Search

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.

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.

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.

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 in-dividual 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 comor-bidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (partic-ularly 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 associa-tions. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed.

Purpose: This large cross-sectional population-based study investigated the relationship between dry eye disease (DED) and health-related quality of life (HR-QoL). Methods: Dry eye and HR-QoL were assessed in 78,165 participants (19-94 yrs, 59.2% female) from the Dutch population-based Lifelines cohort, using the WHS and the SF36 questionnaire, respectively. Logistic regression was used to assess the relationship between DED and below median Physical Component Summary (PCS) and Mental Component Summary (MCS) score, corrected for age, sex, education, BMI, and 52 comorbidities. Results: Overall, 8.9% of participants had DED. Participants with DED had an increased risk of low PCS (OR 1.54 (95% CI 1.46-1.62)) and MCS scores (OR 1.39 (95% CI 1.32-1.46)), corrected for age and sex. This risk remained significant after correction for comorbidities (P < 0.0005). Increasing DED symptom frequency was associated with decreasing HR-QoL (P < 0.0005). Undiagnosed DED subjects had a significantly increased risk of low mental HR-QoL with increasing dry eye symptoms compared to diagnosed subjects (P < 0.0005). Compared to allergic conjunctivitis, glaucoma, macular degeneration and retinal detachment, DED showed the highest risk of low HR-QoL. Compared to other common systemic and chronic disorders, such as depression, rheumatoid arthritis, and COPD, DED was distinctive by having a substantial reduction in both PCS and MCS. Conclusion: DED is associated with substantial reductions in both physical and mental HR-QoL, also after correction for associated comorbidities. Not having a diagnosis is associated with worse mental HR-QoL in subjects with severe DED. Our results underline the importance of recognizing dry eye as a serious disorder.

Purpose To assess the association between dry eye disease (DED) and alcohol consumption using a large population-based cohort. Methods 77,145 participants (19–94 years, 59% female) from the Dutch Lifelines cohort were cross-sectionally assessed for DED using the Women's Health Study (WHS) dry eye questionnaire. Alcohol intake was assessed using self-reported food frequency questionnaires. The relationship between DED and alcohol use was analyzed using logistic regression, corrected for age, sex, BMI, smoking status, education, income, and 55 potentially confounding comorbidities. Results Overall, 30.0% of participants had symptomatic dry eye. Alcohol use significantly increased the risk of symptomatic dry eye in females (odds ratio [OR] 1.095, 95%CI 1.045–1.148), but not in males (OR 0.988, 95%CI 0.900–1.084). Contrarily, in male drinkers, increasing alcohol intake (in 10 g/day) had a protective effect on symptomatic dry eye (OR 0.962, 95%CI 0.934–0.992), which was not seen in females (OR 0.986, 95%CI 0.950–1.023). Alcohol use and intake had a sex-specific effect on all outcomes of DED assessed: symptomatic dry eye, highly symptomatic dry eye, clinical diagnosis, and WHS definition dry eye. Conclusions This large population-based study found alcohol use to have a clear sex-specific effect on DED, presenting as a risk-factor only in females. This adds to the evidence of sex-specific pathophysiological mechanisms of dry eye and illustrates the importance of sex stratification in studies investigating DED. The mild protective effect of increased alcohol intake in male drinkers is advised to be interpreted with caution, as alcohol's other health effects might be of greater clinical significance.

Purpose: To improve upon self-reported glaucoma status in population-based cohorts by developing a questionnaire-based proxy incorporating self-reported status in conjunction with glaucoma-specific visual complaints. Methods: A vision specific questionnaire, including questions from the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) was administered to 79,866 Lifelines participants, a population-based cohort study in the Northern Netherlands. We compared NEI-VFQ-25 responses between ‘definite’ glaucoma cases (n = 90; self-reported surgical cases) and an age- and gender-matched subset of controls (n = 1,800) to uncover glaucoma-specific visual complaints, using a case–control logistic regression. We defined ‘probable glaucoma’ as both self-reported disease status and visual complaints, and ‘possible glaucoma’ as either. To evaluate the resulting proxy, we determined age-stratified glaucoma prevalences in the remaining cohort and compared the result to the literature. Results: Per unit increase in the vision subscales (range 0–100) distance, peripheral and low luminance, we observed significantly increased odds of definite glaucoma (2% [P = 0.03], 4% [P = 1.2 × 10−8] and 2% [P = 0.02], respectively); the associated area under the curve was 0.73. We identified 300 probable and 3,015 (1,434 by self-report) possible glaucoma cases. Standardised prevalences of definite, probable and possible glaucoma for 55+ were 0.4%, 1.1% and 7.3%, respectively. For self-reported glaucoma (combining definite, probable and possible by self-report), this was 5.2%. Conclusions: The combination of self-reported glaucoma status and visual complaints can be used to capture glaucoma cases in population-based settings. The resulting prevalence of combined definite and probable glaucoma (1.5%) appears to be more consistent with previous reports than the prevalence estimate of 5.2% based only on self-report.

