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To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180.Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED.Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.

Isolation of antimicrobial-resistant microbes from ocular infections may be becoming more frequent. Infections caused by these microbes can be difficult to treat and lead to poor outcomes. However, new therapies are being developed which may help improve clinical outcomes. This review examines recent reports on the isolation of antibiotic-resistant microbes from ocular infections. In addition, an overview of the development of some new antibiotic therapies is given. The recent literature regarding antibiotic use and resistance, isolation of antibiotic-resistant microbes from ocular infections and the development of potential new antibiotics that can be used to treat these infections was reviewed. Ocular microbial infections are a global public health issue as they can result in vision loss which compromises quality of life. Approximately 70 per cent of ocular infections are caused by bacteria including Chlamydia trachomatis, Staphylococcus aureus, and Pseudomonas aeruginosa and fungi such as Candida albicans, Aspergillus spp. and Fusarium spp. Resistance to first-line antibiotics such as fluoroquinolones and azoles has increased, with resistance of S. aureus isolates from the USA to fluoroquinolones reaching 32 per cent of isolates and 35 per cent being methicillin-resistant (MRSA). Lower levels of MRSA (seven per cent) were isolated by an Australian study. Antimicrobial peptides, which are broad-spectrum alternatives to antibiotics, have been tested as possible new drugs. Several have shown promise in animal models of keratitis, especially treating P. aeruginosa, S. aureus or C. albicans infections. Reports of increasing resistance of ocular isolates to mainstay antibiotics are a concern, and there is evidence that for ocular surface disease this resistance translates into worse clinical outcomes. New antibiotics are being developed, but not by large pharmaceutical companies and mostly in university research laboratories and smaller biotech companies. Antimicrobial peptides show promise in treating keratitis.

Contact lens wear is generally safe and provides excellent vision. However, contact lens wear is often associated with the risk of developing ocular surface infection and inflammation, and in severe cases, the infection can result in loss of vision. Antimicrobial peptide-coated contact lenses have been made to help reduce the incidence of infection and inflammation. This paper reviews the research progress from conception, through the laboratory and preclinical tests to the latest information on clinical testing of an antimicrobial contact lens. We provide insights into the pathways followed and pitfalls that have been encountered. The journey has not always been linear or smooth, but has resulted in some of the first published clinical testing of antimicrobial peptide-coated contact lenses in humans. We hope this may help lead to the development and commercialisation of antimicrobial contact lenses in the future.

Corneal confocal microscopy (CCM) has been identified as a non-invasive technique to assess corneal nerve fiber morphology. It is not known how corneal nerve changes relate to measures of peripheral nerve function in diabetic peripheral neuropathy (DPN). The present study investigates the relationship between nerve structure and function in DPN.Fifty participants with type 1 diabetes (T1DM) and 29 healthy controls underwent CCM to assess corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), nerve fractal dimension (CNFrD) and inferior whorl length (IWL). The severity of DPN was assessed as Total Neuropathy Score (TNS). Motor nerve axonal excitability tests were conducted to assess axonal function.Significant correlations were noted between CNFD (rho = -0.783; P 0.01) or superexcitability (rho = 0.435; P 0.01) and TNS. CNFrD was significantly correlated with peak response to stimulus (r = 0.414; P 0.01) and superexcitability (r = -0.467; P 0.01) measurements.Corneal nerve loss demonstrates a significant association with axonal ion channel dysfunction in T1DM.Detection of altered corneal nerve morphology may lead to the earlier diagnosis of DPN.

Protection against pathogens using personal protective equipment is essential yet challenging in healthcare settings. Concerns over emerging biothreats and outbreaks of infectious diseases underscore the need for antimicrobial and biocompatible protective clothing to protect patients and staff. Herein, we report the antimicrobial efficacy and cytotoxicity of cotton/silk fabrics containing embedded reduced graphene oxide (RGO) and Ag/Cu nanoparticles (NPs), prepared using a 3-glycidyloxypropyl trimethoxy silane coupling agent followed by chemical reduction and vacuum heat treatment. Embedding NPs on top of the RGO layer substantially increased the antimicrobial activity. All RGO-Ag NPs or RGO-Cu NPs embedded in cotton or silk fabrics reduced the viability of approximately 99% of the Gram-negative bacteria

Purpose: To evaluate the effect of age, gender and body mass index (BMI) on the levels of tear film neuromediators and corneal nerve parameters in healthy individuals.Methods: Twenty-six he...

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia).However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation.In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.

Significance Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. Purpose The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. Methods Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. Results The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. Conclusions The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain.

The purpose of this study was to investigate the effect of Mel4 antimicrobial peptide-coated contact lenses (MACL) on the microbiota of the conjunctiva and lenses during three months of extended wear.One hundred and seventy-six participants were recruited into a randomised, contralateral, double masked, biweekly extended wear MACL and uncoated control lens trial. At the one month and 3-month visit, the conjunctival microbiota was sampled using sterile cotton swabs and contact lenses were collected aseptically. Standard microbiological procedures were employed for culture of the swabs and contact lenses and identification of the isolated microorganisms.Gram-positive bacteria (predominantly coagulase-negative staphylococci) were the most frequently isolated microbes from both contact lenses and conjunctiva. There was no difference in the frequency of isolation of most bacteria or fungi from the conjunctival swabs of eyes wearing either MACL or control lenses. The only exception was a higher frequency of eyes harbouring Staphylococcus arlettae when wearing control lenses (5%) versus MACL (1%) (p = 0.002). There was no significant difference in the frequency of microbes isolated from MACL or control contact lenses. There were also no differences between lens types in the frequency of isolation of1 microbial type per sampling occasion for either conjunctiva swabs or contact lenses.MACL wear did not change the conjunctival microbiota during extended wear, and the types of microbes isolated from MACL were similar to those isolated from control lenses.

Frequent replacement contact lenses made from the etafilcon A hydrogel lens material were introduced onto the market over 30 years ago, and etafilcon A remains the most widely used hydrogel lens material today. Although the prescribing of silicone hydrogel lenses is increasing, millions of lens wearers globally have been wearing hydrogel lenses for many years and exhibit a physiologically-stable ‘quiet eye’, with a low profile of adverse events. Hydrogel lenses are demonstrated to maintain a low inflammatory response and infection risk profile during daily wear, which in the case of etafilcon A, may be related to its low modulus, and the naturally-protective, anti-microbial, non-denatured lysozyme absorbed into the lens from the tear fluid. Although improved corneal physiology from decreased hypoxia with silicone hydrogel lenses is well accepted, equivalent levels of corneal oxygenation are maintained during daily wear of low to medium powered hydrogel lenses, which do not impede the daily corneal de-swelling process, and do not induce clinically significant changes in ocular health. Therefore, hydrogel lenses remain an important alternative for daily wear in modern contact lens practice.

