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.

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.

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.

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.

Purpose To quantify the effect of cataract surgery on cornea shape. Methods Patients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included. Repeat biometric measurements were taken before surgery and at 6 weeks on both operated and unoperated fellow eyes. Data were transformed into Long’s formalism for analysis. Device-specific measurement error was determined. The main outcome measure was the change in keratometry taking into account the change in keratometry of the unoperated fellow eye. Secondary outcome measures included the variability introduced due to location of the incision. Results 132 patients were included. The mean change in keratometry of the operated eye was −0.23@111/+0.21@21 (95% CI −1.43@122/+0.04@32 to +1.04@135/+0.30@45). The flattening effect of the surgical incision was greater and more variable than the steepening effect (p<0.01), particularly if the incision was in the flat meridian. Coupling, defined as ratio of the keratometric change in the preoperative meridians of K2 and K1, varied from 0.91 (SD 2.31) for eyes with an incision in the steep meridian, 0.75 (SD 1.81) for an incision in the flat meridian to 0.28 (SD 2.06) when the incision was made in a neutral meridian. Conclusion Cataract surgery has a slightly greater flattening than steepening effect on corneal shape. Although the effects are very small and variable with incomplete coupling, it is preferable to place the incision in the steep meridian. Greater emphasis, however, should be placed on eye-specific factors, such as biometry, or patient-related factors to optimise refractive outcomes.

Bacterial keratitis is an important cause of preventable vision loss worldwide. In this study, we aimed to synthesise the evidence for regional and temporal differences in antimicrobial resistance that could influence the choice of empirical therapy. For this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science, clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform from their date of database inception to Oct 3, 2025, for studies that reported the in-vitro susceptibility of bacterial isolates from eyes with keratitis, with no restrictions on age, publication date, or language. We excluded animal studies, single case reports, reviews, conference proceedings, editorials, grey literature, unpublished studies, and studies with an incomplete description of the anatomical source of the samples or samples collected from the conjunctiva. We excluded studies that recruited exclusively from settings such as intensive care or only included individuals with specific syndromes or other disease groups. Except for meticillin-resistant Staphylococcus aureus, studies that only reported resistant or multiresistant bacterial isolates were excluded. We contacted study authors for further information, as required. We pooled data using a random-effects meta-analysis of proportions and examined susceptibility by Global Burden of Disease super region and changes over time. The main outcome was the proportion of susceptible isolates for each drug-pathogen combination. This study was registered with PROSPERO (CRD42023331126). We extracted data from 340 reports of samples collected between 1975 and 2024 from 47 countries, with eligible data from 129 388 cases of culture-positive keratitis. Most reports were from high-income countries (158 [47%] of 340), south Asia (85 [25%]), or east Asia and the Pacific (40 [12%]), with other regions being deficient in data in comparison. The susceptibility of coagulase-positive Staphylococcus spp to ciprofloxacin in reports from south Asia was 70·8% (95% CI 60·1-79·6), which was lower than that in reports from high-income countries (86·9%, 81·5-90·9). The susceptibility of Pseudomonas spp to ciprofloxacin in reports from south Asia was also lower (80·2%, 95% CI 72·9-85·9), than that in reports from east Asia and the Pacific (96·8%, 94·5-98·1), high-income countries (98·3%, 97·4-98·9), and north Africa and the Middle East (93·8%, 87·4-97·1). We found no conclusive evidence for reduced susceptibility over time for any drug-pathogen combination. Regional differences exist in antimicrobial resistance for some clinically relevant drug-pathogen combinations. A standardised reporting template would reduce heterogeneity and facilitate future research. The National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust.