Objectives: To assess diurnal changes, topographical differences, and day-to-day repeatability of ocular surface epithelial immune cell (EIC) density and morphology in dry eye disease (DED). Methods: Sixteen participants with moderate-to-severe DED (mean (SE) age 49.4 (4.2) years) underwent in vivo confocal microscopy at three timepoints (day-1 morning and evening and day-2 morning) at six locations: central cornea, inferior whorl, inferior cornea, and temporal cornea, limbus and conjunctiva. Diurnal and topographical variation in EIC density and morphology were analyzed using linear mixed-effects models with adjusted pairwise comparisons. Day-to-day repeatability was assessed using the coefficient of repeatability (CoR) for density and Cohen's kappa for morphology. Results: EIC density and morphology varied by location (p < 0.001) but not by timepoint at any location (p = 0.59-0.90). Density was highest at the inferior cornea (model-estimated mean: 101.2 (SE: 21.7) cells/mm2) and temporal limbus (104.3 (22.7) cells/mm2), and lowest at the central cornea (26.8 [5.1] cells/mm2 and inferior whorl (38.3 [8.2] cells/mm2; all pairwise, p < 0.001). EICs with large bodies were more frequent in conjunctiva (100%), inferior cornea (94%), and temporal cornea (87%), than in central cornea (34%) and whorl (19%) (all p ≤ 0.007). EICs with dendrites, and with long dendrites were similarly distributed (p < 0.001). Bland-Altman analysis showed low mean bias and EIC density was more repeatable at the central (CoR ± 23.8 cells/mm2) and temporal cornea (±27.5 cells/mm2) than the inferior cornea (±47.9 cells/mm2) or temporal conjunctiva (±42.3 cells/mm2). Morphology agreement was substantial to near-perfect (κ = 0.71-0.97). Conclusions: In DED, EIC density and morphology are diurnally stable and maintain topographic distribution patterns similar to healthy eyes. Day-to-day repeatability show location dependent patterns. The study provides feasibility data for using IVCM for EIC metrics in disease monitoring.

PurposeDespite the revolution of artificial intelligence (AI), its integration remains limited in healthcare. A comprehensive understanding of the barriers to implementation is crucial to enhance the utilisation of AI. This study applies a conceptual framework-based analysis, to explore stakeholder perspectives of implementation barriers of AI in digital diagnosis in eye care.MethodsPurposive sampling was used to identify key individuals across stakeholder groups, including technology developers, clinicians, patients and healthcare leaders. Semi-structured interviews were conducted with 37 stakeholders. Using the updated Consolidated Framework for Implementation Research (CFIR), responses to the question: 'What is the biggest barrier to digital diagnosis or AI for macular disease in Australia?' were analysed. Barriers identified by stakeholders were mapped to thematic constructs of the updated CFIR, and the prominence of each implementation barrier was measured. Data saturation was not assessed.ResultsFor clinicians and developers, the 'innovation' domain was most frequently cited. Clinicians were most concerned with the costs involved, whereas for developers, a lack of evidence surrounding real-world application was the main challenge. For leaders and patients, 'individuals' domain was the most frequently cited. Leaders were focused on the innovation deliverers: expressing the potential risk of over-reliance on the innovation and the subsequent consequence of clinician deskilling. Patients were more concerned about innovation recipients: emphasising the perceived lack of human empathy with the implementation of AI.ConclusionsDifferences were revealed in the identified barriers to the implementation of AI across stakeholder groups. A co-design approach to address the misalignment in key barriers may be essential to the successful implementation of AI in digital health innovations.

