Diagnostic imaging of retinal astrocytomas: A case-series.

OBJECTIVES: To use multimodal imaging techniques to characterise features of retinal astrocytomas (RA) which would aid practitioners distinguish them from other causes of non-pigmented fundal lesions. METHODS: Retrospective analysis of notes and imaging of 17 patients diagnosed with RA at a single centre between January 2012 and June 2021 was conducted. Demographics, examination findings and imaging including colour fundus photography, optical coherence tomography (OCT), infra-red (IR) and ultrasound (US) were analysed. These were compared to differential diagnoses, including retinoblastomas, amelanotic choroidal melanomas, choroidal metastases and idiopathic scleromas. RESULTS: Fourteen patients (82%; 14/17) had idiopathic RA and three (18%; 3/17) were associated with tuberous sclerosis. Mean age at presentation was 43 years. Twelve patients (71%; 12/17) were asymptomatic. Thirteen (76%; 13/17) had better than 6/12 vision, with 41% (7/17) better than 6/6. All lesions were creamy-white. There were two distinct appearances, seven (39%; 7/18) were poorly-defined translucent retinal elevations and eleven (61%; 11/18) were well-defined solid opaque retinal masses. Six (33%; 6/18) displayed clustered, calcified spherules giving them the pathognomonic 'mulberry-like' appearance. On OCT, all appeared as dome-shaped retinal thickening with disruption of the inner retinal layers and nine (60%; 9/15) had intra-retinal cystic spaces giving a 'moth-eaten' appearance. Mean basal diameter and thickness on OCT was 2.93 mm and 0.86 mm, respectively. High internal reflectivity on US was noted in 92% (11/12). CONCLUSIONS: RAs display characteristic clinical, demographic and imaging features which can aid differentiating them from other non-pigmented fundal lesions. We advise using multiple imaging modalities when diagnosing these lesions.

Impact of fluoroquinolones and aminoglycosides on P. aeruginosa virulence factor production and cytotoxicity.

The opportunistic pathogen Pseudomonas aeruginosa is one of leading causes of disability and mortality worldwide and the world health organisation has listed it with the highest priority for the need of new antimicrobial therapies. P. aeruginosa strains responsible for the poorest clinical outcomes express either ExoS or ExoU, which are injected into target host cells via the type III secretion system (T3SS). ExoS is a bifunctional cytotoxin that promotes intracellular survival of invasive P. aeruginosa by preventing targeting of the bacteria to acidified intracellular compartments. ExoU is a phospholipase which causes destruction of host cell plasma membranes, leading to acute tissue damage and bacterial dissemination. Fluoroquinolones are usually employed as a first line of therapy as they have been shown to be more active against P. aeruginosa in vitrothan other antimicrobial classes. Their overuse over the past decade, however, has resulted in the emergence of antibiotic resistance. In certain clinical situations, aminoglycosides have been shown to be more effective then fluoroquinolones, despite their reduced potency towards P. aeruginosa in vitro. In this study, we evaluated the effects of fluoroquinolones (moxifloxacin and ciprofloxacin) and aminoglycosides (tobramycin and gentamycin) on T3SS expression and toxicity, in corneal epithelial cell infection models. We discovered that tobramycin disrupted T3SS expression and reduced both ExoS and ExoU mediated cytotoxicity, protecting infected HCE-t cells at concentrations below the minimal inhibitory concentration (MIC). The fluoroquinolones moxifloxacin and ciprofloxacin, however, up-regulated the T3SS and did not inhibit and may have increased the cytotoxic effects of ExoS and ExoU.

Potential new fluoroquinolone treatments for suspected bacterial keratitis.

Topical fluoroquinolones (FQs) are an established treatment for suspected microbial keratitis. An increased FQ resistance in some classes of bacterial pathogens is a concern. Some recently developed FQs have an extended spectrum of activity, making them a suitable alternative for topical ophthalmic use. For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and several of the Enterobacteriaceae However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. The purpose of this review is to compare the pharmacokinetics and pharmacodynamics of the FQs licensed for topical ophthalmic use with the same parameters for new generation FQs. We performed a literature review of the FQs approved for topical treatment and the new generation FQs licensed to treat systemic infections. We then compared the minimum inhibitory concentrations (MIC) of bacterial isolates and the published concentrations that FQs achieved in the cornea and aqueous. We also considered the potential suitability of new generation FQs for topical use based on their medicinal properties. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to continue with the prescribed antimicrobial, increase the frequency of application, use a combination of antimicrobials or change treatment.