A novel coronavirus (CoV), the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), results in the coronavirus disease 2019 (COVID-19). As information concerning the COVID-19 disease continues to evolve, patients look to their eye care practitioners for accurate eye health guidance. There is currently no evidence to suggest an increased risk of contracting COVID-19 through contact lens (CL) wear compared to spectacle lens wear and no scientific evidence that wearing standard prescription spectacles provides protection against COVID-19 or other viral transmissions. During the pandemic there will potentially be significant changes in access to local eyecare. Thus, it is imperative CL wearers are reminded of the steps they should follow to minimise their risk of complications, to reduce their need to leave isolation and seek care. Management of adverse events should be retained within optometric systems if possible, to minimise the impact on the wider healthcare service, which will be stretched. Optimal CL care behaviours should be the same as those under normal circumstances, which include appropriate hand washing (thoroughly with soap and water) and drying (with paper towels) before both CL application and removal. Daily CL cleaning and correct case care for reusable CL should be followed according to appropriate guidelines, and CL exposure to water must be avoided. Where the availability of local clinical care is restricted, practitioners could consider advising patients to reduce or eliminate sleeping in their CL (where patients have the appropriate knowledge about correct daily care and access to suitable lens-care products) or consider the option of moving patients to daily disposable lenses (where patients have appropriate lens supplies available). Patients should also avoid touching their face, including their eyes, nose and mouth, with unwashed hands and avoid CL wear altogether if unwell (particularly with any cold or flu-like symptoms).

Purpose This study examined the rate and level of microbial contamination of silver and non-silver (control) barrel contact lens storage cases in vivo. Methods A prospective, single-centre, randomized, double blinded, crossover study was conducted to evaluate the efficacy of silver and control barrel cases used with an Oxipol™-based disinfecting solution over a two-month period. Lens cases were collected, and the frequency, type and level of microbial contamination evaluated using viable culture and standard identification methods. Questionnaires were used to assess the contact lens-related hygiene compliance of the participants. Results Forty eight daily contact lens wearers completed the study. Overall, 27 % of silver and 35 % control lens cases (P > 0.05) were contaminated, predominantly with Gram-positive bacteria. Only, 12 % of participants had good compliance, with 46 % having average compliance and 43 % poor compliance. Compliance score was not associated with level of microbial contamination. However, the use of hydrogel lenses in combination with silver cases compared to non-silver barrel cases resulted significantly greater numbers of bacteria colonising cases. Conclusion The present investigation demonstrated that the use of silver barrel cases does not reduce the overall rate and level of bacterial contamination, but that using hydrogel lenses in combination with silver cases resulted in higher numbers of bacteria isolated from cases.

Objective To investigate differences in SNPs in TLR genes between people who had keratitis and controls in an Indian population. Methods 145 cases of keratitis and 189 matched controls were recruited. DNA was extracted from peripheral blood. Single nucleotide polymorphisms (SNP) in TLR2 (n = 6), TLR4 (n = 15), TLR5 (n = 13) and TLR9 (n = 10) were analysed. The risk of developing keratitis was assessed based on allele, genotype and haplotype associations. Results For all cases of keratitis, the TLR4 SNP rs4986791 TC genotype frequency was significantly higher in cases (p = 0.006, OR = 1.96, 95 % CI 1.19–3.2). Including cases of only microbial keratitis (MK) revealed that genotypes in TLR2 SNP rs5743706 TA (p = 0.0001; OR = 8.61; 95 % CI 2.59–28.56)), TLR4 SNP s4986791 TC (p = 0.002; OR = 2.65; 95 % CI 1.39–5.07) were significantly more common for MK, whereas the TLR5 SNP rs2241096 A allele (p = 0.00316, OR = 0.42, 95 % CI 0.2−0.9286) and GA genotype (p = 0.016; OR = 0.45; 95 % CI 0.23−0.86) was significantly less common in MK cases. The TLR2 SNP rs5743706 genotype TA was significantly less common in the sterile keratitis (SK) group (p = 0.004, OR = 0.43, 95 %CI 0.24−0.77). Haplotype analysis of MK compared to controls showed that TLR2 AT was more common in controls (p = 0.003); TLR4 ACAC was more common in cases (p = 0.004); TLR5 TGGCA was more common in controls (p = 0.001). Conclusion The present study revealed multiple associations between variants across TLR genes, which may have implications for understanding the underlying host factors, risk of developing keratitis and molecular pathogenesis in keratitis.

Objective To assess the incidence of adverse events during the use of a povidone-iodine disinfecting solution (cleadew) and the microbial contamination in contact lens cases. Methods A prospective, single-center, open-label, controlled study evaluating the use of cleadew cleaning and disinfecting system in existing daily wear soft contact lens wearers over a 3-month period was conducted. Ocular signs and symptoms during lens wear were assessed at baseline and after 1 and 3 months of using cleadew. Contact lens cases were assessed for the frequency of microbial contamination and the types of microbes, using traditional microbial culture, followed by identification of bacteria using 16S rRNA sequencing. Results Use of cleadew was well tolerated. There was reduction in corneal staining (0.5±0.5 at 3 months of use) compared with the participant's habitual multipurpose disinfecting system (1.1±1.0); all other clinical signs were not significantly different. There were no cases of solution-induced corneal staining. There was a low adverse event rate of 0.8% per 100 participant-months. Contact lens case contamination was low, with 30% of cases having no culturable microbes. Comparison with previously published data showed that use of cleadew resulted in low frequencies of Gram-positive (49%) and fungal (8%) contamination and a low, but higher than some other disinfecting solutions, level of Gram-negative bacteria. Conclusions Cleadew cleaning and disinfecting system was associated with low levels of adverse events during use. Contact lens cases were significantly less frequently contaminated than for some other types of disinfecting solutions.

To determine the utility of corneal confocal microscopy and tear neuromediator analysis in the diagnosis of diabetic peripheral neuropathy (DPN) as a result of type 1 and type 2 diabetes.Seventy individuals with either type 1 diabetes or type 2 diabetes (T1D/T2D) underwent corneal confocal microscopy to assess the corneal nerve morphology. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Motor excitability studies were conducted on the median nerve to assess axonal ion channel function. Based on total neuropathy score (TNS), participants were stratified into DPN (DPN+ve; TNS ≥ 2; T1D, n = 19; T2D, n = 16) and without DPN (DPN-ve; TNS ≤ 1; T1D, n = 19; T2D, n = 16). Areas under the receiver operating characteristic curves (AUCs) were calculated to obtain specificity and sensitivity of the measures to diagnose DPN.In T1D, the concentration of substance P and confocal microscopy measures were significantly reduced (Corneal confocal microscopy parameters provide a better diagnostic ability to detect DPN in T1D and T2D than nerve excitability measures or concentrations of tear neuromediators. The concentration of substance P could also be useful in diagnosing DPN but for T1D only.