The current advancements in quantum dot-based ocular surface applications identify critical gaps in existing research. A systematic search was conducted following PRISMA guidelines. Articles were retrieved from PubMed and Scopus using keywords including "quantum dots," "semiconductor nanocrystals," "ocular surface," "tear film," "cornea," "conjunctiva," "lacrimal glands," and "meibomian glands" with Boolean conjunctions. A total of 232 studies were initially selected based on titles and abstracts. After removing duplicates and screening, 21 studies were selected for review. A variety of QDs, including carbon, graphene, silicon, cadmium and gold-based, have been explored for bioimaging and therapeutic applications targeting the ocular surface. Carbon and silicon-based QDs are the most biocompatible. Surface functionalization of these QDs facilitates targeted imaging of tear film layers, conjunctiva, and cornea with stable fluorescence and minimal toxicity. QDs can also be antimicrobial, anti-inflammatory, and scavenge reactive oxygen species which might be used for the treatment of dry eye disease. Although cadmium-based QDs exhibit superior fluorescence, their cytotoxicity limits their clinical application. The optical properties of QDs are influenced by physicochemical properties such as particle size, surface charge, and surface functionalization. QDs represent a promising class of nanoscale materials for diagnostic and therapeutic applications on the ocular surface. While biocompatible variants of QDs, such as carbon and silicon QDs, show potential for clinical use, there is limited information on the standardized synthesis protocols, long-term cytotoxicity, systemic biodistribution, and clearance from ocular tissues. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

PURPOSE:To investigate the role of the exoU gene in biofilm formation by comparing wild-type and an exoU knockout mutant of Pseudomonas aeruginosa isolated from microbial keratitis (MK). METHODS:Biofilm formation by nine exoU-positive P. aeruginosa strains from MK was assessed using the crystal violet assay. The strain exhibiting the highest biofilm production was selected for exoU deletion via homologous recombination using the recombineering plasmid pCasPA. Successful deletion was confirmed using exoU-up-F and exoU-down-R primers and exoU gene specific primers. Cytotoxicity of the wild-type and mutant strains was compared in human corneal epithelial cells using MTT assay. Changes in biofilm between wild-type and mutant strains were assessed using crystal violet assays and confocal laser scanning microscopy (CLSM). Biofilm-associated antibiotic tolerance was assessed by treating pre-formed biofilms of the wild-type and exoU mutant strains with ciprofloxacin and levofloxacin, followed by quantification of surviving bacteria. RESULTS:PA169 P. aeruginosa produced the highest biofilm amount (OD570/OD660 nm = 2.2 ± 0.15) among the tested strains, and the exoU gene was subsequently deleted from this strain. Biofilm formation was significantly reduced in the mutant (OD570/OD660 nm = 1.4 ± 0.08) compared to its wild-type counterpart (OD570/OD660 nm = 2.2 ± 0.15, p < 0.01). CLSM confirmed a decrease in biofilm thickness in the mutant strain relative to the parent strain (8.33 ± 0.58 μm vs 11.67 ± 0.58 μm, respectively, p < 0.01). Biofilm-associated antibiotic tolerance was also reduced in the exoU mutant, which showed significantly lower survival than the wild-type strain after exposure to ciprofloxacin at 1× MIC (66.87 ± 4.46% vs 88.38 ± 10.09%) and 10× MIC (49.47 ± 6.36% vs 73.74 ± 7.63%), and levofloxacin at 4× MIC (55.29 ± 14.14% vs 79.80 ± 12.25%) and 20× MIC (12.63 ± 1.59% vs 38.13 ± 3.06%) (all p ≤ 0.03). Additionally, the mutant produced lower cytotoxicity than the wild-type (OD570 8.2 ± 0.23 vs 2.1 ± 0.25, p < 0.01). CONCLUSION:This pilot study suggests that the exoU gene may be associated with biofilm formation and biofilm-associated antibiotic tolerance in the PA169 strain. However, these findings are based on a single clinical strain, and no complementation assay was performed to rule out polar effects of the gene knockout. Further experimental work, including knockout of additional strains, complementation, and strand-specific transcriptomic analysis, is needed to determine whether the observed phenotypic changes are directly caused by deletion of the exoU gene.

Microbial keratitis (MK) is a rapid and devastating infection that can result reduced vision, with lack of treatment potentially resulting in stromal necrosis and even permanent vision loss. Pseudomonas aeruginosa is a common cause of MK and its rise in antibiotic resistance has made it increasingly difficult to treat. This review aims to provide a better understanding of the resistance mechanisms of P. aeruginosa and highlights major adaptations to combat fluoroquinolones, aminoglycosides, β-lactams and polymyxin antibiotics commonly used in MK, and addresses the global resistance profiles of P. aeruginosa keratitis. A narrative review was conducted using PubMed, Scopus, Web of Science, MEDLINE, and Google Scholar. Search terms included “Pseudomonas aeruginosa”, “microbial keratitis”, “antibiotic resistance”, antibiotic class-specific resistance terms, “surveillance studies”, and “regional resistance patterns” to consolidate current information of the various intrinsic, acquired and adaptive resistance mechanisms of P. aeruginosa conferred across fluoroquinolones, aminoglycosides, β-lactams and polymyxin along with resistance profile of keratitis isolates across continents. P. aeruginosa displays complex resistance mechanisms, including intrinsic efflux systems, reduced porin permeability, enzymatic drug inactivation, horizontal gene transfer, and target-site mutations, contributing to MDR in MK. Resistance patterns vary markedly by region, with higher resistance to fluoroquinolones, cephalosporins, and aminoglycosides reported in Asia, while Europe and North America showed lower rates. Australian isolates demonstrate heterogeneous resistance, retaining susceptibility to aminoglycosides. Future studies comparing resistance mechanisms and data of P. aeruginosa across regions will be essential to identify geographical variations, inform region-specific surveillance, guide targeted therapies to improve interventions of MK.

Microbial keratitis (MK) caused by Pseudomonas aeruginosa is a rapidly progressive and vision-threatening corneal infection worldwide. Even short delays in diagnosis or inappropriate therapy can lead to irreversible corneal scarring and blindness. This opportunistic pathogen colonizes, invades, and damages ocular tissue by taking advantage of disruptions in the corneal epithelial barrier and using a variety of virulence factors. The aim of this study was to summarize the current understanding of P. aeruginosa’s cell-associated, and secretion system-independent virulence factors involved in MK and investigate their potential as therapeutic targets. A literature search was performed using PubMed, Scopus, Web of Science, MEDLINE, and Google Scholar to review experimental and clinical studies on P. aeruginosa keratitis, with a focus on virulence factors, host-pathogen interactions, and emerging anti-virulence strategies. Search terms included combinations of P. aeruginosa, microbial keratitis, bacterial keratitis, corneal infection, corneal ulcer, virulence factors, surface- and cell-associated virulence factors, secretion-independent and contact-dependent virulence factors, pathogenicity, and anti-virulence therapies. Flagella, type IV pili, lipopolysaccharides, outer-membrane proteins, adhesins, biofilm matrix polysaccharides (Psl, Pel, alginate), siderophores, quorum-sensing networks, and secreted metabolites such as pyocyanin may be the key virulence factors in MK. These factors can influence host-pathogen interactions, corneal immunological homeostasis, and encourage drug tolerance and bacterial persistence. Moreover, targeting cell-associated and secretion system-independent virulence mechanisms represents a promising complementary approach along with conventional antimicrobial therapy. A deeper understanding of the virulence factors may enable the design of targeted therapies. Such approaches could mitigate corneal damage and vision loss while reducing selective pressure for antibiotic resistance.

