Search

Abstract omitted due to copyright. [ABSTRACT FROM AUTHOR]

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP-lowering is the most important treatment strategy, mostly through topical eyedrops. Well-functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative-free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP-lowering eye drops on the meibomian glands., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample., Design: Cross-sectional study., Setting: Community-dwelling cohort., Participants: Twins from the TwinsUK cohort PRIMARY AND SECONDARY OUTCOME MEASURES: We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing., Results: In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance., Conclusion: Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Dry eye disease (DED) is a highly prevalent condition, resulting in reduced quality of life, lower participation in social life and impaired work efficiency. Hydroxypropyl methylcellulose (HPMC) is a cellulose-based viscosity-enhancing agent and is one of the most popular therapeutic ingredients in artificial tears. This review aims to evaluate the literature on the efficacy and safety of HPMC used in the treatment of DED. Literature searches were conducted in PubMed and Cochrane CENTRAL. A total of 28 clinical trials from 26 publications are included in this review, including 21 clinical intervention studies evaluating the effect of HPMC treatment over time and seven single instillation studies evaluating the short-term physical and symptomatic effects of HPMC after drop-instillation. The duration of clinical intervention studies ranged from 2 weeks to 5.5 months. DED severity ranged from mild to severe. Drop frequency ranged from two to up to 16 drops per day. HPMC concentration in artificial tears ranged from 0.2% to 0.5%. No major complications or adverse events were reported. Artificial tears containing HPMC were effective at improving symptoms and some signs of DED. However, combination drops with HPMC plus other therapeutic ingredients seem more effective than HPMC alone. HPMC appears to be equally effective or inferior to hyaluronic acid (HA). There is no evidence of superiority or inferiority to either carboxymethylcellulose (CMC) or polyethylene glycol 400/propylene glycol (PEG/PG). No single study explained the choice of drop frequency or HPMC concentration. More well-designed studies are needed to determine an evidence-based standard for HPMC treatment, including drop frequency, concentration and molecular weight for different DED severity and subgroups., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Dry eye disease is a highly prevalent condition, which can substantially impair quality of life, work productivity, and vision. It is considered an inflammatory disease and the most common cause is meibomian gland dysfunction. Despite many treatment alternatives being available, including artificial tears, warm compresses, antibiotics, and anti-inflammatory therapy, lasting treatment effects are rare. Over the last two decades, intense pulsed light therapy, after being well established in dermatology, has been gradually introduced to the field of ophthalmology to treat meibomian gland dysfunction. The purpose of the current article is to critically review the clinical studies assessing the use of intense pulsed light to treat meibomian gland dysfunction published to date. The vast majority of the included studies demonstrated improved symptoms and signs, although the degree of efficacy and its duration varied greatly depending on concomitant treatment, number of treatment sessions, and other factors. Several possible mechanisms of action concerning disease propagation and treatment efficacy are discussed. There is still a need for larger, randomised, longitudinal studies to define the most efficacious treatment regime and to predict which patients may benefit the most. More studies are needed on implementing biochemical analyses and machine learning algorithms. Such studies may prove beneficial in predicting treatment effects, defining optimal treatment regimens, and furthering our understanding of the mechanisms of action., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

A particularly conspicuous morphological feature in chalcidoid wasps are strikingly modified legs present in both males and females. It evolved convergently multiple times on either fore or hind legs implying strong evolutionary pressure and a prominent function in the wasps' life history. We investigate the external and internal morphology of the modified legs of five species of chalcidoid wasps representing four families (Ooderidae, Heydeniidae, Chalcididae, and Leucospidae), using light microscopy, scanning electron microscopy and micro computed tomography. We aimed to identify shared characteristics as well as differences between genera/species, leg pairs and sexes and to draw first conclusions about the shared or different functions. All species and sexes share the same general leg morphology, with enlarged femur, curved tibia and a huge flexor tibiae muscle. However, there are also genus/species-specific differences such as distinctive spine-like setae on the femur of Oodera spp., or leg pair-specific differences in the position of the extensor tibiae muscle. Shared characteristics imply a common primary function in which strong forces are required to pull the tibia against the femur while differences imply different secondary functions. Both primary and secondary functions have yet to be revealed beyond informed speculations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dry eye disease (DED) is a highly prevalent and debilitating condition. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has a long history as a safe and effective DED treatment. HA is frequently used as a comparator when assessing other topical DED treatments. This study aims to summarise and critically evaluate the literature describing all isolated active ingredients that have been directly compared with HA in the treatment of DED. A literature search was conducted in Embase using Ovid on the 24th of August 2021 and in PubMed including MEDLINE on the 20th of September 2021. Twenty-three studies met the inclusion criteria, 21 of which were randomised controlled trials. Seventeen different ingredients representing six treatment categories were compared with HA treatment. Most measures showed no significant difference between treatments, suggesting either equivalency of treatments or that studies were underpowered. Only two ingredients were represented in more than two studies; carboxymethyl cellulose treatment appears equivalent to HA treatment, while Diquafosol treatment appears superior to HA treatment. Drop-frequency varied from one to eight drops daily. No single study explained the choice of drop frequency. Nine studies used a HA concentration of 0.1% which may be below therapeutic levels. Nine studies reported using preserved formulations, six of them with differences in preservatives between the compared groups. Thirteen studies were financially linked to industry. No major complications were reported. Studies were not designed to find differences in treatment effects for different types or severities of DED. HA is a good comparator treatment when assessing other DED treatments, although consensus after decades of use is still lacking for best choice of concentration, molecular weight and drop tonicity. Well-designed studies are needed to determine an evidence-based standard for HA treatment to be used as comparator., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Accurate diagnosis of dry eye disease (DED) is challenging, and even today there is no gold standard biomarker of DED. Hypothesis-free global metabolomic studies of tears from DED patients have great potential to discover metabolites and pathways affected in the pathophysiology of DED, and to identify possible future biomarkers. These metabolites and biomarkers could be important for diagnosing and monitoring disease as well as for new therapeutic targets and strategies. As DED is associated with dry mouth, this study aimed to perform metabolomic analyses of tears and saliva from patients with decreased tear film break-up time but normal Schirmer test, and age-matched controls with both tear production and stability within physiological range. We applied strict inclusion criteria to reduce sampling bias in the metabolomic analyses and selected only age-matched females with Schirmer test values between 10-15 mm/5 min. The tear film analysis arm included 19 patients (with tear film break-up time 0-5 s) and 12 controls (with tear film break-up time 10-30 s), while the salivary analysis arm consisted of a subset which included 18 patients and six controls. Metabolomic analyses were performed using liquid chromatography and high-resolution mass spectrometry. Analyses using a global database search detected a total of 56 metabolites in tear samples that were significantly different between the groups. Of these, several have known associations with DED. These metabolites are present in meibum and have anti-oxidative characteristics or associations with the ocular microbiome, and altered concentrations suggest that they may play a significant role in DED associated with decreased tear film stability. In saliva, hypotaurine levels were lower among patients with tear film instability. In this pilot study, we found different levels of several metabolites in patients with decreased tear film break-up time that may have associations with DED. Future studies are required to replicate our findings and clarify the exact roles of these metabolites.

Purpose: To investigate the hypothesis that a Mediterranean diet is associated with a lower risk of having dry eye disease (DED) in the general population., Methods: DED was assessed using the Women's Health Study (WHS) dry eye questionnaire in 58,993 participants from the Dutch Lifelines Cohort with complete available dietary data (20-94 years, 60% female). Level of adherence to a traditional Mediterranean diet was assessed using the modified Mediterranean Diet Score (mMDS). High-sensitivity C-reactive Protein (hsCRP) was included as a marker of whole-body inflammation. Logistic regressions were used to examine the relationship between WHS-defined DED and mMDS, corrected for age, sex, BMI, education, income, and 48 potentially confounding comorbidities. The association between mMDS and hsCRP, and hsCRP and DED, was further explored in separate regressions., Results: Of all participants, 9.1% had DED. In contrast to the hypothesis, higher mMDS levels were associated with greater odds of DED, corrected for demographics, smoking status, BMI, and comorbidities (OR 1.034, 95%CI: 1.015 to 1.055, P = 0.001). Moreover, there was a highly significant relationship between increasing mMDS and lower circulating hsCRP levels; however, there was no significant relationship between hsCRP and DED., Conclusions: Stronger adherence to a Mediterranean diet does not appear to be associated with lower odds of having DED in the general population. Furthermore, there was no association between hsCRP and DED in this study. However, the previously described link between a Mediterranean diet and lower hsCRP was confirmed in this large population-based study., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials., Competing Interests: Declaration of competing interest Maria Markoulli: Alcon (F), CooperVision (F). Sumaya Ahmad: None. Jayashree Arcot: None. Reiko Arita: (P), Alcon (F), Novartis (F), Senju Pharmaceutical (F), Santen (F), Rohto Pharmaceutical (F), Johnson & Johnson (F), Lumenis (F), Inami (F), Topcon (C). Jose M Benitez-del-Castillo: Alcon (C), Allergan (C), Angelini (C), Brill Farma (C), Esteve (F), GSK (C), Horus (C), Lumenis (F), Novartis (C), Santen (F), Thea (F). Barbara Caffery: Azura (F), Santen (C), VTI (F), Dompe (C). Laura Downie: Alcon Laboratories (F), Azura Ophthalmics (F), CooperVision (F), Kedalion Therapeutics (F), Medmont International (F), Novartis (F), Seqirus (F). Katie Edwards: None. Judith Flanagan: None. Marc Labetoulle: Alcon (F), Allergan (F), Baush & Lomb (F), DMG (F), Dompe (F), GSK (F), Horus (F), MSD (F), Novartis (F), PHE (F), Quantel (F), Santen (F), Shire (F), Sifi (F), Topivert (F), Théa (F). Stuti Misra: None. Malgorzata Mrugacz: None. John Sheppard: None. Sumeer Singh: None. Jelle Vehof: Alcon (C), Tramedico (C), Santen (C), Théa Pharma (C), Horus Pharma (C). Piera Versura: None. Mark Willcox: Alcon (F), Allergan (F), CooperVision (F), Johnson and Johnson Vision (F), Ophtecs (C, F). Jillian Ziemanski: None. James Wolffsohn: AOS (C), Aston Vision Sciences (S), Bausch & Lomb (C), Alcon (C,F), Allergan (F), CooperVision (C,F), CSIDryEye (C), Eyoto (S), Johnson & Johnson Vision (F), Rayner (F), M2C Pharmaceuticals (C,F), Medmont (C), Novartis (C,F), NuVision (C,F), Santen (C), Scope Ophthalmics (C,F), Théa (C,F), Topcon (F), The Eye Doctor (F), Wolffsohn Research Limited (S)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To build a questionnaire-based myopia proxy and to validate the proxy by confirming its association with educational attainment and a Polygenic Risk Score (PRS) for myopia., Methods: Data were collected between 2014 and 2017 from 88 646 Dutch adults from the LifeLines Cohort. First, we performed principal component analysis (PCA) to responses of five refraction-status questions. Second, we measured the refractive state in a subset of LifeLines participants (n=326) and performed logistic regression using myopia (mean spherical equivalent <-0.5 D) as a dependent variable and the principal components (PCs) as independent variables. We identified specificity, sensitivity and the classification threshold. Third, the classification equation was applied to the remaining LifeLines participants. The value of the proxy was then explored by calculating its association with educational attainment and a PRS of myopia., Results: A total of 77 096 participants (58.1% women) were eligible for the PCA. The first two PCs had a specificity of 91.9% (95% CI 87.8% to 95.4%) and a sensitivity of 90.4% (95% CI 84.3% to 96.4%) for myopia. The area under the receiver operating characteristic curve was 95.0% (95% CI 92.2% to 97.8%). The age-standardised prevalence of proxy-inferred myopia was 33.8% (95% CI 33.4% to 34.3%). Compared with low education level, the ORs of proxy-inferred myopia were 1.66 (95% CI 1.58 to 1.74, p=5.94×10 -90 ) and 2.54 (95% CI 2.41 to 2.68, p=4.04×10 -271 ) for medium and high education levels, respectively. Similarly, individuals at the top 10% of PRS (vs lower 90%) had an OR of 2.18 (95% CI 1.98 to 2.41, p=6.57×10 -56 ) for proxy-inferred myopia, whereas those at the highest decile had an OR of 4.51 (95% CI 3.9 to 5.21, p=1.74×10 -89 ) when compared with the lowest decile., Conclusion: Self-administered refractive error-related questions could be used as an effective tool to capture proxy-inferred myopic cases in a population-based setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed., Purpose: To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment., Methods: Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included., Results: The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 °C and 47 °C. Towels heated to around 45 °C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies., Conclusion: Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Morten Schjerven Magno: Nothing to disclose. Jonatan Olafsson: Nothing to disclose. Marie Beining: Nothing to disclose. Emily Moschowits: Nothing to disclose. Neil Lagali: Nothing to disclose. James S. Wolffsohn is the Chief Scientific Officer of the International Myopia Institute, on the Executive of the Tear Film and Ocular Surface Society and Academic Chair to the BCLA. Honoraria for consultancy received from AtiaVision, Bausch and Lomb, Alcon, CooperVision, Johnson and Johnson Vision, Nevakar, Novartis and Thea Pharmaceutical. He has also received research funding from Alcon, Allergan, Johnson and Johnson Vision, Novartis, M2C Therapeutics, Rayner, and Thea Pharmaceuticals. He is a founder and shareholder in Aston Vision Sciences, Eyoto and Wolffsohn Research ltd. Jennifer P.Craig is founder of the Ocular Surface Laboratory at the University of Auckland, New Zealand which in the last three years has delivered talks for and/or received financial support for research and education in the area of dry eye and ocular surface disease from Alcon, Azura Ophthalmics, E-Swin, Johnson & Johnson Vision, Laboratoires Théa, Manuka Health NZ, Novartis, Resono Ophthalmic, and Topcon. Jelle Vehof has received financial support for talks and education in the area of dry eye and ocular surface disease from Santen. Tramedico, Théa Pharma and Horus Pharma, and is consultant for Santen and Tramedico. Vehofis the Dutch Global Ambassador for Tear Film and Ocular Surface Society (TFOS). Darlene A. Dartt: Nothing to disclose. Tor Paaske Utheim is co-founder and co-owner of The Norwegian dry eye clinic and the Clinic of eye health, Oslo, Norway, which delivers talks for and/or receives financial support from the following: ABIGO, Alcon, Allergan, AMWO, Bausch&Lomb, Bayer, European