Corneal Endothelial Cell Loss in Glaucoma and Glaucoma Surgery and the Utility of Management with Descemet Membrane Endothelial Keratoplasty (DMEK).

The corneal endothelium has a crucial role in maintaining a clear and healthy cornea. Corneal endothelial cell loss occurs naturally with age; however, a diagnosis of glaucoma and surgical intervention for glaucoma can exacerbate a decline in cell number and impairment in morphology. In glaucoma, the mechanisms for this are not well understood and this accelerated cell loss can result in corneal decompensation. Given the high prevalence of glaucoma worldwide, this review aims to explore the abnormalities observed in the corneal endothelium in differing glaucoma phenotypes and glaucoma therapies (medical or surgical including with new generation microinvasive glaucoma surgeries). Descemet membrane endothelial keratoplasty (DMEK) is increasingly being used to manage corneal endothelial failure for glaucoma patients and we aim to review the recent literature evaluating the use of this technique in this clinical scenario.

Establishing the influence of case complexity on the order of cataract lists: a cross-sectional survey.

OBJECTIVE: Order of the theatre list and complexity of the cases are important considerations which are known to influence surgical outcomes. This survey aimed to establish their influence on cataract surgery. METHODS AND ANALYSIS: Cataract surgeons ordered five cataract cases according to their surgical preference, first using case notes and second using composite ORs (CORs) for posterior capsule rupture. Descriptive and non-parametric statistics were used to analyse the data. RESULTS: Between 11 June and 14 July 2020, 192 cataract surgeons from 14 countries completed the online survey. Majority of the surgeons (142 vs 50) preferred to choose the order of their list (p<0.01) and to review the case notes prior to the day of surgery (89 vs 53; p=0.04). 39.86% preferred to start with the less risky case and 32.43% reserved the last position on the list for the riskiest case. There was a significant trend to order the list in an ascending level of risk, independent of whether case notes or CORs were used. Additionally, 44.79% of the respondents indicated they would be happy to have their list order planned by an automated program based on their preferred risk score. CONCLUSION: This survey demonstrates that cataract surgeons prefer to choose the order of their theatre list and that the order is dependent on the complexity of cases. There is support among surgeons for automated list ordering based on an objective score for risk stratification, such as a COR.

A pipeline to evaluate inhibitors of the Pseudomonas aeruginosa exotoxin U.

Pseudomonas aeruginosa has recently been highlighted by the World Health Organisation (WHO) as a major threat with high priority for the development of new therapies. In severe P. aeruginosa infections, the phospholipase activity of the type 3 secretion system toxin, ExoU, induces lysis of target host cells and results in the poorest clinical outcomes. We have developed an integrated pipeline to evaluate small molecule inhibitors of ExoU in vitro and in cultured cell models, including a disease-relevant corneal epithelial (HCE-T) scratch and infection model using florescence microscopy and cell viability assays. Compounds Pseudolipasin A, compound A and compound B were effective in vitro inhibitors of ExoU and mitigated P. aeruginosa ExoU-dependent cytotoxicity after infection of HCE-T cells at concentrations as low as 0.5 µM. Addition of the antimicrobial moxifloxacin controlled bacterial load, allowing these assays to be extended from 6 h to 24 h. P. aeruginosa remained cytotoxic to HCE-T cells with moxifloxacin, present at the minimal inhibitory concentration for 24 h, but, when used in combination with either Pseudolipasin A, compound A or compound B, a greater amount of viable cells and scratch healing were observed. Thus, our pipeline provides evidence that ExoU inhibitors could be used in combination with certain antimicrobials as a novel means to treat infections due to ExoU producing P. aeruginosa, as well as the means to identify more potent ExoU inhibitors for future therapeutics.

Influence of Corneal Visualization Scheimpflug Technology Tonometry on Intraocular Pressure.