Data on myopia prevalence in Australia and associations with common systemic conditions and quality of life are limited. This study aimed to profile Australian adults self-reporting to have myopia, including co-morbidities and quality of life. This research included participants from the ongoing longitudinal 45 and Up Study. Sex and education data were collected at the baseline survey and additional data from the follow-up Health Compass survey. Responses on self-reported myopia, health and quality of life were analysed with logistic regression to assess the association between myopia and health conditions. Of the 21,384 participant responses, 54.3

Purpose Myopia is a global concern, with contact lenses and atropine eye drops offering partial effectiveness. This study aimed to develop a stable nano-micelle formulation of atropine base for contact lens loading and evaluate its release profile. Methods Atropine base nano-micelles were formulated using poloxamer 407 in phosphate-buffered saline (PBS) at pH 6.5 and 7.4. Stability was monitored over a year at room temperature (21°C) using High-Performance Liquid Chromatography (HPLC), while particle sizes were measured with a zetasizer. Acuvue 2 (etafilcon A) and MiSight (omafilcon A) contact lenses were soaked in formulations for 24 hours, and atropine base absorption and release were quantified by HPLC. Cytotoxicity was assessed on human corneal epithelial cells (HCECs) following ISO 10993-5 standards. Results Micelle particle sizes ranged 190–459 nm. After one year, 88% of atropine base remained stable at pH 6.5, while 48% remained at pH 7.4. MiSight lenses loaded with 0.1 g poloxamer 407 in PBS (pH 6.5) absorbed 4 ± 0.1 µg atropine base, with 81% released in 4 hours. Most formulations were non-toxic, with ≤ 30% HCECs death. Conclusions The atropine base nano-micelle formulation at pH 6.5 demonstrated superior long-term stability and enabled drug loading into and subsequent release from contact lenses. Although most nano-micelle formulations exhibited acceptable cytocompatibility, further optimisation and comprehensive evaluation are required before their suitability for in vivo studies can be established.

Infection control (IC) is central to safe optometric care, yet little is known about optometrists’ knowledge, attitudes and practice behaviours (KAP) in this domain. This study aimed to assess the IC-related KAP of Australian optometrists and to evaluate whether engagement with newly released IC guidelines could improve these measures. This study comprised two components: a cross-sectional survey of Australian optometrists’ IC-related KAP (part A) and a pre-post intervention study assessing the impact of IC guidelines (part B). The survey, distributed in early 2021, included demographic items, KAP measures and explored perceived barriers to best practice and preferred educational resources. Knowledge was assessed using multiple-choice and true/false questions, while attitudes and behaviours were analysed using Rasch-scaled measures. Participants consenting to follow-up were randomised into control or intervention groups. The intervention group received updated IC guidelines before repeating the survey; the control group repeated the survey prior to guideline exposure. A total of 302 valid responses were analysed in part A. Respondents demonstrated moderate knowledge (mean 58

Purpose: To analyse the resistance and genetic changes of a sensitive ocular isolate of Pseudomonas aeruginosa to repeated exposure to subinhibitory concentrations of ciprofloxacin. Methods: A ciprofloxacin-sensitive ocular isolate P. aeruginosa PA123 was serially passaged under gradually increasing sub-inhibitory concentrations of ciprofloxacin for 18 passages. The minimum inhibitory concentration (MIC) was determined daily using the broth microdilution method, and after 18 passages when resistance had plateaued, ciprofloxacin was withdrawn and passaging continued for a further 13 days. A control culture in the absence of ciprofloxacin was passaged sequentially for 31 days. Genomic DNA from selected passages was extracted and subjected to whole-genome sequencing. Sequencing reads were quality-trimmed using Trimmomatic 0.38 and then analysed with Snippy 4.6.0 to identify acquired mutations using parent PA123 (non-passaged) as a reference strain. Results: The parent strain had an initial MIC of 1 µg/mL, this increased during growth in sub-MIC ciprofloxacin two-fold at passage 4 (2 µg/mL), then progressively increased to 64 µg/mL at passage 15, at which it remained for a further three passages. Upon removal of ciprofloxacin, there was no change of the MIC (64 µg/mL) during the subsequent 13 passages. In early passages (P1-P7), PA123 acquired a Leu240 frameshift mutation in mexS, while in intermediate and later passages, Thr83Ile, Ala51Val, Asp87Tyr, duplication of alanine at position 570 (Ala570dup) mutations occurred in gyrA gene. Isolates from control passages acquired only background mutations unrelated to ciprofloxacin resistance. Conclusion: Stepwise accumulation of mutations in mexS and gyrA under sub-inhibitory ciprofloxacin pressure might lead to high-level resistance in PA123, with MICs remaining elevated even after drug removal, demonstrating stable resistance and linking sub-MIC exposure to resistance evolution.