school for advanced studies in ophthalmology, InnZ Medical, Medilens Nordic, Medistim, Novartis, Santen, Specsavers, Shire Pharmaceuticals and Thea Laboratories. He has served on the global scientific advisory board for Novartis and Alcon as well as the European advisory board for Shire Pharmaceuticals.Utheimis the Norwegian Global Ambassador for Tear Film and Ocular Surface Society (TFOS), a Board Member of the International Ocular Surface Society, a Consultant at the Norwegian Association for the Blind and Partially Sighted, and the Editor-in-Chief of Oftalmolog, an eye journal distributed to all eye doctors in the Nordic region since 1980., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the relationship between dry eye disease (DED) and work functioning, unemployment, absenteeism, and worry about job loss., Methods: DED and unemployment, absenteeism, and 'worry about job loss' were assessed in 71,067 subjects (18-65 years, 60% female) from the Dutch population-based Lifelines cohort using the Women's Health study questionnaire and single-item questions, respectively. Work functioning was assessed in 32,475 participants using the Work role functioning questionnaire 2.0. The relationships between DED and work measures were assessed with logistic regression models, corrected for age, sex, BMI, income, educational level, smoking, and 48 comorbidities., Results: 8.3% of participants had DED and had more impaired work functioning compared to those without DED (49.2% vs 41.1%, OR 1.21, 95% CI 1.10-1.32, corrected for demographics, smoking and 48 comorbidities). DED carried a similar risk of impaired work functioning as rheumatoid arthritis. For participants with highly symptomatic dry eye impaired work functioning was even higher (59.1%) and similar to that of depression. The impaired work functioning seen with increasing symptoms were greater in undiagnosed subjects versus diagnosed subjects (P = 0.03). After correction for comorbidities, DED remained tied to absenteeism and increased worry about job loss, but not unemployment., Conclusion: DED was linked to impaired work functioning and absence, but not unemployment. DEDs impact on work functioning is comparable to that of other severe chronic disorders, and undiagnosed subjects may be more affected. This highlights the importance of recognizing DED as a severe disorder and of screening for dry eye in the workplace to aid with diagnosis and treatment., Competing Interests: Declaration of competing interest No conflicting relationship exists for any author., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Sedentary behavior (SB) has been linked with low-grade systemic inflammation, which could play a role in the development of dry eye disease (DED). This cross-sectional study aims to investigate the association between SB and DED., Methods: We assessed 48,418 participants from the population-based Lifelines cohort (58% female, 18-96 years). Women's Health Study (WHS)-defined DED was the primary outcome. SB was assessed using the Marshall Sitting Questionnaire. The relationship between DED and SB was analyzed using logistic regressions, corrected for age, sex, BMI, smoking status, demographics, and 48 comorbidities. Any potential modifying effect of physical activity (PA) was also assessed, and the analyses were repeated excluding the most computer-intensive domains, investigating SB independent from screen exposure., Results: WHS-defined DED was present in 9.1% of participants. Greater SB was associated with an increased risk of DED (odds ratio (OR) 1.015 per hour/day, 95%CI 1.005-1.024, P = 0.004). The association between SB and DED was only significant for those with less than WHO-recommended PA (OR 1.022, 95%CI 1.002-1.042, P = 0.027), and not in participants meeting WHO's recommendation (OR 1.011, 95%CI 0.999-1.023, P = 0.076). Lastly, when excluding computer-related sitting, the relationship between SB and DED was attenuated, and no longer significant (OR 1.009, 95%CI 0.996-1.023, P = 0.19)., Conclusions: Greater sedentary time was tied to an increased risk of DED, especially for those with lower PA levels than WHO recommendations. However, as there was no significant association when computer-intensive sitting time was excluded, screen use could explain the observed relationship and should be noted as a possible key confounder., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is to test the hypothesis that greater habitual water intake is associated with lower risk of dry eye disease (DED)., Methods: We included 51 551 participants from the population-based Lifelines cohort (mean age = 51.2 years) in this cross-sectional association study. DED was assessed using the Women's Health Study (WHS) dry eye questionnaire. Water intake was calculated from food frequency questionnaires. Logistic regressions were used to analyse the relationship between DED and water intake or 24-h urine volume, corrected for age, sex, body mass index, physical activity, smoking status, education, income, 48 comorbidities, and 15 medication groups. The main outcome measure was WHS-defined DED. Highly symptomatic dry eye and clinical diagnosis of DED were secondary outcomes., Results: In total, 9.1% of the population had WHS-defined DED. Higher water intake was associated with increased prevalence of WHS-defined DED (OR: 1.011 per 100 ml/day, 95% CI: 1.004-1.017, p = 0.003). After excluding those with a clinical diagnosis, greater water intake was still tied to increased risk of having DED symptoms (OR: 1.010 per 100 ml/day, 95% CI: 1.006-1.015, p < 0.001). Higher 24-h urine volumes were also associated with higher risk of WHS-defined DED (OR: 1.010 per 100 ml/day, 95% CI: 1.005-1.015, p < 0.001)., Conclusions: In this large, population-based study, higher water intake was not tied to reduced risk of DED. Rather, it was associated with a modest increased risk of DED. Interventional studies are needed to fully understand the effect of water intake on DED, but this study found no evidence that greater water intake is beneficial for DED., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The aim of this study was to determine the association between caffeine intake and dry eye disease (DED) in the large, population-based LifeLines cohort in the Netherlands., Methods: DED was cross-sectionally assessed in 85,302 participants (59% female participants) using the Women's Health Study dry eye questionnaire. Dietary caffeine was calculated from the intake of coffee, tea, cola, and energy drinks. Logistic regression was used to investigate the relationship between DED and caffeine, correcting for demographic variables, smoking status, alcohol intake, and 48 comorbidities of DED., Results: The mean (SD; range) age of participants was 50.7 years (12.4; 18-96), and 50,339 (59%) were female. The mean (SD) caffeine intake was 285 (182) mg/d. After correcting for demographics, body mass index, smoking status, and alcohol intake, higher caffeine intake was associated with a decreased risk of Women's Health Study-defined DED [odds ratio (OR) 0.971 per 100 mg/d, 95% CI, 0.956-0.986, P < 0.0005]. When additionally adjusting for medical comorbidities, no significant effect was observed (OR 0.985, 95% CI, 0.969-1.001, P = 0.06). Caffeine's effect on DED was similar in male and female participants and independent of sleep quality and stress at work. Decaffeinated coffee intake was significantly associated with an increased risk of DED, when adjusted for caffeinated coffee, demographics, alcohol intake, smoking status, and comorbidities (OR 1.046 per cup/d, 95% CI, 1.010-1.084, P = 0.01). None of the beverages were significantly associated with the risk of DED, when correcting for intake of the other caffeinated beverages, demographics, smoking status, alcohol intake, and all comorbidities., Conclusions: Dietary caffeine intake does not seem to be a risk factor for DED in the general population., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Dry eye disease (DED) is a highly prevalent and debilitating condition affecting several hundred million people worldwide. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan commonly used in the treatment of DED. This review aims to critically evaluate the literature on the safety and efficacy of artificial tears containing HA used in DED treatment. Literature searches were conducted in PubMed, including MEDLINE, and in Embase via Ovid with the search term: "(hyaluronic acid OR hyaluronan OR hyaluronate) AND (dry eye OR sicca)". A total of 53 clinical trials are included in this review, including eight placebo-controlled trials. Hyaluronic acid concentrations ranged from 0.1% to 0.4%. Studies lasted up to 3 months. A broad spectrum of DED types and severities was represented in the reviewed literature. No major complications or adverse events were reported. Artificial tears containing 0.1% to 0.4% HA were effective at improving both signs and symptoms of DED. Two major gaps in the literature have been identified: 1. no study investigated the ideal drop frequency for HA-containing eyedrops, and 2. insufficient evidence was presented to recommend any specific HA formulation over another. Future investigations assessing the optimal drop frequency for different concentrations and molecular weights of HA, different drop formulations, including tonicity, and accounting for DED severity and aetiology are essential for an evidence-based, individualized approach to DED treatment., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described., Purpose: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED., Methods: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated., Findings: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development., Conclusion: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Teleost fishes show an enormous diversity of parental care, ranging from no care to viviparity with maternal provisioning of embryos. External brooders carry their developing eggs attached to their bodies. This requires the formation of novel morphological structures to support attachment. The pelvic brooding ricefish Oryzias eversi evolved such a structure, called the "plug." The plug anchors attaching filaments from the fertilized eggs inside the female reproductive system, allowing the female to carry the embryos until hatching. Using histological sections and µ-computed tomography scanning, we show that the plug is formed by several types of interstitial cells, blood capillaries, and collagen fibrils that encapsulate the end of the attaching filaments in the anterior part of the gonoduct. Even 15 days after the loss of the protruding attaching filaments, the plug remains. In addition, the developed plug contains multinucleated giant cells that are derived from fusing macrophages. We thus hypothesize that the ricefish plug, which is vital for egg attachment in O. eversi, evolved due to an inflammatory reaction. We assume that it forms similar to a foreign body granuloma, as a reaction to irritation or injury of the gonoduct epithelium by the attaching filaments. Our study further corroborates that pelvic brooding entails a complex set of adaptations to prolonged egg-carrying in the female reproductive system. During brooding, for instance, ovulation in the ovary is suppressed and the anterior part of the gonoduct is characterized by an intricate, recessed folding., (© 2022 The Authors. Journal of Morphology published by Wiley Periodicals LLC.)