ObjectiveTo investigate salivary gland ultrasound (SGUS) abnormalities in relation to clinical phenotype and patient characteristics, disease activity, and disease damage in patients with primary Sjögren syndrome (pSS).MethodsConsecutive outpatients included in our REgistry of Sjögren Syndrome LongiTudinal (RESULT) cohort were selected. Patients with pSS who were included were classified according to the American College of Rheumatology/European League Against Rheumatism (EULAR) criteria and underwent full ultrasonographic examination (Hocevar score 0–48) at baseline. Total SGUS scores of ≥ 15 were considered positive. Patient characteristics, disease activity, and disease damage were compared between the different SGUS groups.ResultsIn total, 172 of 186 patients with pSS were eligible, of whom 136 (79%) were SGUS positive. Compared with patients who were SGUS negative, SGUS-positive patients had significantly longer disease duration, higher EULAR Sjögren Syndrome Disease Activity Index, higher Sjögren Syndrome Disease Damage Index, and were more likely to have a positive parotid gland biopsy, anti-SSA/SSB antibodies, and abnormal unstimulated whole saliva (UWS) and ocular staining score (OSS), and higher levels of IgG and rheumatoid factor. Regarding patient-reported outcome measurements (PROM), patients who were SGUS positive scored significantly lower on the EULAR Sjögren Syndrome Patient-Reported Index for fatigue and pain, and more often found their disease state acceptable compared with patients who were SGUS negative. SGUS total score showed significant associations with various clinical and serological variables, and with PROM. Highest associations were found for UWS (ρ = –0.551) and OSS (ρ = 0.532).ConclusionPatients who were SGUS positive show a distinct clinical phenotype in all aspects of the disease compared with patients who were SGUS negative: clinical, functional, serological, and PROM. SGUS could be a helpful tool in selecting patients for clinical trials and estimating treatment need.

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. publishedVersion

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.

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. This research was partly funded by NFR 271555 grant by the Norwegian Research Council, through the Medical Student Research Program. D.A. Dartt was supported by grants from the US NIH: R01 EY019470, R01 EY029789 and R01 EY021292.

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. publishedVersion

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. This research was partly funded by NFR 271555 grant by the Norwegian Research Council, through the Medical Student Research Program. D.A. Dartt: NIH R01 EY019470, NIH R01 EY029789.

Introduction: Environmental factors play an important aetiological role in dry eye.This cross-sectional study investigated the relationship between types of occupation and symptomatic dry eye.Methods: 40,501 employed people working >= 8 h a week were included from the population-based Lifelines cohort in the Netherlands. Logistic regression was used to determine the association between symptomatic dry eye (assessed by the WHS questionnaire) and occupation (using the ISCO-08 classification system).Results: After correction for age and sex, the professionals (e.g. legal, health, and business and administration professionals) (OR = 1.14, 95%CI = 1.08-1.19, P Conclusions: This study underlines the importance of asking about type of occupation in dry eye patients. Screening for symptomatic dry eye in high risk occupations such as in building workers and in indoor occupations with high screen use is relevant from an occupational health and work productivity perspective. The lower risk of dry eye in outdoor and active occupation is intriguing and justifies future studies to investigate potential protective and treatment effects.

Purpose: Sleep is an important determinant of health and quality of life. This study aimed to clarify the association between dry eye and sleep quality using a large population-based cohort.Methods: 71,761 participants (19-94 yrs, 59.4% female) from the Lifelines cohort in the Netherlands were assessed for dry eye using the Women's Health Study Dry Eye Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to examine the relationship between poor sleep quality (PSQI score > 5) and dry eye, while correcting for age, sex, BMI, education, income, and 51 possible confounding comorbidities, including autoimmune diseases and psychiatric disorders.Results: Overall, 8.9% of participants had dry eye. Of these, 36.4% had poor sleep quality compared to 24.8% of controls (OR 1.52 (95%CI 1.44-1.60), P < 0.0001, corrected for age and sex). After correcting for all comorbidities, dry eye was still associated with poor sleep (OR 1.20 (95%CI 1.11-1.28), P < 0.0001). This relationship was seen across all ages and sexes. Patients with dry eye scored worse on all subcomponents of the PSQI. Almost one-in-two (44.9%) persons with dry eye symptoms "often" or "constantly" had poor sleep quality. This proportion was similar to participants with sleep apnea and osteoarthritis. Additionally, increasing symptom frequency was tied to increased prevalence of poor sleep quality.Conclusions: All components of sleep quality were significantly reduced in participants with dry eye, even after correcting for comorbidities. These results indicate the substantial impact of dry eye on patients' lives, especially for those with frequent symptoms.

