Next-Generation Sequencing of the Ocular Surface Microbiome: In Health, Contact Lens Wear, Diabetes, Trachoma, and Dry Eye.

OBJECTIVES: To assess publications examining the occurrence, composition, and clinical significance of a microbiome at the ocular surface. METHODS: MEDLINE, EMBASE, and Google Scholar were searched. Reference lists of included articles were also searched for relevant citations. All publications up to June 1, 2019, were analyzed. RESULTS: Eleven articles and 1 abstract were included, analyzing 661 patients. Articles generally report bacteria to the genus level. The presence of DNA associated with diverse bacterial species was reported including pathogenic species, such as Pseudomonas and Neisseria. Bacterial DNA that makes up the microbiome, such as Acinetobacter, Actinomyces, Aquabacterium, Bradyrhizobium, Corynebacterium, Sphingomonas, Staphylococcus, and Streptococcus, in other parts of the body was found. The putative ocular microbiome is consistent between right and left eyes and is affected by contact lens use (higher Pseudomonas levels) and blepharitis (higher Staphylococcus levels). CONCLUSIONS: There is a significant likelihood that there is at least a transitory ocular surface microbiome, with Acinetobacter, Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus detected in at least 7 of 11 studies. However, further investigation attempting to control for environmental and methodological contaminants (Aquabacterium and Bradyrhizobium are commonly identified as contaminants in DNA extraction kits) is required. Bacteria, such as Propionibacterium, Staphylococcus, and Streptococcus, capable of causing sight-threatening infections may reside on a healthy ocular surface. With greater understanding, we can establish whether elements of the ocular surface microbiome are harmful or protective (despite their small quantities); furthermore, new therapeutic agents can be identified to treat and prevent ocular surface infection and inflammation.

Managing Post Keratoplasty Astigmatism.

Corneal transplantation, when used in the correct setting, can significantly improve visual acuity and therefore quality of life. One of the barriers to good vision following keratoplasty is residual post operative surgical astigmatism. Following a thorough literature search, we present the different options available to readers, with regards to how post-operative astigmatism can be approached and managed in order to improve vision. We present available data from the literature, which in some areas are scarce, with a view to collating all of this information in one place, allowing comparison between different modalities of treatment.

Impact of First Healthcare Provider on Acanthamoeba Keratitis Course: How to Overcome Poor Prognosis in Acanthamoeba Keratitis Treatment? A Single Tertiary Center, Observational Study.

Background: To assess the difference in course and final visual outcome of Acanthamoeba keratitis (AK) patients based on the first healthcare provider (HCP) seen. Methods: Retrospective observational cohort study of AK patients admitted to the Manchester Royal Eye Hospital between 2003 and 2017. HCPs were grouped (Group 1: Optometrists, Opticians; Group 2: General Practitioners (GPs); Group 3: Ophthalmologists) and the data analyzed on demographics, risk factors, clinical history, clinical features, and Acanthamoeba subspecies. Results: Forty-one patients with unilateral culture-proven AK were included. Median time to consultation with first HCP was 7 days (IQR 4-14 days), while mean time to the correct diagnosis of AK was 15 days (IQR 7-29 days). Patients saw an optician, optometrist or ophthalmologists significantly earlier than GPs (median 4 days, vs 15 or 5 days, respectively, p = 0.04). Bacterial keratitis was the most common initial clinical diagnosis (43%). The shortest time to making the AK diagnosis (median 11 days) and the highest rate of initiating AK treatment started at the first visit (38%) were both in the ophthalmologists' group. No significant differences were observed in initial and final visual acuity between HCP groups (p = 0.36). Conclusion: AK patients often seek ocular help earlier from optometrists and opticians than medical doctors. Final clinical outcomes did not significantly differ based on the first HCP seen, but ophthalmologists were more likely to make the diagnosis of AK and initiate anti-amoebal therapy faster than other HCPs. Greater education and collaboration between ophthalmologists and other HCPs to increase awareness of AK are needed.

Impact of the COVID-19 Pandemic on the Incidence and Characteristics of Culture-Positive Microbial Keratitis at a Tertiary Eye Hospital in the UK.

