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.

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.

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.

Microbial keratitis in Sydney, Australia: risk factors, patient outcomes, and seasonal variation.

PURPOSE: To provide recent data on patient demographics, clinical profile and outcomes of patients with microbial keratitis over a 5-year period at the Sydney Eye Hospital, and to identify seasonal variations of the main causative organisms. METHOD: A retrospective study of patients with a clinical diagnosis of microbial keratitis and corneal scrape performed between 1 January 2012 and 31 December 2016. Clinical information was gathered from medical records and pathology data. RESULTS: One thousand fifty-two eyes from 979 patients with a mean age of 54.7 ± 21.5 years (range 18-100 years) were included. The majority of cases were bacterial (65%) followed by polymicrobial (2.4%), fungi (2.3%), and culture-negative (31%). Common risk factors for microbial keratitis were contact lens wear (63%) and previous topical steroid use (24%). Factors significantly associated with poor patient outcomes in the multivariate model were age, visual acuity, and epithelial defect size (p < 0.05). Patients with fungal or polymicrobial keratitis presented with worse clinical features at initial and final presentation (p < 0.05). There was a significant variation in the occurrence of Pseudomonas aeruginosa (p = 0.018) and fungal keratitis (predominately made up of Candida and Fusarium species) (p = 0.056) in the hottest seasons. CONCLUSION: Poorer outcomes are more likely to be seen in older patients and those presenting with poor visual acuity and large epithelial defects at the initial presentation.

The clinical and microbiological features and outcomes of fungal keratitis over 9 years in Sydney, Australia.

To describe the clinical features, management and outcomes in patients with fungal keratitis at the Sydney Eye Hospital, Australia, over a 9-year period to guide appropriate initial therapy. A retrospective case review was conducted. Patients diagnosed with fungal keratitis from 1 January 2009 to 31 December 2017 were identified from hospital coding and pathology databases. Data were extracted from the medical records. A total of 55 episodes from 51 patients were included. Mean age was 60 ± 20 years (range: 19-91 years), and 33 were male. The fungal species was not identified in two patients. Predisposing factors included ocular surface disease in 17 eyes (32%); corneal disease, 15 (28%); corneal trauma, 12 (23%); and contact lens wear, 13 (24.5%). Fusarium spp. (15, 27%) and Candida parapsilosis (10, 18%) were the most common isolates. The median visual acuity at presentation was 1.3 logMAR (range: 0 to 3) and after treatment 0.7 logMAR (range: -0.02 to 3) (P = .008). Despite medical therapy, most commonly with natamycin and topical and oral voriconazole, surgical intervention was required in 21 eyes (40%); including antifungal injections in 9 (16%); corneal transplantation, 16 (30%); evisceration, 2 (4%); and enucleation, 1 (2%). A poor visual outcome was recorded in 27 of 43 (63%) patients. Fungal keratitis remains a cause of significant ocular morbidity; the majority of patients face a poor outcome despite intense medical and at times surgical treatment. In our setting, fungal keratitis was more commonly associated with corneal or ocular surface disease.

Antimicrobial resistance trends in bacterial keratitis over 5 years in Sydney, Australia.

IMPORTANCE: Antimicrobial resistance (AMR) patterns in bacterial keratitis may fluctuate in a geographic location over time. BACKGROUND: To investigate any change in AMR patterns in Sydney, Australia. DESIGN: Retrospective case series. PARTICIPANTS: All patients with microbial keratitis who underwent a corneal scrape and culture from 2012 to 2016 at the Sydney Eye Hospital. METHODS: Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry identified organisms. The Calibrated Dichotomous Susceptibility method determined antibiotic susceptibilities. MAIN OUTCOME MEASURES: Isolated organisms and antibiotic susceptibilities. RESULTS: There were 1084 corneal scrapes from 957 patients. The mean age was 54 years (range 18-100) and 52% were male. Cultures were positive in 711 of 1084 scrapes (66%), with 884 organisms identified. Of the bacteria isolated, 685 of 884 (78%) were Gram-positive and 199 of 884 (22%) were Gram-negative. Overall, the most common bacteria were coagulase-negative Staphylococci (CoNS) (405/884, 46%). Methicillin-resistance was detected in 7% of Staphylococcus aureus isolates (7/103). Methicillin-resistance in CoNS (ie, also cefalotin resistance) was reported in 19% of isolates and ciprofloxacin 8%. For methicillin-sensitive S aureus (MSSA), 5% of isolates were resistant to ciprofloxacin. For Corynebacterium spp., 34% of isolates were resistant to chloramphenicol and 9% to ciprofloxacin. The most common Gram-negative bacteria was Pseudomonas aeruginosa (109/199, 55%). One case was resistant to ciprofloxacin. CONCLUSIONS AND RELEVANCE: Coagulase-negative staphylococcal species were the most frequently suspected of causing bacterial keratitis. Increased resistance to cefalotin was identified for CoNS and to ciprofloxacin for Corynebacterium spp., MSSA and P aeruginosa compared to a previous study in Sydney in 2002 to 2003.

A low literacy targeted talking book about radiation therapy for cancer: development and acceptability.

PURPOSE: To develop a low literacy talking book (written book with accompanying audio-recording) about radiation therapy and explore its acceptability with patients and caregivers. METHOD: The talking book was developed iteratively using low literacy design principles and a multidisciplinary committee comprising consumers and experts in radiation oncology, nursing, behavioural sciences, and linguistics. It contained illustrations, photos, and information on: treatment planning, daily treatment, side effects, psychosocial health, and a glossary of medical terms. Semi-structured interviews were conducted with patients who self-reported low functional health literacy and caregivers to explore their views on the resource. Thematic analysis using a framework approach informed the analysis. RESULTS: Participants were very satisfied with the content, illustrations, and language in the resource. Most were unfamiliar with the term 'talking book', but liked the option of different media (text and audio). The resource was seen as facilitating communication with the cancer care team by prompting question-asking and equipping patients and their families with knowledge to communicate confidently. CONCLUSIONS: The low literacy talking book was well accepted by patients and their caregivers. The next step is to examine the effect of the resource on patients' knowledge, anxiety, concerns, and communication with the cancer care team.