OBJECTIVES To evaluate the effect of microblepharon exfoliation on the number of eyelid bacteria and their lipase activity and the relationship of these to contact lens discomfort. METHODS Thirty experienced contact lens wearers had their eyelid margin physiology, tear properties, and comfort scores assessed. The number, type, and frequency of lower eyelid margin bacteria, and their lipase activity, were measured. Eyelids were treated with a foam cleanser or microblepharon exfoliation. Clinical and microbiological tests were repeated at each visit. Changes and correlations were examined. RESULTS Symptomatic lens wearers had a higher ratio for the number and frequency of gram-positive rods and cocci. Microblepharon exfoliation reduced the number and ratio of gram-positive rods to cocci from baseline for symptomatic wearers that lasted 7 to 10 days after treatment (P

Purpose To report the density and morphology of cells that are analogous to corneal Langerhans cells and their associations in keratoconus. Materials and methods This prospective cross-sectional study included a convenience sample of keratoconus subjects aged between 18-65 years. Corneal topography, assessment of ocular symptoms, tear variables, corneal sensitivity, in-vivo confocal microscopy were performed. The number of Langerhans cells were manually counted and averaged across three central corneal images. Cell morphology was graded on a 0-3 scale, where grade 3 indicates cells with long visible dendrites. Associations of Langerhans cells with other variables were evaluated using Spearman’s correlation. Results Twenty-one keratoconus subjects with a mean age of 43 ± 11 years were included. Eighty-one percent of them were males, 48% had mild keratoconus and 52% were contact lens wearers. Langerhans cells were present in the central cornea in 91% of subjects. Median cell density was 15 cells/mm2(IQR: 3-21). Cell morphology of grades 2 or 3 (with short or long dendrites) was seen in 71% of subjects. There was a significant association between Langerhans cell frequency and density with male gender (rho and p-values: -0.669, 0.001 and -0.441,0.045) and between Langerhans cell density and nerve fibre tortuosity (0.479,0.028). No significant association observed with age, contact lens wear or ocular symptoms. Conclusion Langerhans cells were present in a significant number of subjects suggesting the possibility of inflammation in keratoconus. Based on the association of Langerhans cells with nerve parameters, we propose inflammation as the underlying cause for corneal nerve changes in keratoconus.

Purpose To investigate characteristics of the eyelid margins, meibomian glands and the tear film of contact lens wearers, and to determine whether these characteristics were related to symptoms of contact lens discomfort. Methods A cross sectional study was performed on thirty existing daily wear soft contact lens wearers (6 male; 24 female) with median age of 23 years (range 18–41). Eyelid signs and tear film characteristics were evaluated during a single visit and subjects completed the contact lens and dry eye questionnaire (CLDEQ-8) to evaluate ocular discomfort. Results Based on the CLDEQ-8 responses, subjects were classified as symptomatic (n = 17) or asymptomatic (n = 13). Grades of foam at meibomian gland orifices (3 ± 1), expressibility (2 ± 1) and quality of secretions (2 ± 1), tear evaporation rate with (112 ± 54 g/m2/h) or without (88 ± 45 g/m2/h) contact lens wear, fluorescein tear breakup time (8 ± 2 seconds) and tear lipid layer thickness (45 ± 17 nm) were significantly associated with symptoms of discomfort in symptomatic lens wearers only (r2 > 0.45; p value Conclusions Morphological irregularities of the meibomian glands and alterations to tear film secretions that affect tear evaporative dynamics were associated with symptoms of discomfort amongst the symptomatic lens wearers.

Inflammasomes, key molecular regulators that play an important role in inflammation, consist of a central protein, an adaptor protein ASC (apoptosis speck-like protein) and a caspase-1 protein. Upon activation, caspase-1 induces maturation of cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). The release of these cytokines can result in inflammation. Inflammasomes are activated by a variety of factors and their activation involves complex signalling leading to resolution of infection, but can also contribute to the pathology of inflammatory, autoimmune, and infectious diseases. The role of NLRP1, NLRP3, NLRC4 and AIM2 inflammasomes in the pathogenesis of ocular diseases such as glaucoma, age related macular degeneration (AMD), diabetic retinopathy, dry eye and infections of the eye has been established over the past decade. In experimental studies and models, inhibition of inflammasomes generally helps to reduce the inflammation associated with these eye diseases, but as yet the role of these inflammasomes in many human eye diseases is unknown. Therefore, a need exists to study and understand various aspects of inflammasomes and their contribution to the pathology of human eye diseases. The goal of this review is to discuss the role of inflammasomes in the pathology of eye diseases, scope for anti-inflammasome therapy, and current research gaps in inflammasome-related eye disease.

The human eye is a complex organ with unique anatomy and physiology that restricts the delivery of drugs to target ocular tissues/sites. Recent advances in the field of pharmacy, biotechnology and material science have led to development of novel ophthalmic dosage forms which can provide sustained drug delivery, reduce dosing frequency and improve the ocular bioavailability of drugs. This review highlights the different anatomical and physiological factors which affect ocular bioavailability of drugs and explores advancements from 2016 to 2020 in various ophthalmic preparations. Different routes of drug administration such as topical, intravitreal, intraocular, juxtascleral, subconjunctival, intracameral and retrobulbar are discussed with their advances and limitations.

Purpose To determine whether Mel4-coated antimicrobial contact lenses (MACLs) can reduce the incidence of corneal infiltrative events (CIEs) during extended wear. Methods A prospective, randomized, double-masked, single-center, contralateral, extended contact lens wear clinical trial was conducted with 176 subjects. Each participant was randomly assigned to wear a MACL in one eye and an uncoated control contact lens in the contralateral eye or an extended-wear biweekly disposable modality for 3 months. The main outcome measures were the incidence of CIEs per 100 eye-months, identification of the microbial types colonizing the contact lenses or eyes at the time of the CIEs, and their susceptibility to Mel4. Results Nine participants (5.1%) experienced unilateral CIEs; six participants had contact lens acute red eye, and three participants had infiltrative keratitis. The incidence rate for CIEs (0.4 events per 100 participant months; 1.7%) in the Mel4-coated lenses (test) was 69% less than that of the control lenses (1.3 events per 100 participant months; 3.4%; P = 0.29). All Gram-negative bacteria isolated from lenses and lids of participants with CIEs (Citrobacter diversus, Acinetobacter haemolyticus, and Acinetobacter lwoffii) were susceptible to Mel4 peptide; minimum inhibitory concentrations ranged from 15.6 to 62.5 µg/mL. Reduction of adhesion of these bacteria by Mel4-coated lenses ranged from 2.1 to 2.2 log10 colony-forming units/lens. Conclusions MACLs had the capacity to reduce CIEs by at least 50% compared with uncoated control lenses during extended wear over 3 months; however, due to the relatively low rates of CIEs, the reduction was not statistically different compared with control lenses. Translational relevance This study provides evidence that antimicrobial contact lenses have the potential to reduce the incidence of corneal infiltrative events during extended wear.

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.