The tear film, consisting of the aqueous and lipid layers, maintains the homeostasis of the ocular surface; therefore, when disturbed, it can cause dry eye, which affects millions of people worldwide. Understanding the dynamics of the tear film layers is essential for developing efficient drug delivery systems for dry eye disease. Quantum dots (QDs) offer the potential for real-time monitoring of tear film and evaluating its dynamics. Hydrophilic silicon QDs (Si-QDs) have already been optimised to image the aqueous layer of the tear film. This study was conducted to optimise hydrophobic Si-QDs to image the lipid layer of the tear film. Si-QDs were synthesised in solution and characterised by transmission electron microscope and spectrofluorophotometry. The fluorescence emission of Si-QDs was monitored in vitro when mixed with artificial tears. The cytotoxicity was assessed in cultured human corneal epithelial cells using an MTT assay following 24 h of exposure. Si-QDs were 2.65 ± 0.35 nm in size and were non-toxic at <16 µg/mL. Si-QDs emitted stable green fluorescence for 20 min but demonstrated aggregation at higher concentrations. These findings highlight the potential of hydrophobic Si-QDs as a biomarker for the real-time imaging of the tear film lipid layer. However, further research on surface functionalisation and preclinical evaluations are recommended for enhanced solubility and biocompatibility in the ocular surface.

PURPOSE:To explore effects of topical 1 % selenium sulfide on signs and symptoms in symptomatic contact lens-wearers, in an exploratory 4-month prospective placebo-controlled double-masked randomised trial. METHODS:Symptomatic wearers (Contact Lens Dry Eye Questionnaire-8 [CLDEQ-8] score>12) with meibomian gland dysfunction (meibomian gland score (MGS)≤12), were enrolled and received either active (AZR-MD-001-containing 1 % selenium sulfide), or vehicle ointment, to the lower eyelid margin twice-weekly. MGS, meibomian glands-yielding liquid secretion (MGYLS), lipid layer thickness, tear meniscus height, tear break-up time, tear evaporation rate, lid wiper epitheliopathy, CLDEQ-8 and comfortable wear time (CWT) were measured at baseline and to 4-months. Differences between active and placebo were compared to baseline. RESULTS:Fourteen participants (5M:9 F, 30.8 ± 13.8 years) completed the study. In the active group, change in MGS from baseline improved by 1-month (mean difference 7.9 ± 8.0, p = 0.03), to 4-months (16.0 ± 11.3, p < 0.01). MGYLS improved from baseline by 1.5-months (4.0 ± 3.3) to 4-months (4.1 ± 4.3, p < 0.01). In the vehicle, change in MGS (12.1 ± 10.7) and MGYLS (3.9 ± 3.2) were improved at 4-months only (p < 0.01). CLDEQ-8 score improved at 1-month and 4-months compared to baseline (-4.4 ± 3.2, -5.1 ± 4.7, p ≤ 0.02) in the active and at 4-months only in the vehicle group (-4.4 ± 6.4, p = 0.02). In the active group, CLDEQ-8 visual function scores improved at 1- and 4-months (p ≤ 0.02) and CWT at 4-months (median 7 vs.10 h, p = 0.025). Other signs were unchanged. CONCLUSIONS:This exploratory study indicates that twice-weekly use of AZR-MD-001 ointment can rapidly improve gland patency and secretion in symptomatic contact lens-wearers. AZR-MD-001 reduced changeable/blurry vision and prolonged CWT, suggesting relevant future endpoints.

