Advances, limitations and future perspectives in the diagnosis and management of dry eye in Sjögren's syndrome.

Primary Sjögren's syndrome is a complex systemic autoimmune disorder that primarily affects exocrine glands such as the lacrimal glands. Dry eye disease is one of the most prevalent complications of Sjögren's syndrome, affecting most patients. It significantly impairs quality of life and management is often difficult and unsatisfactory, in part due to weak correlation between symptoms and signs and poor recognition of the three main subtypes aqueous-deficient, evaporative and neuropathic dry eye. This review provides an overview of key aspects of dry eye disease, such as its multifactorial aetiology and recent insights into pathophysiology. The uses and pitfalls of commonly-used diagnostic tests for dry eye are reviewed, as well as the increasing number of new imaging technologies and biomarkers to refine diagnosis. There are many current and emerging treatment options for dry eye in Sjögren's syndrome, but high-level evidence of efficacy is mostly lacking, as are evidence-based treatment algorithms. All these aspects make the management of dry eye in Sjögren's syndrome challenging.

A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers.

PURPOSE: To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach. DESIGN: Cross-sectional association study. PARTICIPANTS: A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years). METHODS: We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing. MAIN OUTCOME MEASURES: Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED. RESULTS: Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5 androgens, epiandrosterone sulfate (P = 0.0076) was most associated with 2-year incidence of clinician-diagnosed DED. In addition, we found decreased glycerophosphocholines to be associated with DED, although not at metabolome-wide significance. CONCLUSIONS: This hypothesis-free metabolomic approach found decreased serum androgens to be highly associated with DED and adds important evidence to the growing body of research that links androgens to ocular surface disease and DED.

Predictors of Discordance between Symptoms and Signs in Dry Eye Disease.

PURPOSE: To investigate predictors of discordance between symptoms and signs in dry eye disease (DED). DESIGN: Cross-sectional association study. PARTICIPANTS: A total of 648 patients with dry eye from the Groningen LOngitudinal Sicca StudY (GLOSSY), a tertiary dry eye clinic patient cohort from the Netherlands. METHODS: Patient symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Dry eye signs were assessed by tear osmolarity, Schirmer test, tear breakup time, corneal and conjunctival staining, and meibomian gland dysfunction, all in both eyes, and a composite dry eye signs severity score was calculated from these 6 tests for each patient. Linear regression analysis was used to test the association of discordance between symptoms and signs with a wide range of independent variables (demographic and environmental variables, systemic diseases, ocular traits, and medications). MAIN OUTCOME MEASURES: Predictors of discordance between symptoms and signs in DED, defined by the difference between the rank score of the OSDI and the rank score of the dry eye signs severity score. RESULTS: Of the 648 subjects in this cohort, 536 (82.7%) were female and the mean age was 55.8 years (standard deviation, 15.6 years). Significant predictors of greater symptoms than signs were the presence of a chronic pain syndrome, atopic diseases, a known allergy, the use of antihistamines (all P < 0.001), depression (P = 0.003), osteoarthritis (P = 0.008), and the use of antidepressants (P = 0.02). Predictors of lesser symptoms than signs were increased age (P < 0.001) and the presence of Sjögren's disease (P < 0.001) (primary Sjögren's disease, P < 0.001) more than secondary Sjögren's disease (P = 0.08), and graft-versus-host disease (P = 0.04). Furthermore, greater symptoms compared with signs were highly associated with lower self-perceived health (P < 0.001). CONCLUSIONS: This large clinical study has shown that discordance between symptoms and signs in DED is an indicator of self-perceived health. The study found important predictors of greater symptoms to signs but also predictors of lesser symptoms to signs. Awareness of these predictors is helpful in assessing patients with dry eye in clinical practice.

FACTORS ASSOCIATED WITH PENTOSIDINE ACCUMULATION IN THE HUMAN VITREOUS.