Prostate cancer (CaP) is the most common cancer in men and the second leading cause of cancer deaths in males in Australia. Although serum prostate-specific antigen (PSA) has been the most widely used biomarker in CaP detection for decades, PSA screening has limitations such as low specificity and potential association with over-diagnosis. Current biomarkers used in the clinic are not useful for the early detection of CaP, or monitoring its progression, and have limited value in predicting response to treatment. Urine is an ideal body fluid for the detection of protein markers of CaP and is emerging as a potential source for biomarker discovery. Gene-based biomarkers in urine such as prostate cancer antigen-3 (PCA3), and genes for transmembrane protease serine-2 (TMPRSS2), and glutathione S-transferase P (GSTP1) have been developed and evaluated in the past decades. Among these biomarkers, urinary PCA3 is the only one approved by the FDA in the USA for clinical use. The study of urine microRNAs (miRNAs) is another burgeoning area for investigating biomarkers to achieve a pre-biopsy prediction of CaP to contribute to early detection. The development of mass spectrometry (MS)-based proteomic techniques has sparked new searches for novel protein markers for many diseases including CaP. Urinary biomarkers for CaP represent a promising alternative or an addition to traditional biomarkers. Future success in biomarker discovery will rely on collaboration between clinics and laboratories. In addition, research efforts need to be moved from biomarker discovery to validation in a large cohort or separate population of patients and translation of these findings to clinical practice. In this review, we discuss urine as a potential source for CaP biomarker discovery, summarise important genetic urine biomarkers in CaP and focus on MS-based proteomic approaches as well as other recent developments in quantitative techniques for CaP urine biomarker discovery.

Objectives To describe the past 20 years' contemporary management modalities for keratoconus (KC) and their outcomes and failures and to propose recommendations in reporting their outcomes. Methods A systematic review of the literature on KC management options for the last 20 years was performed. Original articles that reported the outcome of any form of KC management other than full-thickness or lamellar corneal graft were reviewed to collect information on their outcomes and complications and the level of scientific evidence of the study. Results A total of 1,147 articles retrieved and of those, 241 satisfied the inclusion criteria, and 41.1% of them were prospective case series. The higher level of evidence studies, that is, randomized controlled trials (RCTs), were limited to only one intervention, that is, corneal collagen cross-linking (CXL). However, the quality of most RCTs was limited because of performance and detection bias. Contact lenses (CLs) remain the mainstream of KC management and were associated with reversible and non-sight-threatening complications. Surgical options such as intracorneal segment implantation and phakic intraocular lens are considered in the visual rehabilitation of CL intolerants, and CXL is the only available option to stop or delay the disease progression. Generally, these surgical procedures are associated with transient inflammatory events and permanent sequelae. Conclusions The published studies on KC management options varied significantly with respect to the study population, age of participants, severity of KC, clinical outcome measurements, and follow-up period. High-quality longer follow-up RCTs are required to evaluate the long-term effects of KC interventions.

PURPOSE To establish the effect of lipid supplements on the tear lipid layer and their influence on lens wear comfort in habitual lens wearers. METHODS Forty habitual soft contact lens wearers were recruited to a double-masked, randomized crossover trial. An emulsion drop containing phosphatidylglycerine (Systane Balance; Alcon) and a saline drop as a placebo or a liposomal spray containing phosphatidylcholine (Tears again; BioRevive) and a saline spray as a placebo were used three times a day for 2 weeks with 48 hours washout between each intervention. Ocular comfort, lipid layer grade, and stability of the tear film using a Tearscope and tear evaporation rate using a modified VapoMeter were assessed after 6 hours of lens wear with lenses in situ. RESULTS Neither of the lipid supplements improved lens wear comfort compared to baseline. The noninvasive surface drying time significantly reduced with the placebo spray at day 1 (P = .002) and day 14 (P = .01) whereas the lipid spray had no effect. With the lipid drop and placebo, noninvasive surface drying time was unchanged compared to baseline (P > .05) on day 1, but by day 14, noninvasive surface drying time was reduced with the lipid drop (P = .02) and placebo (P < .001). Symptomatic wearers showed shorter noninvasive surface drying time compared to asymptomatic wearers with the spray treatment on both days (P = .03) but not with the lipid drop (P = .64). The placebo drop significantly changed the lipid layer distribution (P = .03) with a higher percentage of thinner patterns compared to the baseline distribution at day 14. A weak but significant correlation was shown between ocular comfort and noninvasive surface drying time (r = -0.21, P = .003) and tear evaporation rate (r = 0.19, P = .008). Ocular comfort was not associated with lipid layer patterns (r = 0.13, P = .06). CONCLUSIONS Ocular comfort during contact lens wear improved with increased tear film stability and a reduced tear evaporation rate. However, the lipid supplements did not improve ocular comfort from baseline.

Purpose To evaluate corneal sensitivity and its association with other clinical parameters in keratoconus. Methods Twenty-four subjects with keratoconus aged between 18 and 65 years were recruited in this cross-sectional study. Ocular symptoms, corneal topography, tear variables such as tear osmolarity, volume and lower tear meniscus height, ocular surface staining, central sensitivity threshold (CST), and corneal subepithelial nerve mapping were obtained. Association between central CST and other clinical variables was examined using the Spearman correlation coefficient. Partial correlation was performed to control for effects of confounding factors. Results Data from the most severe eye of each subject were included in analyses. Based on the maximum simulated keratometry (Kmax) reading, subjects were graded as having mild (N = 11; K max ≤ 52 D) or severe (N = 13; K max > 52 D) keratoconus. Central corneal sensitivity was lower (ie, increased CST) in the severe keratoconus group compared with that in the mild keratoconus group (median, interquartile range: 1.09; 0.60-19.66 vs. 0.51; 0.39-1.51 g/mm, P = 0.035). In bivariate correlations, reduced corneal sensitivity in keratoconus was associated with age (ρ = 0.42, P = 0.040), disease duration (ρ = 0.49, P = 0.015) and severity (ρ = 0.44; P = 0.032), lower central nerve fiber density (ρ = -0.68, P = 0.014), contact lens wear (ρ = 0.44; P = 0.025), and contact lens tolerance (ρ = 0.46; P = 0.033). After adjusting for contact lens wear, reduced corneal sensitivity was negatively associated with ocular symptoms (ρ = -0.426, P = 0.048) and pain sensitivity (ρ = -0.423, P = 0.045) and positively associated with corneal staining (ρ = 0.52, P = 0.011). Conclusions Altered corneal sensitivity in keratoconus affected ocular symptoms and ocular surface health, which may have significant impact on the success of management options for keratoconus.