Purpose: The COVID-19 pandemic has led to drastic changes to the daily lives of those living in the United Kingdom. We hypothesized that the effect of the imposed lockdown on both behaviour and social interaction has the potential to influence the characteristics of microbial keratitis presenting locally to Manchester Royal Eye Hospital - a major tertiary eye centre in the UK. Methods: We conducted a retrospective case-note review of all positive corneal scrape cultures identified by our local microbiology laboratory during the year since the announcement of lockdown measures in the UK (23 March 2020 to 23 March 2021). Culture results were compared with previously collated, published "baseline" data from prior to the onset of the COVID-19 pandemic (2004-2019). Statistical analysis was undertaken, predominantly looking at the incidence of microbial keratitis and the variety of cultured pathogens. Results: A total of 6243 corneal scrape results were reviewed. Comparison of data between the COVID-19 pandemic and subsequent lockdown did not show a significant change in the incidence of culture-positive microbial keratitis: mean annual positive samples during 2004-2019 were 128 (35%) vs 91 (29%) during lockdown (P=0.096). No statistically significant shifts in the incidence of organism subtypes - fungi, acanthamoeba, Gram-positive bacteria, or Gram negative bacteria - were identified (P=0.196, 1, 0.366, and 0.087, respectively). Conclusion: Contrary to our hypothesis, our results suggest that the COVID-19 pandemic did not alter the incidence or characteristics of microbial keratitis presenting to Manchester Royal Eye Hospital in the year following the implementation of lockdown measures in the UK.

Current Perspectives on Corneal Transplantation (Part 2).

Disease of the cornea is the third leading cause of blindness worldwide. Corneal graft surgery is one of the most successful forms of solid organ transplantations in humans, with ever increasing developments in surgical technique. To date, approximately 4504 corneal transplants are performed in the UK each year. While full thickness transplantation was the most commonly performed keratoplasty over the last few decades, selective lamellar transplantation of the diseased layers of the cornea has been universally adopted. This comprehensive review aims to provide an updated synthesis on different types of corneal transplantations, their treatment outcomes, and the associated complications of each procedure both in adult and pediatric populations. In addition, we also present an up-to-date summary of the emerging therapeutic approaches that have the potential to reduce the demand for donor-dependent keratoplasty.

Current Perspectives on Corneal Transplantation.

Disease of the cornea is the third leading cause of blindness worldwide. Corneal graft surgery is one of the most successful forms of solid organ transplantations in humans, with ever-increasing developments in surgical technique. To date, approximately 4504 corneal transplants are performed in the United Kingdom each year. While full thickness transplantation was the most commonly performed keratoplasty over the last few decades, selective lamellar transplantation of the diseased layers of the cornea has been universally adopted. This comprehensive review aims to provide an updated synthesis on different types of corneal transplantations, their treatment outcomes, and the associated complications of each procedure in both adult and paediatric population. In addition, we also present an up-to-date summary of the emerging therapeutic approaches that have the potential to reduce the demand for donor-dependent keratoplasty.

Surgical advancement in glaucoma during the past 10 years.

Recent years have seen a trend towards change in glaucoma treatment. In addition to classic trabeculectomy, implant surgeries such as those based on the Baerveldt, Ahmed and Molteno devices are increasingly performed as a primary procedure. This is doubtless partly due to the fact that surgeons have become more comfortable with the use of tube shunts and their postoperative management. The aim of this article is to present the currently available evidence on glaucoma surgery in a succinct format, to enable the best possible decisions to be made for patients.

Amniotic Membrane Transplantation in Ophthalmology: An Updated Perspective.

AIM: The aim of this paper is to provide a succinct literature review of the different clinical applications for AMT usage in an ophthalmic setting, ranging from commonly used applications to less mainstream approaches. The hope is that this review enables the reader to have a better understanding of the biological properties of amnion as well as the indications and scenarios in which AMT can be used, whilst presenting relevant evidence from within the literature which may be of interest. We also provide an update on the methods of preservation of amniotic membrane and the application methodologies. METHODS: Literature search. A PubMed search was performed using the search terms "amniotic membrane transplant", "amnion AND cornea", amnion AND ophthalmology", "amnion AND ocular surface" and "Amnion AND eye". A full review of the literature using the PubMed database was conducted up until 01/05/20. The articles used were written in English, with all articles accessed in full. Both review articles and original articles were used for this review. All full publications related to ophthalmology were considered.