Background: Dry eye disease (DED) is a common cause of ocular pain and discomfort. Dry eye disease (DED) stems from a loss-of-tear film homeostasis and is frequently seen in video display terminal (VDT) users. Video display terminal (VDT) use reduces blink rates and increases incomplete blinks, leading to tear film instability and ocular inflammation, promoting DED., Purpose: To assess and evaluate the methods for preventing VDT-associated DED and ocular discomfort., Methods: Studies were found using PubMed and Embase with the search terms: (digital visual terminal* OR computer use OR screen use OR smartphone OR display OR visual display terminal* OR computer vision syndrome OR tablet OR phone OR screen time) AND (dry eye OR DED)., Results: Thirty-one relevant articles were found. Ten described single-visit studies, whereas 21 had a prolonged follow-up. Most preventive measures of VDT-associated DED aimed to increase blink rate or directly prevent tear film instability, ocular inflammation, mucin loss or ocular surface damage. Using an adjustable chair and ergonomic training, blink animations and omega-3 supplementation improved signs and symptoms of VDT-associated DED. Taking frequent breaks was associated with fewer symptoms, but no study assessed the commonly suggested 20-20-20 rule., Conclusion: Preventive measures, such as blink animation programmes, oral intake of omega-3 fatty acids and improved ergonomics act on different parts of the vicious cycle of dry eye and could supplement each other. A comparison of the efficacy of the different interventions as well as more evidence of the effect of increased humidity, VDT filters and ergonomic practices, are required., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Dry eye disease (DED) is among the most prevalent ophthalmic conditions but is often underdiagnosed and mistreated. Antibiotics are regularly used to treat DED caused by meibomian gland dysfunction (MGD) or blepharitis, but their use has been questioned., Objective: To critically evaluate the use of oral and topical antibiotics in DED management., Methods: A literature search was conducted on November 15th, 2021, in the PubMed database. The search terms were: (antibiotics OR azithromycin OR doxycycline OR minocycline) AND (dry eye disease OR meibomian gland OR blepharitis anterior OR blepharitis posterior OR chronic blepharitis). All relevant original articles with English full-text were included. Case reports and review articles were excluded., Results: The search provided 619 articles, of which 22 met the inclusion criteria. Oral and topical antibiotics appeared to have short-term positive effects on signs and symptoms of blepharitis- or MGD-related DED. However, these improvements often reverted upon cessation of treatment. The need for repeated treatments and mild adverse events were common., Conclusions: Current evidence suggests that patients with blepharitis- or MGD-related DED experience short-term benefits of antibiotics. However, evidence for lasting improvement after completed treatment was lacking. Given the unclear long-term benefits, common side effects, and increasing antibiotic resistance seen globally, the existing literature is not sufficient to conclude that antibiotics are useful in long-term MGD management. A survival-analysis of a single round of antibiotics, in addition to the effects of repeated rounds of treatment, on DED parameters could provide useful insights., Competing Interests: Declaration of competing interest Ragnheiður Ravnaas Vernharðsdóttir declares no conflicts of interest. Morten S. Magno declares no conflicts of interest. Leif Hynnekleiv declares no conflicts of interest. Neil Lagali declares no conflicts of interest. Darlene A. Dartt declares no conflicts of interest. Jelle Vehof declares no conflicts of interest. Catherine J. Jackson declares no conflicts of interest. Tor Paaske Utheim is co-founder and co-owner of The Norwegian dry eye clinic and the Clinic of eye health, Oslo, Norway, which delivers talks for and/or receives financial support from the following: ABIGO, Alcon, Allergan, AMWO, Bausch&Lomb, Bayer, European school for advanced studies in ophthalmology, InnZ Medical, Medilens Nordic, Medistim, Novartis, Santen, Specsavers, Shire Pharmaceuticals and Thea Laboratories. He has served on the global scientific advisory board for Novartis and Alcon as well as the European advisory board for Shire Pharmaceuticals. Utheim is the Norwegian Global Ambassador for Tear Film and Ocular Surface Society (TFOS), a Board Member of the International Ocular Surface Society, an International Member of the Japanese Lid and Meibomian gland working group (LIME), a Consultant at the Norwegian Association for the Blind and Partially Sighted, the President of the Oslo Society of ophthalmology, and the Editor-in-Chief of Oftalmolog, an eye journal distributed to all eye doctors in the Nordic region since 1980. Besides publishing articles of presumed interest to our readers, Oftalmolog publishes advertisements from pharmaceutical companies, companies selling ophthalmological equipment, and associations organizing conferences and events in ophthalmology. For more information, visit: oftalmolog.com., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dry eye disease affects millions of people worldwide, causing pain, vision disturbance, and reduced productivity. Meibomian gland dysfunction, a major cause of dry eye, is characterized by chronic glandular inflammation, thickening of the meibum, obstruction of terminal ducts, and glandular atrophy. Treatment of meibomian gland dysfunction can utilize heat and pressure applied to the meibomian glands, increasing meibum expression. With self-treatments, however, not all patients achieve lasting improvement, and compliance is often low. In-office thermal systems offer a second line of treatment and could be a much-needed addition for patients who do not respond to conventional treatment. We critically evaluated the efficacy and safety of LipiFlow, iLux, and TearCare based on existing literature. While the studies found a single in-office thermal treatment to be safe and effective in improving short-term signs and symptoms in patients with dry eye, long-term efficacy needs to be further evaluated. Thus, well-controlled, long-term efficacy studies are warranted to draw clear conclusions. The treatment seemed to provide rapid relief of symptoms that may last up to 1 year, but at a considerably higher cost than the at-home treatments. The choice of treatment depends on cost, compliance with at-home treatment, and personal preference., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Eyelid