Contact lenses are associated with discomfort during wear. This may be the result of stimulation of the ocular surface and production of pro-inflammatory mediators which are then released into the tears. This study examined changes in the concentration in tears of arachidonic acid metabolites (AAM) prostaglandins, cysteinyl leukotrienes, and resolvin-DTears were collected twice a day (morning and evening) for up to 10 days on two different occasions (with and without contact lens wear) from 30 experienced contact lens wearers for analysis of AAM and a separate group (N = 33) for analysis of histamine. Ocular comfort was rated subjectively on an ordinal scale at each time of tear collection. Tears were analyzed using commercial immunoassay-based kits. Statistical analysis was performed using linear mixed model test.Ocular comfort decreased from morning to evening with and without contact lenses (p = 0.001), and the difference in comfort in the evening was greater with contact lens wear (80.9 ± 16.2 vs. 75.5 ± 16.8; p = 0.008). The total concentration of PGs (10.7 ± 10.8 ng/ml), cysteinyl leukotrienes (8.7 ± 0.38 ng/ml), resolvin-DProstaglandins, cysteinyl leukotrienes, resolvin-D1, or histamine concentrations did not alter in relation to changes in comfort of the eye during the day or during contact lens wear. These results suggest that release of these mediators is not responsible for contact lens discomfort.

Purpose The aim of this study was to examine the literature with respect to inflammation of the ocular surface and the presence of inflammatory mediators in the tear film during contact lens wear. Methods The literature on contact lens discomfort that relates to signs of inflammation was searched. Reference was paid to the cardinal signs of inflammation (pain, heat, redness, and swelling) as well as the appearance of inflammatory mediators in the tear film during contact lens wear. Results Contact lens wear does induce discomfort, which is a mild form of pain, and wearing of lenses can induce increases in limbal and conjunctival redness. However, there is little evidence for a direct relationship between limbal or conjunctival redness and contact lens discomfort. Contact lenses may increase the temperature of the ocular surface by a small amount (≤2.1°C). Corneal or conjunctival swelling has not been associated with contact lens discomfort. Complement or kinin breakdown products or histamine in tears are not associated with contact lens discomfort. Cytokines are generally not related to discomfort, although nerve growth factor levels were increased in tears of symptomatics in one report. The presence of degraded lipids, leukotriene B4 and peroxidation products, and the enzyme secretory phospholipase A2 in tears has been associated with contact lens discomfort, and this area is worthy of further research. Conclusions There have been only a few studies that have investigated a role for inflammation in contact lens-induced discomfort, and the strongest associations have been found with lipid degradation processes.

Studies indicate that contact lens (CL) discontinuation mostly occurs because of dryness and discomfort symptoms. This study aimed to investigate relationships between changes in the concentration of tear inflammatory mediators with subjective comfort ratings with CL wear and no contact lens wear between morning and evening.Forty-five subjects collected tears twice daily in the morning and in the evening with or without lenses. Comfort was rated subjectively on a scale from 1 to 100 (where 100 was extremely comfortable) just before each tear collection. Tear samples were assayed for complement components (C3 and C3a), leukotriene B4 (LTB4), secretory phospholipase A2 (sPLA2), secretory immunoglobulin A (sIgA), and bradykinin using commercially available immuno-based assay kits.Comfort ratings showed a statistically significant decline from morning to evening both with CL (89.0±10.1 AM vs. 76.7±15.2 PM; P0.001) and without CL (89.1±10.2 AM vs. 84.2±12.6 PM; P0.005) wear. The decline was steeper with lens wear (P0.001). Bradykinin and sPLA2 levels did not change between morning and evening or with CL wear (P0.05). Leukotriene B4 levels were slightly higher in CL (CL 43.4±12.6 pg/ml vs. No CL 39.4±13.4 pg/mL; P=0.034), whereas the concentration of LTB4, C3, C3a, and sIgA dropped by the end of the day in the presence or absence of lens wear (P0.001). For most mediators, tear levels were not correlated with comfort ratings in any of the conditions. Leukotriene B4 had a higher concentration in the evening, and when measured as a ratio to sIgA, there was a trend for increased concentration of this mediator during CL wear.Although specific mediators showed changes from morning to evening with and without lens wear, most of these were not correlated with subjective comfort ratings in lens wear. The only mediator that showed an increase in concentration during the day and during lens wear was LTB4, and further studies on this mediator are warranted.

To investigate the ability of protamine, alone or in combination with other antimicrobial agents, to kill bacteria and fungi associated with contact lens-related keratitis.The International Organization for Standardization 14729:2001 procedure was used to test the antimicrobial activity of solutions of protamine (23-228 μM) with and without polyhexamethylene biguanide (PHMB) and ethylenediamine tetra-acetic acid (EDTA). The recommended ISO panel of microbes along with six clinical isolates was tested. The effect of increasing sodium chloride concentration on the antimicrobial activity was also assessed. The cytotoxicity of the final protamine/EDTA/PHMB solution was measured using ISO 10993-5 standard assays.Protamine gave a dose-dependent antimicrobial effect, with the highest effect for most strains being at 228 μM (≥6 log reductions of viable bacteria and ≥1 log reduction of viable fungi). Addition of EDTA and PHMB increased the antimicrobial effect for all strains except Pseudomonas aeruginosa ATCC6538, which had optimum activity (≥6 log inhibition) even in protamine alone. The optimum antimicrobial activity of all microbes was achieved in 0.2% sodium chloride, but even in 0.8% sodium chloride, the activity met or exceeded the ISO standard (3 log reductions for bacteria and1 log reduction for fungi). None of the formulations was cytotoxic to mammalian cells.This study highlights the potential for protamine to be used for the development of effective multipurpose disinfection solutions. Further investigations such as stability, compatibility with contact lenses, and in vivo toxicity are warranted.

The failure of many antibiotics in the treatment of chronic infections caused by multidrug-resistant (MDR) bacteria necessitates the development of effective strategies to combat this global healthcare issue. Here, we report an antimicrobial platform based on the synergistic action between commercially available antibiotics and a potent synthetic antimicrobial polymer that consists of three key functionalities: low-fouling oligoethylene glycol, hydrophobic ethylhexyl, and cationic primary amine groups. Checkerboard assays with Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli demonstrated synergy between our synthetic antimicrobial polymer and two antibiotics, doxycycline and colistin. Coadministration of these compounds significantly improved the bacteriostatic efficacy especially against MDR P. aeruginosa strains PA32 and PA37, where the minimal inhibitory concentrations (MICs) of polymer and antibiotics were reduced by at least 4-fold. A synergistic killing activity was observed when the antimicrobial polymer was used in combination with doxycycline, killing >99.999% of planktonic and biofilm P. aeruginosa PAO1 upon a 20 min treatment at a polymer concentration of 128 μg mL -1 (4.6 μM) and doxycycline concentration of 64 μg mL -1 (133.1 μM). In addition, this synergistic combination reduced the rate of resistance development in P. aeruginosa compared to individual compounds and was also capable of reviving susceptibility to treatment in the resistant strains.

We are familiar with the use of various ophthalmic biomaterials such as intraocular lenses and contact lenses. However, all these intraocular, periocular, and orbital biomaterials are subject to microbial colonisation and infections that are associated with increased morbidity and cost of ophthalmic care. Development of novel antimicrobial materials for the prevention of such infections is critical to safeguarding vision. In order to achieve this, several antimicrobial strategies have emerged and these are described in this chapter.