Trabeculectomy Training: Review of Current Teaching Strategies.

The aim of this paper is to introduce readers to potential strategies available for teaching trabeculectomy surgery. Trainee surgical outcomes and various surgical simulation techniques are discussed, with suggestions on how to measure progress and consideration of relevant educational theories.

Visual and anatomical outcomes of central serous chorioretinopathy patients presenting to a tertiary unit: a prospective analysis.

AIM: The aim of this study was to prospectively define the characteristics and outcomes of a cohort of central serous chorioretinopathy patients using optical coherence tomography imaging to determine anatomical disease resolution. Much of the literature available on the characteristics of central serous chorioretinopathy patients pre date the advent of OCT imaging, with conclusive epidemiological evidence being scarce. We describe a cohort of patients presenting to a large centre over the course of a year. METHODS: Prospective data collection was undertaken for all patients diagnosed with central serous chorioretinopathy at our unit over the course of 1 year. All patients underwent thorough history taking and optical coherence tomography imaging. RESULTS: In total, 59 eyes from 51 patients were diagnosed with central serous chorioretinopathy between April 2017 and April 2018; 23 (45.1%) patients had optical coherence tomography evidence of complete anatomical resolution within a year, with three (5.88%) patients suffering a worse visual acuity compared with that at presentation at 1-year end point; and three patients developed secondary choroidal neovascular membranes. CONCLUSION: Our study reports much-needed prospective outcomes of patients with central serous chorioretinopathy, which helps to guide clinicians when deciding treatment strategies, as well as better informing patients of their prognosis for visual improvement.

Microbial Keratitis in Corneal Transplants: A 12-Year Analysis.

PURPOSE: To investigate the frequencies, trends, and in vitro drug susceptibilities of the causative pathogens in corneal transplant microbial infections in Manchester Royal Eye Hospital. METHODS: Corneal scrape results recorded by the microbiology service between 2004 and 2015 were extracted from an established database. This microbiological data was matched with a separate database of all corneal transplant procedures performed in our centre over this time period. Patient records were examined to collect specific patient data and to confirm the diagnosis of microbial keratitis. RESULTS: A total of 1508 grafts had been performed at our centre in this period. 72 episodes of graft microbial keratitis were identified from 66 eyes that had undergone keratoplasty procedures. Mean age was 56, and 51% of subjects were male. Ninety-three percent of microbial keratitis episodes occurred in penetrating keratoplasty procedures and 6% in deep anterior lamellar keratoplasty procedures. No endothelial grafts presented with infections throughout this time period. Of the 79 organisms identified, 73% were gram positive, 23% gram negative and 4% fungi. With regard to gram-positive organisms, vancomycin and gentamicin showed 100% and 91% susceptibility, respectively. Ofloxacin had a resistance rate of 13.7%. In terms of gram-negative organisms, gentamicin and chloramphenicol showed 100% sensitivity, with cefuroxime showing 69%. Resistance rates were less than 15% in all tested gram-negative antimicrobials. CONCLUSION: This paper describes the largest collection of corneal transplant infections identified within the UK. This finding may aid clinicians in predicting possible causative organisms for microbial keratitis and aid antibiotic choice.

Brittle cornea syndrome: current perspectives.

Brittle cornea syndrome (BCS) is a rare autosomal recessive connective tissue disorder characterised by severe corneal thinning, with the major ocular risk being spontaneous ocular perforation due to progressive stromal thinning and ectasia. It is a complex condition with limited treatment options. The purpose of this review is to highlight the difficulties associated with the condition and examine the available published evidence with regards to management.

Clinical Effectiveness of Intravitreal Fluocinolone Acetonide (FAc) (ILUVIEN™) in Patients with Diabetic Macular Oedema (DMO) Refractory to Prior Therapy: The Manchester Experience.