PURPOSE:The aim of this real-world registry study was to evaluate the quality-of-life (QoL) impact of dry eye disease (DED). The specific objectives were to determine factors affecting QoL in DED, and to evaluate the psychometric properties of the Ocular Surface Disease Index (OSDI), Ocular Comfort Index (OCI), and Patient Health Questionnaire (PHQ) in a real-world DED population using modern psychometric methods. METHODS:This descriptive cross-sectional study included 368 DED patients (mean 54.7 ± 16.6 years; 80.2 % female) who completed one or more of the three questionnaires (OSDI, OCI and PHQ). Psychometric analysis of the QoL data was carried out with Andrich's Rating Scale Model of Rasch analysis. RESULTS:The original OSDI and OCI had disordered categories. The Rasch-optimised final QoL scales (OSDI - Overall, OSDI - Symptoms [SY], OSDI - Activity limitation [AL], OSDI - Environmental trigger [EN], OCI Overall, OCI - Frequency [FR], OCI - Intensity [IN], and PHQ) had satisfactory psychometric properties. Patients diagnosed with a mixed aqueous/evaporative DED subtype had worse mean OSDI-Overall and OSDI-AL scores than individuals with evaporative DED (p = 0.012 and 0.001 respectively). Patients with corneal neuropathic pain had worse QoL scores (OSDI-Overall, OSDI-AL, OSDI-SY, OSDI-EN, OCI-Overall, OCI-FR, OCI-IN, and PHQ; all p < 0.05) than those without. Patients who reported undergoing prior treatment or procedure for DED had worse QoL scores than those who did not (all p < 0.05 except for PHQ). The associations between DED signs (tear breakup time and staining) and symptoms were weak or not significant. CONCLUSIONS:In this real-world setting, diagnoses of mixed DED, corneal neuropathic pain, and history of DED treatment/procedures were associated with worse dry eye symptoms, activity limitation, and/or QoL.

OBJECTIVES:This study aimed to estimate direct and indirect economic costs associated with Acanthamoeba keratitis and explore variations in individual and healthcare characteristics. METHODS:Patients treated at Moorfields Eye Hospital, UK, between January 2011 and August 2014 were surveyed. Patients were included if they had a confirmed diagnosis and wore contact lenses. Direct costs included healthcare expenses, whereas indirect costs encompassed lost wages for patients and caregivers. The Mann-Whitney U test and generalized linear models were used to analyze cost data and their associated factors, with P <0.05 being considered statistically significant. RESULTS:A total of 73 patients were included, with a mean age of 39.3 years (19-81); 40 patients (54.8%) were female, and 41 (56.2%) had good outcomes. Median direct, indirect, and total costs were £2,966.5 (IQR £5,553.2), £1,776.0 (IQR £3,223.3), and £6,678.6 (IQR £17,268.4), respectively. Higher direct costs were independently associated with multiple medical visits ( P <0.001), steroids before antiamoeba therapy ( P =0.042), and keratoplasty ( P <0.001). CONCLUSIONS:The cost of managing Acanthamoeba keratitis is substantial. Future research should focus on optimizing treatment strategies and improving patient outcomes to help alleviate the financial burden on patients and healthcare systems.