Aims Patients with chronic kidney disease (CKD) in type 2 diabetes typically manifest with severe peripheral neuropathy. Corneal confocal microscopy is a novel technique that may serve as a marker of nerve injury in peripheral neuropathy. This study examines the changes that occur in corneal nerve morphology as a result of peripheral neuropathy due to renal dysfunction in people with type 2 diabetes. Methods Sixty-two participants (mean age, 62 ± 12 years) with type 2 diabetes and 25 age-matched healthy controls underwent a comprehensive assessment of neuropathy using the total neuropathy score (TNS). The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fiber length, fiber density, branch density, total branch density, nerve fractal dimension, inferior whorl length and inferior whorl nerve fractal dimension were quantified. Based on the eGFR, participants were classified into those with diabetic CKD (eGFR Results Participants with diabetic CKD had significantly lower corneal nerve fiber density (P = 0.037), length (P = 0.036) and nerve fractal dimension (P = 0.036) compared to those without CKD. Multiple linear regression analysis revealed that reduced corneal nerve fiber density (s coefficient = 0.098, P = 0.017), length (s coefficient = 0.006, P = 0.008) and nerve fractal dimension (s coefficient = 0.001, P = 0.007) was associated with low eGFR levels when adjusted for age, duration of diabetes and severity of neuropathy. Conclusion Corneal confocal microscopy detects corneal nerve loss in patients with diabetic CKD and reduction in corneal nerve parameters is associated with the decline of kidney function.

To explore the changes that occur in the concentrations of substance P (SP) and calcitonin gene-related peptide (CGRP) in tears as a result of corneal denervation and its association with diabetic peripheral neuropathy (DPN).Sixty-three individuals with type 1 diabetes/type 2 diabetes (T1D/T2D) and 34 age-matched healthy controls underwent a detailed assessment of neuropathy using the Total Neuropathy Score (TNS). The concentration of SP and CGRP in tears was measured by enzyme-linked immunosorbent assay. The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fibre length, fibre density, branch density, total branch density, nerve fractal dimension and inferior whorl length were quantified.In T1D, the median [IQR] concentration of SP in tears was significantly reduced in those with DPN, (130 [61-692]pg/mL) compared to both control subjects (763 [405-1555]pg/mL, P 0.01) and in those without DPN (914 [339-1832]pg/mL, P = 0.01); the concentration of CGRP was not changed. In T2D, there was no difference in neuropeptides between participants with diabetes and controls, regardless of neuropathic status. In T1D and T2D, corneal nerve parameters were significantly different between those with DPN or without DPN and controls. A significant correlation was noted between the concentration of tear film SP and TNS in T1D (r = -0.49; P 0.001) and corneal nerve fibre density (r = 0.45; P 0.001). The concentration of tear film CGRP was correlated significantly with the reduction of corneal nerve fibre density (r = 0.41; P = 0.01) in T1D.Tear film SP may provide a potential non-invasive biomarker for assessing neuropathy in T1D.

SIGNIFICANCE Microblepharon exfoliation improved eyelid signs and tear film characteristics after a single in-office treatment in symptomatic contact lens wearers. PURPOSE The purpose of this study was to assess the effect of two eyelid hygiene treatments-microblepharon exfoliation and a hypoallergenic foam cleanser (LidHygenix)-on clinical signs of the eyelids, meibomian glands, and tear film in contact lens discomfort. METHODS A randomized, interventional, unmasked, crossover trial was conducted on 30 experienced daily-wear soft contact lens wearers. Assessment of clinical signs of the eyelid margin, meibomian gland morphology and secretion, and tear film biophysical properties was performed (baseline 1), and participants were randomly assigned to receive one of the two treatments (microblepharon exfoliation or foam cleansing using LidHygenix) as a single in-office procedure. Symptoms were evaluated using the Contact Lens Dry Eye Questionnaire-8 immediately after treatment, and assessment of all the study variables was repeated at the follow-up visit 7 to 10 days after treatment. After 28 to 30 days of washout, participants returned for reassessment of the study variables (baseline 2) and were crossed over to receive the alternate treatment. Follow-up was repeated 7 to 10 days after the second treatment. RESULTS Seven to 10 days after treatment with microblepharon exfoliation, symptomatic wearers showed significant improvement in anterior blepharitis (mean difference, 0.60; P = .04), lid wiper staining (0.50; P = .06), and lid-parallel conjunctival folds (0.68, P = .02) along with orifice capping (median difference, 0.65; P < .001), foam (0.90; P < .001), secretion volume (0.69; P < .001), quality (0.74; P < .001), and expressibility (0.49; P = .002), which were also clinically significant changes. However, in tear properties, significant improvements were observed in tear volume (LidHygenix, -1.25 mm; microblepharon exfoliation, -1.62 mm), break-up time (-0.14 seconds; -0.14 seconds), tear evaporation rate without contact lenses (21.52 g m h; 45.43 g m h), and lipid layer thickness (-20.61 nm; -25.13 nm) after both treatments but in symptomatic lens wearers only (P < .05). CONCLUSIONS Microblepharon exfoliation improved eyelid signs and tear film characteristics in symptomatic contact lens wearers after a single in-office treatment.

Exploratory analysis to assess the association of single nucleotide polymorphisms (SNPs) in the interleukin (IL) 10 and IL-17 genes with severity of contact lens keratitis.This was a retrospective case control study of 88 contact lens keratitis cases (25 severe) and 185 healthy contact lens wearers recruited from studies conducted at Moorfields Eye Hospital and in Australia-wide during 2003-2005. Buccal swab samples were collected on Whatman FTA cards and mailed by post for DNA extraction and SNP genotyping. IL-10 (rs1800871; rs1800896; rs1800872) and IL-17 (rs1800871; rs1800896; rs1800872) SNPs were screened by pyrosequencing. Genetic association analyses were performed via Cochran-Armitage trend tests and logistic regression models using PLINK software.None of the SNPs tested showed evidence of association with severity of contact lens keratitis at P 0.05. Nevertheless, minor allele G in SNP rs2397084 of the IL-17F gene was associated with increased risk of severe MK, with OR=2.1 (95% CI=0.9-4.8, P = 0.066).Our study cannot exclude with confidence that genetic variation in the IL-17 F proinflammatory cytokine is associated with more severe outcomes of MK. However, there is general body of information that the IL-17 pathway is important in the mechanisms of MK. Studies with larger power and the expanded array of laboratory tools will elucidate the exact role of IL-17 in MK.

This article summarises research undertaken since 1993 in the Willcox laboratory at the University of New South Wales, Sydney on the tear film, its interactions with contact lenses, and the use of tears as a source of biomarkers for ocular and non-ocular diseases. The proteome, lipidome and glycome of tears all contribute to important aspects of the tear film, including its structure, its ability to defend the ocular surface against microbes and to help heal ocular surface injuries. The tear film interacts with contact lenses in vivo and interactions between tears and lenses can affect the biocompatibility of lenses, and may be important in mediating discomfort responses during lens wear. Suggestions are made for follow-up research.