PURPOSE: To explore factors associated with pentosidine accumulation in the human vitreous. METHODS: Vitreous samples were obtained during trans pars plana vitrectomy for macular hole or rhegmatogenous retinal detachment. Patient characteristics included age, gender, and diabetes mellitus. Ocular characteristics included pseudophakia, posterior vitreous detachment, and presence of intraocular fibrosis (epiretinal membrane, proliferative vitreoretinopathy, or both). Pentosidine concentration as a measure of accumulation of advanced glycation end products was determined by high performance liquid chromatography. RESULTS: Pentosidine concentrations were measured in 222 vitrectomy samples (118 female and 104 male patients [median age 66 years], treated for macular hole [n = 105] or rhegmatogenous retinal detachment [n = 117]). Pentosidine was found to accumulate significantly with age (P < 0.001). After correction for age, a multivariable linear regression model revealed significantly higher pentosidine values in eyes with intraocular fibrosis (P = 0.001), in phakic as compared with pseudophakic eyes (P = 0.02), and in the absence of a complete posterior vitreous detachment (P = 0.018). The authors found no association with diabetes mellitus or gender. CONCLUSION: This study confirmed an age-related pentosidine accumulation in the vitreous and found new factors relating to pentosidine levels. Findings support the hypothesis of enzyme-induced vitreous liquefaction and the hypothesis of pentosidine as a pro-fibrotic factor.

A comparison between hyaluronic acid and other single ingredient eye drops for dry eye, a review.

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.

Topical glaucoma medications - Possible implications on the meibomian glands.

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.

The work-related burden of dry eye.

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.

Development and validation of a questionnaire-based myopia proxy in adults: the LifeLines Cohort Study.

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.

The relationship between habitual water intake and dry eye disease.

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.

The relationship between sedentary behavior and dry eye disease.

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.

Intense pulsed light treatment in meibomian gland dysfunction: Past, present, and future.

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.

The Relationship Between Caffeine Intake and Dry Eye Disease.

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.

Greater adherence to a mediterranean diet is associated with lower C-reactive protein (CRP) levels, but not to lower odds of having dry eye disease.

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.

Pre-analytical sample handling effects on tear fluid protein levels.

Tear fluid is emerging as a source of non-invasive biomarkers, both for ocular and systemic conditions. Accurate quantification of tear proteins can be improved by standardizing methods to collect and process tear fluid. The aim of this study was to determine sample handling factors that may influence the tear protein biomarker profile. Tear fluid was collected using Schirmer's strips. Tear proteins were extracted by elution through centrifugation. Total protein content was determined using the bicinchoninic acid assay. Key concepts that apply to the entire sample processing cycle are tear sampling, tear storage, protein extraction and data normalization. Differences in wetting or migration length were observed between Schirmer's strips from different manufacturers, and between protein-free and protein-rich solutions. One unit of migration length (mm) did not correspond to one unit of volume (µL). A positive correlation (r = 0.6671, p < 0.0001) was observed between migration length and total tear protein content. The most beneficial storage conditions were strips that were not stored (+ 21.8%), or underwent 'wet' storage (+ 11.1%). Protein recovery was the highest in 400 µL extraction buffer and independent of protein molecular weight. This study helps to explain inter- and intra-variability that is often seen with tear biomarker research. This information is critical to ensure accuracy of test results, as tear biomarkers will be used for patient management and in clinical trials in the near future. This study also highlights the need for standardization of Schirmer's strip manufacturing, tear fluid processing and analyte concentration normalization.

Hot towels: The bedrock of Meibomian gland dysfunction treatment - A review.

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.

Tear and Saliva Metabolomics in Evaporative Dry Eye Disease in Females.

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.

TFOS Lifestyle: Impact of nutrition on the ocular surface.

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.

Topical glaucoma medications - Clinical implications for the ocular surface.

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.

The association between visual display terminal use and dry eye: a review.

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.

The vision-related burden of dry eye.

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.