Keratitis antimicrobial resistance surveillance program, Sydney, Australia: 2016 Annual Report.

IMPORTANCE: Antimicrobial resistance data from bacterial keratitis in Australia are lacking. BACKGROUND: Antimicrobial resistance is a global health threat. Bacterial keratitis is an ophthalmic emergency requiring immediate and effective treatment. DESIGN: Retrospective cohort study of bacterial isolates and antibiotic susceptibility profiles at a quaternary hospital in Sydney, Australia. PARTICIPANTS: Two hundred and twenty-four corneal scrapes from patients from January 1 to December 31, 2016. METHODS: Matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry identified bacteria. The Calibrated Dichotomous Sensitivity (CDS) method determined antibiotic susceptibilities. MAIN OUTCOME MEASURES: Isolated organisms and antibiotic susceptibilities. RESULTS: One hundred and sixty-eight scrapes of 224 (75%) were culture positive. One hundred and thirty-one patients had a single organism isolated and 21 had mixed bacterial growth. Of the 157 organisms isolated, 131 (83%) were Gram-positive and 27 (17%) Gram-negative. Of the Gram-positive organisms, 75 (57%) were coagulase-negative Staphylococci (CoNS), 15 (11%) Staphylococcus aureus (including one methicillin-resistant Staphylococcus aureus [MRSA]) and 8 (6%) Corynebacterium spp. Of the Gram-negative organisms, 15 (58%) were Pseudomonas aeruginosa. With methicillin-sensitive Staphylococcus aureus (MSSA) resistance to chloramphenicol was 21%, ciprofloxacin 7% and gentamicin 7%. With CoNS resistance to cefalotin was 9%, gentamicin 9% and ciprofloxacin 9%. With Corynebacterium spp. resistance was 40% to cefalotin, chloramphenicol 25% and ciprofloxacin 14%. CONCLUSIONS AND RELEVANCE: Staphyloccocus spp. and Pseudomonas spp. were the most common microorganisms isolated. There was low resistance to cefalotin and ciprofloxacin for these isolates. More than 90% of these would be covered by current therapeutic recommendations for empiric therapy in Australia.

Clinical translation of recommendations from randomized trials for management of herpes simplex virus keratitis.

IMPORTANCE: To standardize initial anti-viral therapy for herpes simplex keratitis (HSK). BACKGROUND: To determine prescribing trends for the management of HSK and compare the trends to available clinical trial evidence. DESIGN: Retrospective review of patients at the Sydney Eye Hospital, Australia. PARTICIPANTS: Three hundred and one eyes of 296 patients prescribed anti-virals for HSK aged 18 years and above, from 1 January 2012 to 31 December 2013. METHODS: Patients were identified from viral swab results, pharmacy records and International Classification of Diseases 10 (ICD-10) coding data. MAIN OUTCOME MEASURE: Initial anti-viral therapy. RESULTS: Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 256 (85%) and 45 (15%) eyes, respectively. Overall, anti-virals prescribed included valaciclovir 500-1000 mg 1-3 times daily, aciclovir 200-400 mg 1-5 times daily, topical aciclovir 2-5 times daily and topical trifluorothymidine two hourly or as needed daily or combined oral and topical anti-virals. Indication and dose of prescribed anti-virals aligned with clinical evidence in 125 of 141 eyes (89%) with epithelial HSK, 2 of 22 eyes (9%) with stromal without ulceration HSK, 6 of 18 (28%) eyes with endothelial HSK and 31 of 45 (69%) eyes with HSK prophylaxis. Overall, 164 eyes (54%) received 'evidence-based' anti-viral therapy. CONCLUSIONS AND RELEVANCE: Prescribing patterns for anti-viral therapy to treat and prevent recurrence of HSK were diverse. Local guidelines are needed to standardize the indications and dose of initial anti-viral therapy for HSK. Implementation of these guidelines will likely improve patient care and rationalize the use of health resources.

Experiences of vision impairment in Papua New Guinea: implications for blindness prevention programs.

INTRODUCTION: A person's capability to access services and achieve good eye health is influenced by their behaviours, perceptions, beliefs and experiences. As evidence from Papua New Guinea (PNG) about people's lived experience with vision impairment is limited, the purpose of the present study was to better understand the beliefs, perceptions and emotional responses to vision impairment in PNG. METHODS: A qualitative study, using both purposive and convenience sampling, was undertaken to explore common beliefs and perceptions about vision impairment, as well as the emotional responses to vision impairment. In-depth interviews were undertaken with 51 adults from five provinces representing culturally and geographically diverse regions of PNG. Grounded theory was used to elicit key themes from interview data. RESULTS: Participants described activities of everyday life impacted by vision impairment and the related worry, sadness and social exclusion. Common beliefs about the causes of vision impairment were environmental stressors (sun, dust, dirt and smoke), ageing and sorcery. CONCLUSIONS: Findings provide insight into the unique social context in PNG and identify a number of programmatic and policy implications, such as the need for preventative eye health information and services, addressing persisting beliefs in sorcery when developing health information packages, and the importance of coordinating with counselling and well-being services for people experiencing vision impairment.

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.

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.

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.