Microbiomes in the built environment is an emerging topic of high-relevance, as biodeterioration and biodegradation of porous and polymer materials may be major public health risk factors. Epidemiological studies have confirmed indoor airborne microorganisms and their metabolites cause significant toxic immune reactions, with clinical effects associated with more than 60% of occupants’ chronic infections. The present study reports the potential inhibitory effect on microbial and fungal colonization of hydrothermal hot-compression for the manufacture of a series of novel cellulose-based panels engineered for insulating building applications. This method was examined as it is a green manufacturing technique which simultaneously self-bonds the cellulose fibres, as well as potentially having an anti-microbial effect. The technique renders the novel materials non-toxic, additive-free, biodegradation resistant, as well as increasing the recyclability potential of the materials at their end-of-life. Prototypes were formulated from three cellulosic materials sourced from complex post-consumer coffee industry heterogeneous waste stream ─jute textile, paper cups, and coffee grounds─ holding initially high-levels of microbiological contamination. The raw materials were characterized with Infrared Spectroscopy (FTIR) and Scanning Electronic Microscopy (SEM). Microbial species were identified using culture-dependent and culture-independent DNA quantitative methods for the raw materials, as well as the processed panels. The experimental results confirmed a high-level of bacterial and fungal contamination with ubiquitous environmental bacteria such as Bacillus, Burkholderia, and Stenotrophomonas species for the Jute textile and Paper cup fibres. However, the microbes were minimized or non-detectable for all three processed panel samples. This promising result demonstrates that complex cellulosic waste materials can be converted to low-microbial biomass potential industrial feedstock for the green manufacturing of building materials.

Ocular discomfort is among the main causes of contact lens wear discontinuation. This study investigated the association between subjective ocular comfort ratings and diurnal changes in tear protein concentrations with and without contact lens wear.The study was a prospective, open-label, single-group two-staged investigation. Basal tears were collected from 30 experienced contact lens wearers twice a day (morning and evening) using a noninvasive method without lens wear (stage 1) and during wear of Etafilcon A contact lenses (stage 2) for 7 to 10 days. Subjects rated their ocular comfort on a scale of 1 to 100 (with 100 as extremely comfortable) at each time of tear collection. Tears were analyzed using liquid quadrupole mass spectrometry in conjunction with selected reaction monitoring (SRM) method.End-of-day comfort was reduced when wearing lenses (87.8 ± 14.3 AM vs. 79.2 ± 16.6 PM) compared to no lens wear (88.3 ± 12.6 AM vs. 84.7 ± 13.3 PM) (AM vs. PM, p0.05). A greater reduction in comfort over the day was seen during lens wear (p0.01). The concentration of prolactin-induced protein increased from morning to evening in both stages (mean ± SD; 0.08 ± 0.04 mg/ml, AM vs. 0.09 ± 0.05 mg/ml, PM, p0.05). There was no change in the concentration of lactoferrin (1.20 ± 0.77 mg/ml), lysozyme (2.11 ± 1.50 mg/ml), lipocalin 1 (1.75 ± 0.99 mg/ml), or proline-rich protein 4 (0.80 ± 0.49 mg/ml). The prolactin-induced protein concentration was negatively associated with discomfort levels in tears (p0.05, r = -0.29).Only the absolute concentration of prolactin-induced protein correlated with subjective comfort ratings. Taking into consideration that prolactin-induced protein can be associated with disruption in water transport in lacrimal glands, our findings may indicate that changes to aqueous secretion are associated with contact lens discomfort.

Purpose Our aim was to quantitate day-to-day changes in the tear and meibum lipid profile of individual subjects in a pilot study of healthy humans. Methods Matched tear and meibum samples were obtained from four subjects on three consecutive days. Quantitative lipid profiles of human basal tears and meibum were compared using multivariate analysis by principal components. Results Substantial differences in the lipid profile between subjects were observed, while lipid profiles were steady across the three consecutive days of sampling. Multivariate principal component analysis demonstrated that lysophosphatidylcholine was the largest variant lipid class between subjects in tears, while wax esters comprised the most variation between subjects in meibum secretions. Conclusion Interday variability is shown to be much smaller than interpatient variability, suggesting that tears and meibum subjects both have unique profiles in humans.

Coronaviruses including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, also known as 2019-nCoV especially in China) replicate and divide in host cells. During this they are partly hidden from the innate immune responses although inflammatory consequences of viral replication still occur. We propose that anti-inflammatory antiviral prostaglandins may not only restrict viral replication but also prevent inflammatory responses in the lungs and other vital organs that are known to be part of the immuno-pathogenesis of coronavirus disease-19 (COVID-19). The combination of anti-inflammatory antiviral prostaglandins with interferons may lead to the clearance of viruses inside growth-restricted infected cells. However, further experimental studies and clinical trials should be conducted to evaluate the safety and efficacy of these possible therapies.

Antimicrobial resistance is a multifaceted crisis, imposing a serious threat to global health. The traditional antibiotic pipeline has been exhausted, prompting research into alternate antimicrobial strategies. Inspired by nature, antimicrobial peptides are rapidly gaining attention for their clinical potential as they present distinct advantages over traditional antibiotics. Antimicrobial peptides are found in all forms of life and demonstrate a pivotal role in the innate immune system. Many antimicrobial peptides are evolutionarily conserved, with limited propensity for resistance. Additionally, chemical modifications to the peptide backbone can be used to improve biological activity and stability and reduce toxicity. This review details the therapeutic potential of peptide-based antimicrobials, as well as the challenges needed to overcome in order for clinical translation. We explore the proposed mechanisms of activity, design of synthetic biomimics, and how this novel class of antimicrobial compound may address the need for effective antibiotics. Finally, we discuss commercially available peptide-based antimicrobials and antimicrobial peptides in clinical trials.