Purpose: To investigate the effect of Corneal Visualization Scheimpflug Technology tonometry (CST) on intraocular pressure (IOP). Design: Cohort study. Participants: Patients with and without primary open-angle glaucoma (POAG) were included. Methods: Intraocular pressure was measured using the Icare rebound tonometer (ICRT; Icare Finland Oy) and the biomechanically corrected IOP (bIOP) using the CST. Intraocular pressure was measured at baseline with ICRT, followed by a CST measurement in one eye with the fellow eye acting as a control. Icare measurements were repeated at 10 seconds and 1, 2, 4, 8, 15, 30, and 60 minutes in both eyes. The ratio of test eye IOP to fellow eye IOP was used to control for intrasubject variation. Main Outcome Measures: Intraocular pressure change following Corneal Visualization Scheimflug Technology tonometry. Results: Forty participants (mean age, 54.09 ± 20.08 years) were included comprising 20 patients with POAG and 20 patients with no ocular abnormalities other than cataract. Mean central corneal thickness was similar in those without POAG (547.4 ± 55.05 µm) and with POAG (520.22 ± 37.59 µm; P = 0.14). No significant change was found in IOP measured with the ICRT in the fellow eye versus the 1-hour period in either the healthy (P = 0.87) or POAG (P = 0.92) group. Significant changes were found in IOP after CST measurement for both healthy (P < 0.01) and glaucomatous (P < 0.01) eyes. After the CST measurement, the IOP reduced continuously from a mean of 13.75 mmHg to 10.84 mmHg at 4 minutes for healthy eyes and from 13.28 mmHg to 11.11 mmHg at 8 minutes for glaucomatous eyes before approaching (83% for healthy eyes and 92% POAG eyes) the pre-CST measurement at 1 hour. Conclusions: Corneal Visualization Scheimpflug Technology tonometry causes a significant reduction in IOP in both glaucomatous and healthy eyes that lasts for at least 1 hour afterward.

Pseudomonas aeruginosa Toxin ExoU as a Therapeutic Target in the Treatment of Bacterial Infections.

The opportunistic pathogen Pseudomonas aeruginosa employs the type III secretion system (T3SS) and four effector proteins, ExoS, ExoT, ExoU, and ExoY, to disrupt cellular physiology and subvert the host's innate immune response. Of the effector proteins delivered by the T3SS, ExoU is the most toxic. In P. aeruginosa infections, where the ExoU gene is expressed, disease severity is increased with poorer prognoses. This is considered to be due to the rapid and irreversible damage exerted by the phospholipase activity of ExoU, which cannot be halted before conventional antibiotics can successfully eliminate the pathogen. This review will discuss what is currently known about ExoU and explore its potential as a therapeutic target, highlighting some of the small molecule ExoU inhibitors that have been discovered from screening approaches.

Hepatitis B in a vaccinated soldier: a case report.

Assessing for an adequate immunological response to a pre-exposure course of hepatitis B vaccine is not routinely recommended in all vaccinated individuals. Current UK guidelines advise checking hepatitis B surface antibody titres only in those considered at high occupational risk such as healthcare and laboratory workers. We present a case of an infantry soldier who developed acute hepatitis B despite having a complete course of hepatitis B vaccinations. This case emphasises that hepatitis B is still an important differential diagnosis for all returning military personnel who present with compatible symptoms despite being vaccinated.

Development of a Poly-ε-Lysine Contact Lens as a Drug Delivery Device for the Treatment of Fungal Keratitis.

Purpose: The purpose of this study was to develop a more efficient drug delivery device to overcome the limitations of current drop therapy for the treatment of fungal keratitis. Methods: Amphotericin B (AmpB), 0 to 30 µg/mL, was associated with a poly-ε-lysine (pεK) hydrogel. Fungicidal effect against Candida albicans was assessed at 18 and 42 hours by optical density (OD600) and growth on agar. Tear film dilution effect was mimicked by storage of AmpB pεK gels in 3.4 mL sterile PBS for 24 hours prior to fungal incubation. Drug elution over 96 hours was evaluated by HPLC, and drug stability was tested while associated with the gel by OD600 up to 48 hours. Lack of cytotoxicity toward the HCE-T corneal epithelial cell line was assessed over 7 days. Results: AmpB pεK gels show fungicidal activity in normal conditions (0.057 OD600, SD 0.003, P < 0.005) and in the presence of horse serum (0.048 OD600, SD 0.028 P < 0.005) at 18 hours. The drug release profile was above therapeutic levels (0.188 µg/mL) for up to 72 hours. Tear dilution had no significant effect at higher concentrations of AmpB (3 to 10 µg/mL). AmpB pεK gels were not cytotoxic to the HCE-T cell line. Conclusions: We demonstrated that AmpB pεK gels confer sustained therapeutic antifungal activity for at least 48 hours without corneal epithelial cell line cytotoxicity, suggesting their potential for in vivo use as an antifungal bandage contact lens. This could avoid the need for intensive topical medication in the treatment of fungal keratitis.