This report provides an evidence-based review of current strategies to manage dry eye disease (DED). First-line management focuses on methods to replenish, conserve, and stimulate the tear film, with an emphasis on ocular supplements, which remain the cornerstone of DED treatment. Meibomian gland dysfunction, a primary contributor to DED, is typically treated with warm compresses and a wide variety of in-office treatments, including device-driven technologies to warm the eyelids, intense pulsed light therapy, low-level light therapy, and other new and emerging technologies. Lid hygiene treatments include lid wipes, anti-Demodex therapies, blepharoexfoliation, and topical antibiotics. DED caused by certain etiological drivers can benefit from anti-inflammatory therapies, including topical and oral corticosteroids, T-cell immunomodulatory drugs, and a wide variety of pharmacological agents, in addition to biologic tear substitutes such as autologous serum and platelet-rich plasma. Emerging therapies, such as neuromodulation via nasal neurostimulation and novel pharmacological treatments, offer potential future options. Advanced options, including amniotic membrane grafts and complex surgical methods, provide options for severe or refractory cases. Lifestyle modifications, including optimized blinking, dietary supplementation, and environmental adjustments, play a crucial role in long-term management. Patient education and adherence to treatment regimens remain essential for sustained symptom relief. The TFOS DEWS III prescribing algorithm provides an evidence-based framework to offer guidance to clinicians in selecting relevant interventions based on disease etiology that aim to provide targeted management of the relevant DED subtype(s) that an individual is experiencing.

PURPOSE:This study aimed to explore the lived experience of adults with different types of ocular surface disease (OSD) to understand their quality of life (QoL) impacts. METHODS:Lived experiences of participants diagnosed with aqueous deficient dry eye disease (DED), meibomian gland dysfunction (MGD), anterior blepharitis, neuropathic corneal pain (NCP), ocular surface involvement of autoimmune disease and contact lens discomfort (CLD) were explored using in-depth, semi-structured interviews. Participants were recruited from specialized dry eye clinics in Australia, United Kingdom, as well as online support groups. Thematic analysis of interviews was performed to identify key QoL themes. RESULTS:Sixty-two participants participated in an in-depth interview (median age: 46 years, range 22-78). There were 16 male participants (median age: 38.5 years; range: 23-74) and 46 female participants (median age: 50 years; range 22-78). The distribution of participants by condition as follows: DED - 9, MGD - 12, anterior blepharitis - 8, NCP - 8, ocular surface involvement of autoimmune disease - 14, and CLD - 11. Thirteen major QoL themes emerged. The most significant impact observed was on the emotional wellbeing with participants describing feelings of annoyance, depression, frustration, reduced self-confidence, worry, and anxiety related to their condition. Many expressed concerns about the chronic nature of OSDs, characterised by persistent symptoms and lifelong treatment. Economic impact extended beyond direct medical expenses, affecting employment, and productivity. Participants also described difficulties with daily activities, driving and mobility. Coping strategies included adjustments to their daily routine and environment. CONCLUSION:OSDs significantly impact multiple aspects of an individual's life. These findings lay the foundation for developing a comprehensive and technologically advanced patient reported outcome measure (PROM) tailored to individuals with OSDs. Addressing these QoL concerns through targeted interventions and policy updates will be crucial in enhancing patient care and optimizing disease management.

Dry anophthalmic socket syndrome (DASS) is a complex and multifaceted condition that commonly affects patients who have undergone enucleation or evisceration and wear an ocular prothesis. The diagnosis and management of DASS poses significant challenges due to the absence of a standardized diagnostic criteria and evidence-based treatment protocol. Though DASS symptoms can be disproportionate to observable clinical signs, patient-reported outcomes and scoring systems remain the cornerstone of its diagnostic framework. While a dearth of literature exists, parallels can be drawn from other ocular surface conditions, including dry eye disease and contact lens-associated dry eye, regarding inflammatory pathways and surface interactions. DASS is postulated to be related to disruptions to tear film homeostasis, lid margin disease, and chronic inflammation driven by mechanical friction between the prosthesis and socket tissues. We provide a comprehensive review of the pathophysiological processes underlying DASS, discussing current and evolving diagnostic approaches, including use of symptom questionnaires and objective biomarkers such as tear film osmolarity and matrix metalloproteinase-9. Emerging concepts, such as detailed mechanisms of chronic inflammation and the precise nature of mechanical interactions will also be evaluated, alongside future directions for research aimed at optimising guidelines to improve patients' quality of life.