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. This research has been finded by the Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway (TPU) and the US National Institutes of Health Grants R01 EY029789 (DAD) and EY019470 (DAD).

The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.

PURPOSE. Refractive errors, particularly myopia, are common and a leading cause of blind-ness. This study aimed to explore associations between medications and refractive error in an aging adult cohort and to determine whether childhood-onset refractive errors predict future medication use to provide novel insights into disease mechanisms.METHODS. The study compared the spherical equivalent values measured in 102,318 UK Biobank participants taking the 960 most commonly used medications. The strengths of associations were evaluated against the self-reported age of spectacle wear. The causality of refractive error changes was inferred using sensitivity and Mendelian randomization analyses.RESULTS. Anti-glaucoma drugs were associated with 1 to 2 diopters greater myopic refrac-tion, particularly in subjects who started wearing correction in the first two decades of life, potentially due to the association of higher intraocular pressure since early years with both myopia and, later in life, glaucoma. All classes of pain-control medications, including paracetamol, opiates, non-steroidal antiinflammatory drugs, and gabapentinoids, were associated with greater hyperopia (+0.68-1.15 diopters), after correction for deprivation, education, and polypharmacy and sensitivity analyses for common diagnoses. Oral hypoglycemics (metformin, gliburonide) were associated with myopia, as was allopurinol, and participants using bronchodilators (ipratropium and salbutamol) were more hyperopic.CONCLUSIONS. This study finds for the first time, to our knowledge, that medication use is associated with refractive error in adults. The novel finding that analgesics are associated with hyperopic refraction, and the possibility that multisite chronic pain predisposes to hyperopia, deserves further research. Some drugs, such as antihyperglycemic or bronchodilators, may directly alter refractive error. Intraocular pressure appears causative for myopia.

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. publishedVersion

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.

Purpose: To investigate the prevalence of dry eye among all adult age categories and to discover independent risk factors by investigating a wide range of etiological categories.Methods: A cross-sectional association study including 79,866 voluntary participants aged 20-94 years of the population-based Lifelines Cohort Study in the Netherlands.Results: Overall, 9.1% of participants had dry eye disease as measured by the Women's Health Study dry eye questionnaire. Prevalence of dry eye symptoms were particularly prevalent in 20-30 years olds. Dry eye was associated with comorbidities in almost all body systems, including musculoskeletal, gastro-intestinal, ophthalmic, autoimmune, psychiatric, pain, functional, dermatological and atopic disorders. Numerous independent risk factors were discovered or confirmed, with strong associations for female sex, contact lens use, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, eye surgery including cataract and laser refractive surgery, keratoconus, osteoarthritis, connective tissue diseases, atherosclerosis, Graves' disease, autistic disorder, depression, 'burnout', Crohn's disease, sarcoid, lichen planus, rosacea, liver cirrhosis, sleep apnea, sinusitis, thyroid function, and air pollution (NO2). High blood pressure and high BMI were strongly associated with less dry eye, as was current smoking, while ex-smokers had more dry eye. No clear link between dry eye and lipid or blood glucose levels was found.Conclusions: This study on dry eye confirmed but also refuted many risk factors from smaller epidemiological studies, and discovered numerous new risk factors in multiple etiological categories. The finding that dry eye symptoms are particularly common in young adults is concerning, and warrants further study.