INTRODUCTION: Diabetic macular oedema (DMO) remains a significant cause of sight loss in the UK. Despite macular laser and anti-VEGF agents, a large proportion of patients remain with persistent DMO. We present our results of using 0.19 mg fluocinolone acetonide (FAc) intravitreal implant in this cohort with up to 3 years of follow-up. METHODS: This is a single-centre retrospective review of patients treated with FAc implant for refractory DMO. The primary efficacy end point was visual acuity and secondary efficacy end point was central retinal thickness (CRT) on OCT. A primary safety end point was a rise in IOP requiring treatment. RESULTS: Twenty-one eyes were identified with an average follow-up of 27 months (6-36 months). Visual acuity change from baseline was - 0.1 ETDRS letters at year 1 (n = 13), 8.1 letters at year 2 (n = 13) and 10.7 letters at year 3 (n = 10). CRT improved by - 132.1 µm at year 1 (n = 15), - 172.8 µm at year 2 (n = 13) and - 157.8 µm at year 3 (n = 10). Five eyes (24%) required further anti-VEGF during follow-up and two (9.5%) required further focal laser. IOP rise requiring treatment was noted in eight eyes (38%). Seven were steroid induced. One was caused by rubeotic glaucoma. Six (75%) were managed medically and the remaining two also required surgery. CONCLUSION: This data add to the limited real-world data on FAc in DMO with 3 years of follow-up. Vision and macular architectures both improved at varying rates over 3 years in patients with refractory DMO. IOP rise is a risk but, in the majority, it can be managed medically.

Primary glaucoma surgery in Fuchs' heterochromic uveitis: a comparison of trabeculectomy versus deep sclerectomy.

BACKGROUND: Deep sclerectomy offers the potential advantage of less postoperative inflammation and better survival in Fuchs' patients. The aim of this study was to compare survival and safety profiles of Fuchs' heterochromic uveitis patients undergoing trabeculectomy or deep sclerectomy. METHODS: A retrospective study was conducted of two separate cohorts who had undergone either trabeculectomy or deep sclerectomy. Patient demographics, best-corrected visual acuity, intraocular pressure, antimetabolite used, postoperative complications and subsequent procedures were analysed. RESULTS: In total, 13 trabeculectomy patients and 14 deep sclerectomy patients were included. Mean preoperative intraocular pressure was similar at 30.1 mmHg in the trabeculectomy group and 35.9 mmHg in the deep sclerectomy group, with no significant difference between the two (p = 0.22). Kaplan-Meier survival outcomes for success at <22 mmHg and <19 mmHg showed no significant differences between the groups and this was also the case for intraocular pressure at 3 years (analysis of variance; p = 0.47). CONCLUSION: Both procedures appear to have similar efficacy and safety profiles, suggesting that both are effective.

Determining the needs of ophthalmic trainees entering into specialist training and how they can be met.

Problem: Starting ophthalmic specialty training can be daunting as new basic clinical examination and surgical skills must be acquired before meaningful assessment of patients can begin. No formal clinical induction currently exists with the aim to teach clinical and practical skills to new starters. Aim and objectives: To determine the experience and needs of ophthalmic trainees entering into specialist training. Using this information we developed and implemented a clinical skills training programme for Ophthalmology ST1s. Intervention: Using SMART objectives, PDSA cycles and Chartered Institute of Personnel Development guidance we implemented a clinical skills induction week. Pre-course skills evaluation took place in the form of a questionnaire in order to tailor the course content to the skill level of the group. Course material was made and simulation techniques devised for teaching practical skills. Qualitative data was collected via a pre- and post-course questionnaire. Outcome: All 9 participants rated the course as "extremely useful" it increased their confidence in terms of commencing clinical ophthalmology. 100% of participants felt that this course should be delivered to new ST1s. All participants reported improved confidence in managing ophthalmic emergencies and their clinical skills technique. Lessons learned: A sustainable induction programme was implemented tailored to the prior experience and skills of ST1 trainees. All participants felt it improved their confidence and clinical skills prior to commencing clinical activities. Basic clinical skills can be taught in a cost effective manner early on in postgraduate training.

Gross anterior segment ischaemia following vitreoretinal surgery for sickle-cell retinopathy.

We report the case of a 32-year-old Afrocaribbean man with known stage 3 proliferative sickle-cell retinopathy who presented with a mixed picture of tractional and rhegmatogenous macula off detachment. He underwent left primary 25 g vitrectomy with silicone oil, delamination and endolaser photocoagulation under a general anaesthetic. He, however, presented 48 hours postoperatively with gross anterior segment ischaemia. His pain and ocular signs settled over the course of a few days following administration of supplemental oxygen, oral steroids, analgesia and intravenous hydration. Examination showed resolution of his proptosis and orbital signs as well as anterior segment inflammation. He remains under follow-up.