BACKGROUND:The aim of this study was to determine differences in susceptibility of exoU and exoS Pseudomonas aeruginosa to multi-purpose disinfecting solutions (MPDS) and antibiotics and their association with disinfectant resistance genes. METHODS:A total of 16 exoU and 24 exoS P. aeruginosa keratitis isolates were tested for susceptibility against four multipurpose disinfecting solutions (OPTI-FREE PureMoist, Acuvue RevitaLens, Biotrue, and Renu Advanced Formula) using minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. Antibiotic susceptibility to ciprofloxacin, levofloxacin, gentamicin, and tobramycin was determined by MIC. Whole genome sequences from 27 isolates were utilized to identify disinfectant resistance genes and single nucleotide polymorphisms (SNPs) in the genes using the Comprehensive Antibiotic Resistance Database (CARD) and Geneious Prime respectively. Polymerase chain reaction (PCR) was used to detect the disinfectant resistance genes qacE, qacEΔ1, and sugE1. Correlation between disinfectant resistance genes and their SNPs with disinfectant and antibiotic MICs was determined by Spearman's Rho. RESULTS:All MPDS were bactericidal at full strength, but upon dilution OPTI-FREE Puremoist and Renu Advanced Formula were the most active against the exoU and exoS groups correspondingly. ExoU showed significantly higher resistance than exoS (p ≤ 0.04) to levofloxacin (37.5 % vs. 8.3 %), gentamicin (43.8 % vs. 0 %), and tobramycin (37.5 % vs. 0 %). The qacEΔ1 and sugE1 genes along with several SNPs in the resistance genes were more common in the exoU group. SNPs in disinfectant resistance genes correlated with MPDS MICs/MBCs, notably mexQ Arg1036His (R ≥ -0.38, p ≤ 0.04), Gly505Asp (R ≥ 0.40, p ≤ 0.04) and opmD Gly269Ser (R ≥ 0.43, p ≤ 0.03). QacEΔ1 and sugE1 were linked to increased MIC (R ≥ 0.54, p < 0.01) and MBC (R ≥ 0.50, p < 0.01) for Renu Advanced Formula. Also, multiple SNPs and qacEΔ1 and sugE1 showed moderate to large positive associations with antibiotic resistance. CONCLUSIONS:ExoU strains had distinct MPDS susceptibility patterns, with higher disinfectant resistance genes prevalence and mutations, contributing to MPDS and antibiotics resistance.

A standard approach to the diagnosis of dry eye disease across eye care practitioners is critical to reassuring the patient, providing consistency between practitioners and informing governments as to the true prevalence and resulting healthcare needs. The Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) III has reviewed the evidence-base since their previous reports published in 2017 and revised the definition to "Dry eye is a multifactorial, symptomatic disease characterized by a loss of homeostasis of the tear film and/or ocular surface, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities are etiological factors." Key features from the definition include that dry eye disease is multifactorial, is a disease and not a syndrome and is always symptomatic. Differential diagnosis and ocular examination guidance is given along with the risk factors that should be discussed with the patient. The recommended screening questionnaire is the OSDI-6 with a cut-off score ≥4. A positive result together with a non-invasive breakup time <10s or alternatively tear film hyperosmolarity (≥308mOsm/L in either eye or an interocular difference >8mOsm/L) or alternatively >5 corneal fluorescein and/or >9 conjunctival lissamine green punctate spots and/or lid margin lissamine green staining of ≥2mm length & ≥25 % width, gives a diagnosis of dry eye. Subclassification was separated into tear film deficiencies (lipid, aqueous and mucin/glycocalyx), eyelid anomalies (blink/lid closure and lid margin) and ocular surface abnormalities (anatomical misalignment, neural dysfunction, ocular surface cell damage/disruption and primary inflammation/oxidative stress) components, with appropriate clinical tests and cut-offs provided to identify these etiological drivers in an individual, to inform appropriate management and therapy.