warming is an important treatment for meibomian gland dysfunction (MGD). Specialized chambered devices, using warm moist air have been developed., Purpose: To critically evaluate the literature on the safety and efficacy of chambered warm moist air devices in MGD treatment and pinpoint areas of future research., Methods: PubMed and Embase were searched on 06 June 2021. The search term was '(warm OR heat OR steam OR goggle OR spectacle OR moist air) AND (meibomian OR MGD OR blepharitis OR eyelid OR dry eye OR DED)'. All relevant articles with available English full text were included., Results: Eighteen articles assessing the application of chambered warm moist air eyelid warming devices were identified. In single-application studies, steam-based eyelid warming increased the eyelid temperature and improved symptoms, lipid layer thickness, and tear film breakup time (TBUT). In treatment studies, the steam-based devices improved TBUT and symptom scores. However, in the only randomized controlled trial (RCT) comparing chambered steam-based heat to hot towel treatment, there was no difference between groups for the primary outcome measure; the proportion of subjects noting symptom improvement after 4 weeks., Conclusion: Currently available chambered warm moist air eyelid warming devices are safe and effective at raising eyelid temperature to therapeutic levels and improving signs and symptoms of dry eye. However, it is not clear if they provide a greater benefit than other eyelid warming therapies. Further well-conducted RCTs comparing moist and dry heat devices should be conducted on patients across the range of DED severities and subtype spectrum., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Dry eye disease (DED) is a multifactorial disease of the tear film and ocular surface. It causes ocular symptoms, reduced quality of life and a considerable economic burden on society. Prolonged use of visual display terminals (VDTs) has been suggested as an important risk factor for DED., Purpose: This review aims to study the association between DED and VDT use with an emphasis on the prevalence of DED among VDT users and harmful daily duration of VDT use., Methods: A PubMed search was conducted and yielded 57 relevant articles based on a set of inclusion and exclusion criteria. The studies were subclassified according to study design., Results: The far majority of the studies showed an association between VDT use and DED or DED-related signs and symptoms. The prevalence of definite or probable DED in VDT and office workers ranged from 26% to 70%, with as few as 1-2 hr of VDT exposure per day being associated with DED., Conclusion: VDT use is strongly associated with DED. VDT-associated DED is prevalent, but the exact prevalence needs to be further elucidated using standardized DED diagnosis criteria. Furthermore, a safe lower limit of daily VDT use has yet to be established. More research is needed on the effect of digitalization and digital transformation, which are particularly high during the time of the COVID-19 pandemic., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To investigate the relationship between dry eye disease (DED) and vision-related quality of life (VR-QoL) at population level., Methods: DED and VR-QoL were assessed in 89,022 participants (18-96 years, 59% female) from the Dutch population-based Lifelines cohort using the Women's Health study (WHS) and Visual function 25 (VFQ25) questionnaires. The relationship between DED and compromised VR-QoL was assessed with logistic regression, corrected for age, sex, BMI, income, education, smoking, and 55 comorbidities., Results: 9.1% of participants had DED. The participants with DED had higher risk of compromised average of ten domains of VR-QoL (OR 3.12 (95% CI 2.98-3.27) corrected for age, sex, BMI, income, smoking, and 55 comorbidities). Increasing symptom frequency was highly associated with decreasing VR-QoL (P < 0.0005). In all VR-QoL domains, including measures of daily visual function and emotional well-being, DED was clearly associated with compromised VR-QoL. Compared to macular degeneration, glaucoma, retinal detachment, and allergic conjunctivitis, DED presented similar or higher risks for compromised score on all VR-QoL domains. The population-attributable fraction of DED for compromised general vision exceeded that of other eye diseases investigated, especially in the younger age groups., Conclusion: DED is associated with reductions in all domains of VR-QoL, also after correction for associated comorbidities. We found that DED imposes an extensive population burden regarding compromised VR-QoL due to its high prevalence and substantial impact on VR-QoL, higher than that for other common vision-affecting eye disorders. Our results emphasize the importance of recognizing DED as a serious disorder from both patient and public health perspectives., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To date, population-based studies reporting associations between dry eye disease and medications were hypothesis-driven, did not take into account underlying comorbidities, and did not investigate individual drugs. The purpose of this study was to clarify the association of dry eye symptoms with medication classes and individual drugs, using a hypothesis-free approach., Methods: 79,606 participants (age 20-97 years, 59.2% female) from the population-based Lifelines cohort in the Netherlands were cross-sectionally assessed for dry eye symptoms using the Womens' Health Study dry eye questionnaire. All medications used were coded with the ATC classification system. Logistic regression was used to assess the risk of the 59 most-used therapeutic/pharmacological subgroups and the 99 most-used individual drugs (all n > 200) on dry eye symptoms, correcting for age, sex, body mass index, and 48 comorbidities associated with dry eye., Results: Thirty-eight (64%) medication subgroups and fifty-two (53%) individual drugs were associated with dry eye symptoms (P < 0.05), after correction for age and sex only. A multivariable model correcting for comorbidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (particularly proton pump inhibitors (PPIs)), antiglaucoma and anticholinergic medications., Conclusions: This study underlines that medication use is highly informative of risk of dry eye symptoms. Correction for underlying comorbidities is critical to avoid confounding effects. This study confirms suggested associations between medications and dry eye symptoms at a population level and shows several new associations. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed., (Copyright © 2021. Published by Elsevier Inc.)

