloxacin/ofloxacin monotherapy (1.3% vs 5.3%; p ≤ 0.001), and to cefalotin/cephazolin plus gentamicin (1.3% vs 4.8%; p = 0.003). Chloramphenicol plus gentamicin versus chloramphenicol plus ciprofloxacin/ofloxacin were equivalent (p = 0.48). There was no demonstrated in vitro superiority of either the current empiric antibiotic regimens. For our setting, for bacterial keratitis, chloramphenicol in combination offered superior in vitro cover. Broadened surveillance for ocular AMR is urgently needed across jurisdictions.

Topical Steroids as Adjunctive Therapy for Bacterial Keratitis: Evidence From a Retrospective Case Series of 313 Cases.

PURPOSE: The aim of this study was to report topical steroid usage in bacterial keratitis and analyze the effects of steroids on patients' outcomes to the main causative organisms. DESIGN: A retrospective case-series. METHODS: This study included all patients with corneal scrape positive bacterial keratitis from January 2012 to December 2016 at the Sydney Eye Hospital, Sydney, Australia. Cases were identified from pathology results and hospital coding, and data collected from medical records. RESULTS: A total of 313 eyes from 308 patients with a mean age of 51 years [interquartile range (IQR) 36-72] were included. Of these patients, 192 (61%) were treated with topical steroids. High-dose steroids were prescribed in 22 (11%) cases, regular-dose in 88 (46%), and low-dose in 82 (43%). The median time until the implementation of steroid use was 4 days (IQR 3-7). Patients prescribed with topical steroids had significantly longer healing times than the "no steroid" group (11 vs 6.5, P < 0.001). Patients with Pseudomonas aeruginosa keratitis and topical steroid use had worse clinical outcomes, with a higher proportion having longer healing times (P = 0.04) and corneal scarring (P = 0.02). CONCLUSIONS: Adjuvant topical steroid therapy did not affect visual acuity, patient outcomes or the rate of adverse effects but may delay epithelial healing in bacterial keratitis in these patients. Topical steroids may have a differential effect depending on the specific causative organisms; however, a clinical trial is needed to assess this.

Pediatric Microbial Keratitis: Experience From Tertiary Referral Centers in New South Wales, Australia.

AIMS: The purpose of this study was to report the epidemiology, etiology, microbiologic profile and management of pediatric microbial keratitis in a quaternary and 3 tertiary ophthalmic referral centers across Sydney, New South Wales, Australia. METHODS: This is a retrospective cohort study of patients ≤ 18 years of age with a clinical diagnosis of microbial keratitis presenting between 1 January 2010 and 31 December 2016 identified from hospital coding and pathology databases. Data were extracted from the medical records. Epidemiology, predisposing factors, referral patterns, microbial profile and treatment outcomes were analyzed. RESULTS: Eighty eyes from 80 pediatric patients with microbial keratitis were included in the study (10% had bilateral disease). The mean age was 11 ± 5.3 years (range 0-18 years), and 44 were male (55%). Thirty-six percent of patients had ocular and 13.5% systemic comorbidities. The most common risk factor overall was contact lens wear in 26%, trauma (24%), and external lid and eye disease (20%). Overall, 74 organisms were identified, and of those, the most common isolates were Gram-positive organism. Antimicrobial resistance to common antibiotics was low across all isolates. Visual acuity following treatment was worse than 6/60 for 7 patients (11.3%%), 6/15-6/60 for 15 patients (24.2%) and better than 6/12 for 40 patients (64.5%). Preexisting corneal disease and delay of presentation were associated with worse visual prognosis. Serious complications were noted in 16 (21.3%) of patients. CONCLUSIONS: Contact lens wear, trauma and existing ocular disease remain the most significant risk factors in the pediatric population. Preexisting corneal disease and delay in presentation were associated with poor visual acuity. The majority of patients have a good visual outcome although serious complications are not uncommon and may cause lifelong visual disability.