Iridocorneal endothelial syndrome: clinical perspectives.

This article aims to review the clinical management strategies available for the rare iridocorneal endothelial syndrome. The different clinical variations as well as the imaging techniques available to aid diagnosis are discussed. We then present the evidence available to help the reader to understand how the condition can be managed medically and also the important surgical aspects of treatment. This involves raised intraocular pressure management in addition to the visual management options of partial or full thickness keratoplasty. We hope that this review provides an exhaustive but also succinct review of the literature available on what is a rare and difficult condition to treat.

Clinical Characteristics and Outcomes of Moraxella Keratitis.

PURPOSE: Changing trends of infective keratitis have been identified worldwide. The aim of this study was to define the clinical associations, characteristics, and outcomes of patients with culture-proven Moraxella keratitis from a large tertiary corneal unit in the United Kingdom. METHODS: Patients with confirmed Moraxella isolates presenting between January 2004 and November 2016 were analyzed. Patient-related factors were examined, including patient demographics, date of presentation, clinical presentation, predisposing factors, best-corrected visual acuity (BCVA), treatment plans, and clinical outcomes. RESULTS: Eighty-six patients were identified, of whom 61 (70.9%) had at least one recognized predisposing factor. The median BCVA at presentation was 2.60 logarithm of the minimum angle of resolution (logMAR), which improved to median = 0.60 logMAR at final visit (P < 0.001). Visual improvement of more than 2 Snellen lines was achieved in 60.7% of eyes. A significant relationship (P = 0.003) between final vision and the presence of hypopyon was found, where for a fixed BCVA at presentation those with a hypopyon achieved a better final visual acuity of 0.69 logMAR. CONCLUSIONS: Our study showed that although most patients presented with at least one predisposing factor, some of the more traditionally perceived risk factors may need to be reconsidered. We have shown that with aggressive treatment, favorable visual outcomes can be achieved in most patients. Interestingly, the presence of hypopyon at presentation was linked to a better visual outcome, likely because such patients had more to gain in visual potential.

Association Between Season, Temperature and Causative Organism in Microbial Keratitis in the UK.

PURPOSE: Microbial keratitis (MK) is a major cause of corneal blindness worldwide. Variations in season and temperature can affect MK incidence due to specific causative organisms; however, few studies have examined these factors in the UK. METHODS: Retrospective review of all corneal scrapes from patients with MK presenting to Manchester Royal Eye Hospital, UK, between January 2004 and December 2015. Manchester's monthly temperature data were obtained from Met Office UK. Analysis was performed using logistic regression. RESULTS: From 4229 corneal scrapes, 1539 organisms grew (90.6% bacteria, 7.1% fungi, and 2.3% Acanthamoebae sp.). Gram-positive bacteria grew with increasing temperature [odds ratio (OR) 1.62, 95% CI: 1.11-2.39, P = 0.014], and fungi grew with decreasing temperature (OR 0.29, 95% CI: 0.16-0.51, P < 0.001). Moraxella sp. grew with decreasing temperature (OR 0.91, 95% CI: 0.86-0.96, P = 0.001). Compared with winter, overall culture positivity was significantly less likely in summer (OR 0.57, 95% CI: 0.38-0.87, P = 0.008) and spring (OR 0.65, 95% CI: 0.43-0.99, P = 0.045). Gram-negative bacteria were more likely in summer (OR 1.48, 95% CI: 1.06-2.09, P = 0.022) and autumn (OR 1.75, 95% CI: 1.24-2.47, P = 0.001). Candida sp. were less likely in summer (OR 0.25, 95% CI: 0.07-0.82, P = 0.027) and autumn (OR 0.18, 95% CI: 0.05-0.62, P = 0.009), and Acanthamoeba sp. were less likely in summer (OR 0.39, 95% CI: 0.15-0.92, P = 0.037) and spring (OR 0.26, 95% CI: 0.08-0.69, P = 0.011). CONCLUSIONS: Herein we report variation in the incidence of MK-causing organisms by season and temperature; this finding may aid clinicians in predicting possible causative organisms for MK at differing times of the year.