The subcommittee reviewed the prevalence, incidence, risk factors, natural history, morbidity and questionnaires reported in epidemiological studies of dry eye disease (DED). A meta-analysis of published prevalence data estimated the impact of age and sex. Global mapping of prevalence was undertaken. The prevalence of DED ranged from 5 to 50%. The prevalence of signs was higher and more variable than symptoms. There were limited prevalence studies in youth and in populations south of the equator. The meta-analysis confirmed that prevalence increases with age, however signs showed a greater increase per decade than symptoms. Women have a higher prevalence of DED than men, although differences become significant only with age. Risk factors were categorized as modifiable/non-modifiable, and as consistent, probable or inconclusive. Asian ethnicity was a mostly consistent risk factor. The economic burden and impact of DED on vision, quality of life, work productivity, psychological and physical impact of pain, are considerable, particularly costs due to reduced work productivity. Questionnaires used to evaluate DED vary in their utility. Future research should establish the prevalence of disease of varying severity, the incidence in different populations and potential risk factors such as youth and digital device usage. Geospatial mapping might elucidate the impact of climate, environment and socioeconomic factors. Given the limited study of the natural history of treated and untreated DED, this remains an important area for future research.

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 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.

PURPOSE: To investigate the role of sex on the symptomatology of DED and on the associations between symptoms and signs.METHODS: A cross-sectional study was used including 755 dry eye patients from the Groningen Longitudinal Sicca Study (GLOSSY cohort). Patient symptoms were assessed by the Ocular Surface Disease Index (OSDI) questionnaire and dry eye signs by the six most commonly used tests. Patients were divided in groups based on overall severity of signs and within these groups total and specific symptoms were compared by sex. Sex differences in Spearman correlation between symptoms and signs were calculated.RESULTS: Women had higher total symptom scores than men in both the mild (33.8 vs 24.7, P = .01) and moderate signs groups (38.3 vs 28.0, P CONCLUSIONS: This large clinical study has shown that sex has a large influence on the symptomatology of DED, with significantly higher symptom scores and lower correlation between symptoms and signs in women compared to men. These findings are of importance in clinical practice and in conducting research into DED.

Recent studies have provided consistent evidence for a genetic influence on chronic widespread pain (CWP). The aim of this study was to investigate (1) the etiological structure underlying CWP by examining the covariation between CWP and psychological comorbidities and psychoaffective correlates and (2) the decomposition of the covariation into genetic and environmental components. A total of 3266 female twins (mean age 56.6 years) were subject to multivariate analyses. Using validated questionnaires to classify twins as having CWP, the prevalence of CWP was 20.8%. In the multivariate analysis, the most suitable model was the common pathway model. This model revealed 2 underlying latent variables, one common to anxiety, emotional intelligence, and emotional instability (f1) and the other common to depression and CWP (f2), the latter being highly heritable (86%). Both latent variables (f1 and f2) shared an additive genetic and a nonshared environmental factor. In addition, a second additive genetic factor loading only on f2 was found. This study reveals the structure of genetic and environmental influences of CWP and its psychoaffective correlates. The results show that the clustering of CWP and depression is due to a common, highly heritable, underlying latent trait. In addition, we found evidence that CWP, anxiety, emotional instability, and emotional intelligence are influenced by different underlying latent traits sharing the same genetic and nonshared environmental factors. This is the first study to reveal the structure and relative importance of genetic and environmental influences on complex etiological mechanisms of CWP and its correlates.

To estimate the prevalence and risk factors of dry eye disease (DED) in a female cohort in the UK.Population-based cross-sectional association study of 3824 women from the TwinsUK cohort aged 20-87 years. A questionnaire was used to evaluate DED and several risk factors. Binary logistic regression, corrected for age, was used to examine the association between DED and risk factors.9.6% of women had a DED diagnosis and concomitant use of artificial tears, and 20.8% experienced DED symptoms in the past 3 months. Risk factors that were significantly associated with DED were age, asthma, eczema, the presence of any allergy, cataract surgery, rheumatoid arthritis, osteoarthritis, migraine and stroke. The highest effect sizes were found with depression, pelvic pain, irritable bowel syndrome and chronic widespread pain syndrome (all p0.0005). Subjects with DED symptoms scored significantly lower on self-perceived health, compared with controls (p=0.001).DED is common and increases with age within this cohort of female twins. We confirmed established risk factors for the first time in a British population, and found important risk factors that might relate to an underlying aetiology involving chronic pain predisposition or somatisation.