Background: Recent randomised controlled trials (RCTs) in primary Sjögren's syndrome used the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) as their primary endpoint. Given the heterogeneous and complex nature of primary Sjögren's syndrome, it might be more appropriate to also assess other clinically relevant disease features. We aimed to develop a novel composite endpoint for assessing treatment efficacy in patients with primary Sjögren's syndrome: the Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS)., Methods: A multidisciplinary expert team selected clinically relevant items and candidate measurements for inclusion in the composite score. For each measurement, cutoff points for response to treatment were chosen based on expert opinion, previously published data on minimal clinically important improvements, and trial data, primarily the week-24 data of the single-centre ASAP-III trial of abatacept versus placebo. CRESS was validated using data from three independent RCTs: one trial of rituximab (TRACTISS), one of abatacept (multinational trial), and one of tocilizumab (ETAP). We calculated the number and percentage of patients who were responders in the separate CRESS items, and the percentage of responders based on the total CRESS at the primary endpoint visits (week 48 for TRACTISS, week 24 for the other two trials). Patients with fewer than three items available for evaluating CRESS response were imputed as non-responders., Findings: Based on expert opinion, five complementary items were selected to assess response: (1) systemic disease activity by Clinical ESSDAI (less than 5 points); (2) patient-reported symptoms by EULAR Sjögren's Syndrome Patient Reported Index, assessed by a decrease of at least 1 point or at least 15% from baseline; (3) tear gland item by Schirmer's test and ocular staining score, assessed by an increase of at least 5 mm or decrease of at least 2 points, respectively, in patients with abnormal Schirmer's test or ocular staining score findings at baseline, or, in patients with normal baseline values, assessed by no change to abnormal for both; (4) salivary gland item, assessed by unstimulated whole saliva secretion (increase of at least 25%) and salivary gland ultrasonography (decrease of at least 25%); and (5) serology, assessed by rheumatoid factor (decrease of at least 25%) and IgG (decrease of at least 10%). Total CRESS response is defined as response on at least three of five items. Post-hoc assessment of phase 3 trial data showed that CRESS response rates at the primary endpoint visits were 60% (24 of 40) for abatacept versus 18% (seven of 39) for placebo (p<0·0001) in ASAP-III, 49% (33 of 67) for rituximab versus 30% (20 of 66) for placebo (p=0·026) in the TRACTISS trial, 45% (41 of 92) for abatacept versus 32% (30 of 95) for placebo (p=0·067) in the multinational abatacept trial, and 18% (10 of 55) for tocilizumab versus 24% (13 of 55) for placebo (p=0·48) in the ETAP trial., Interpretation: The CRESS is a feasible, well-balanced, composite endpoint for use in trials of primary Sjögren's syndrome. As a next step, the CRESS will require validation in a prospective RCT., Funding: None., Translation: For the Dutch translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests ANB reports personal fees from Bristol-Myers Squibb and Sanofi-Aventis, outside the submitted work. MB reports grants and personal fees from Amgen/Medimmune, Janssen, and GSK, and personal fees from UCB, outside the submitted work. HB reports grants and personal fees from Bristol Myers Squibb and Roche, and personal fees from Novartis, Medimmune, personal fees and Union Chimique Belge, outside the submitted work. SJB reports consulting fees from Novartis, AstraZeneca, and Abbvie/Galapagos, outside the submitted work. J-EG reports grants and personal fees from Bristol Myers Squibb and Pfizer, and personal fees from CSL Behring, Lilly, Janssen, UCB, and Roche, outside the submitted work. FGMK reports grants and personal fees from Bristol Myers Squibb and Roche, and personal fees from Janssen-Cilag, outside the submitted work. MN and NR are employees and shareholders of Bristol-Myers Squibb. JFvN reports personal fees from Bristol Myers Squibb, outside the submitted work. JV reports personal fees from Santen and Tramedico, outside the submitted work. AV reports grants from Bristol Myers Squibb and Roche, during the conduct of the study. SA, LdW, GMPJV, EP, and RF declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)