Early diagnosis of clinical markers of contact lens discomfort can help clinicians set realistic expectations and monitor and provide prophylactic management for contact lens wearers.The purpose of this study was to evaluate the potential of eyelid- and tear film-related clinical markers to be used as predictive factors for diagnosing discomfort in contact lens wearers.A cross-sectional study was performed on 30 contact lens wearers (6 male, 24 female) with median age of 23 years (range, 18 to 41 years). Eyelid signs and tear film characteristics were evaluated during a single visit, and subjects completed the Contact Lens Dry Eye Questionnaire to evaluate ocular discomfort. Area under the curve (AUC) statistics and sensitivity and specificity values from receiver operating characteristic curves were analyzed to evaluate the predictive potential of clinical signs in discriminating symptoms of contact lens discomfort.The presence of foam at meibomian gland orifices (AUC, 0.944; P.05; sensitivity0.7), meibomian gland secretion volume (AUC, 0.935; P.05; sensitivity0.7), quality (AUC, 0.969; P.05; sensitivity0.7), and expressibility (AUC, 0.933; P.05; sensitivity0.7) were significant and strong predictors of discomfort in lens wear. Tear evaporation rates with (AUC, 0.779; P.05; sensitivity0.7) or without contact lenses (AUC, 0.788; P.05; sensitivity0.7), palpebral conjunctival roughness (AUC, 0.859; P.05; sensitivity0.7), palpebral conjunctival staining (AUC, 0.817; P.05; sensitivity0.7), palpebral conjunctival hyperemia (AUC, 0.746; P.05; sensitivity0.7), meibomian gland orifice capping (AUC, 0.873; P.05; sensitivity0.7), pouting (AUC, 0.891; P.05; sensitivity0.7), and lid-parallel conjunctival folds (AUC, 0.770; P.05; sensitivity0.7) were other acceptable discriminators of symptoms of discomfort during contact lens wear. An equation was developed to identify symptomatic from asymptomatic lens wearers based on the significant predictors: Symptom discriminant function score = 3.378 (meibomian gland secretion grade) + 0.224 (meibomian gland morphology grade) + 0.61 (tear evaporation rate without contact lenses) + 0.439 (lid-parallel conjunctival folds grade) - 0.346 (palpebral conjunctival health grade) - 4.625.This study demonstrated that clinical signs related to meibomian gland secretions and morphology, tear evaporation, lid-parallel conjunctival folds, and palpebral conjunctival health may successfully predict symptoms of discomfort in contact lens wearers.

AIM A series of proof-of-principle extended wear (EW) contact lens studies were conducted to assess what effect different interventions had on adverse events (AEs). Comparative analysis of AEs across studies was conducted to determine whether some interventions were more effective at reducing inflammatory AEs. METHOD Multiple logistic regression analysis of AEs from 30-day EW studies each with a different intervention including (1) nightly replacement (NR) of lenses, (2) morning replacement (MR) of lenses, (3) instillation of prophylactic antibiotic drops (AB) each morning/evening, (4) daily lens cleaning (LC) each morning. All studies conducted at the same site using same lens type (lotrafilcon A) and EW schedule. RESULTS Comparison of the different interventions to the individual control groups showed no difference in significant corneal infiltrative event (CIE) or mechanical events. Replacing lenses nightly, during an EW schedule, had the highest incidence of significant CIEs (4.9% [NR] vs. 2.5% [MR] vs. 1.8% [AB] vs. 0% [LC]); however, adjusted logistic regression analysis of the combined control data compared with the individual interventions showed no difference in significant CIEs (P=0.086) or mechanical AEs (P=0.140). CONCLUSIONS Replacing lenses each night seemed to be inferior compared with the other interventions of replacing lenses each morning, daily lens cleaning, and daily antibiotic drop instillation during EW. The results of the collective studies and additional analysis suggest that overnight wear of contact lenses seems to create an adverse environment that remains, despite the various interventions intended to improve this adverse environment.

We report on the development of a novel optical imaging technique for visualizing tear film lipid using scandium doped silicone quantum dots with varying surface chemistries; lipophilic and hydrophilic.

To assess the association between the levels of lens case contamination and lens wearers' hygiene behaviors.Contact lens wearers were surveyed for information on wearer demographics and contact lens hygiene behavior. Microbial analysis of lens cases was performed. Multivariate analysis was used to identify factors associated with contact lens storage case contamination.One hundred nineteen contact lens wearers responded. The mean (±SD) age of the participant was 32 (±1) years (range, 18 to 69 years). Seventy percent of the participants were female. Sixty-six percent of lens cases were contaminated (median, 25; range, 0 to 10⁷ colony-forming units [CFUs]). In the multivariate analysis, washing hands with soap and water (1.8 ± 2.0 log10 CFU/case) rather than just water or no washing was associated with lower levels of lens case contamination (2.4 ± 2.1 log10 CFU/case; p = 0.005). Lens cases received wet had higher levels of contamination than dry cases (1.5 ± 1.5 vs. 2.4 ± 2.5 log10 CFU/case; p = 0.015). Mismatching lens case and disinfecting solution was a risk factor for lens case contamination (p = 0.019). Lens wearers who had more than 2 years of wearing experience had higher levels of contamination than those who had less than 2 years of wearing experience (2.1 ± 2.1 vs. 1.1 ± 1.5 log10 CFU/case; p = 0.04).Major factors that can reduce lens case contamination were washing hands with soap and water, air-drying lens cases, and matching of the disinfecting solution with lens case (i.e., from the same manufacturer). This information is beneficial when advising lens wearers in clinical practice.

Established reusable contact lens (CL) wearers show higher tear inflammatory cytokine concentrations and greater conjunctival metaplasia in the region covered by standard soft CLs. The balance of proinflammatory to anti-inflammatory cytokines, but not individual tear cytokine concentrations, was associated with self-reported CL discomfort.Daily disposable (DD) lenses are often used to improve CL discomfort, but the effect on ocular inflammatory responses has not been fully investigated. This study aimed to compare the concentrations of tear cytokines and conjunctival cell morphology in healthy habitual DD and reusable soft CL wearers.Thirty-six established daily CL wearers, including 14 DD and 24 reusable wearers, were enrolled. Symptoms and ocular surface integrity were evaluated. The concentration of tear cytokines (interleukin 1β [IL-1β], IL-6, IL-10, IL-12(p70), IL-17A, and tumor necrosis factor α) were determined using Multiplex assays. The ratios of proinflammatory and anti-inflammatory cytokines were calculated. Impression cytology was performed on the conjunctiva, and goblet cell density and epithelial squamous metaplasia were quantified. Differences in variables by CL replacement schedules and the associations between variables were analyzed.Reusable CL wearers had higher concentrations (in pg/mL) of IL-1β (26 ± 7 vs. 16 ± 11), IL-6 (42 ± 14 vs. 25 ± 20), IL-10 (83 ± 23 vs. 49 ± 36), IL-12(p70) (145 ± 44 vs. 91 ± 68), IL-17A (93 ± 26 vs. 54 ± 44), and tumor necrosis factor α (312 [171 to 468] vs. 189 [6 to 447]) (all P.01) and greater conjunctival metaplasia in the region covered by CLs (0.7 [0.2 to 1.6] vs. 0.4 [0.04 to 1.2], P = .01) compared with DD wearers. There was a positive association between CL discomfort and ratios of IL-1β to IL-10 and IL-12(p70) to IL-10 (ρ = 0.42 and ρ = 0.33, P.05).Higher ocular inflammatory responses, as indicated by higher tear cytokine concentrations and higher conjunctival epithelial metaplasia, were found in reusable CL wearers than in DD CL wearers. The balance of proinflammatory and anti-inflammatory cytokines may be helpful to assess the inflammatory status of the eye.