Chronic pain syndromes (CPS) are highly prevalent in the general population, and increasingly the evidence points to a common etiological pathway. Using a large cohort of twins (n = 8564) characterized for chronic widespread musculoskeletal pain (CWP), chronic pelvic pain (PP), migraine (MIG), dry eye disease, and irritable bowel syndrome (IBS), we explored the underlying genetic and environmental factors contributing to CPS and the correlation between them. The sample was predominantly female (87.3%), with a mean age of 54.7 (+/- 14.7) years. Prevalence of the different CPS ranged from 7.4%.(PP) to 15.7% (MIG). For all CPS the within-twin correlation in monozygotic twin pairs was higher than in dizygotic pairs, suggesting a heritable component. Estimated heritability ranged from 19% (IBS) to 46% (PP). Except fOr MIG, we found significant pairwise phenotypic correlations between the CPS. The phenotypic correlation was highest between CWP and IBS (0.40; 95% confidence interval: 0.27 to 0.46). Excluding MIG from further analyses, cross-twin cross-trait correlations were higher in monozygotic compared with dizygotic twin pairs, suggestive of shared genetic factors between CWP, PP, IBS, and dry eye disease. Twin modeling analysis revealed the common pathway model as the model best explaining the observed pattern of correlation between the traits, with an estimated heritability of 66% of the underlying latent variable. These results are evidence of shared genetic factors in conditions manifesting chronic pain and justify the search for underlying genetic variants. (C) 2014 International Association for the Study of Pain. Published by Elsevier By. All rights reserved.

Department of Twin Research & Genetic Epidemiology, King’s College London, St Thomas’ Hospital, London, UK Department of Ophthalmology & Epidemiology, University Medical Center Groningen, Groningen, The Netherlands *Author for correspondence: frances.williams@kcl.ac.uk

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.

Rationale Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. Objectives We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). Methods We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. Results A significant association of interaction between haplotype rs346074–rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. Conclusions This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics. Electronic supplementary material The online version of this article (doi:10.1007/s00213-011-2211-x) contains supplementary material, which is available to authorized users.

Background Weight gain is one of the major problems in patients using antipsychotic medication, leading to relevant morbidities and reduced compliance to pharmacotherapy. Recently, an association has been reported between a single nucleotide polymorphism (rs1455832) of the roundabout axon guidance receptor, homolog 1 (ROBO1) gene and body mass index (BMI) in persons younger than 30 years. The aim of this study is to investigate the association between BMI and rs1455832 in patients with a psychotic disorder using antipsychotics.Methods A cross-sectional design was used in a pooled sample of Caucasian psychiatric patients obtained from three comparable Dutch psychiatric populations. Patients were eligible for inclusion in this study if they met the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a nonaffective psychotic disorder, were 18 years or older, and used one or more antipsychotics. Genotyping was performed according to standard protocols. Linear (for BMI) and logistic (for obesity, defined as BMI>30) regression analyses, corrected for age and sex, were applied in the statistical analyses.Results A total of 435 patients were included in this association analyses. The rs1455832 polymorphism studied was significantly associated with BMI and obesity in female patients. Female patients had a statistically significant (P=0.025) decrease of 1.76 kg/m(2) in BMI values per C allele. In contrast to female patients, this association was not exhibited in male patients.Conclusion The rs1455832 polymorphism may play a role in inducing obesity in female patients using antipsychotics. Psychiatr Genet 21:202-207 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

The prevalence of the metabolic syndrome is increased in patients with schizophrenia compared with the general population. The strong interindividual differences in susceptibility to developing the metabolic syndrome suggests that the genetic makeup is a modulating factor. Part of the genetic puzzle can possibly be explained by variations in the gene coding for the adrenergic alpha-2a receptor (ADRA2A) because this receptor plays an important role in lipolysis.Three studies have found an association between the alpha-2a 1291-C/G polymorphism and antipsychotic induced weight gain, with conflicting results between whites and Asians. No studies have been published investigating the association between the 1291-C/G polymorphism and the metabolic syndrome.The primary objective of this cross-sectional study was to investigate the association between the ADRA2A 1291-C/G polymorphism and the metabolic syndrome in 470 patients using antipsychotic drugs.There was no significant association between carriership of the variant 1291-G allele and prevalence of the metabolic syndrome (odds ratio, 0.73; 95% confidence interval, 0.49Y1.15). Exploratory analysis showed an association between carriership of the variant 1291-G allele and a reduced prevalence of the metabolic syndrome in patients not currently using antipsychotics (odds ratio, 0.05; 95% confidence interval, 0.003Y0.97; P = 0.048).In conclusion, this study shows that the ADRA2A 1291-C/G polymorphism does not seem to be a strong predictor for long-term occurrence of the metabolic syndrome in antipsychotic using patients. Studies investigating this association using a prospective, or retrospective, design, as well as studies investigating this association in a nonpsychiatric population, are warranted.

Objective: The study's objective was to analyze the adoption and persistence of risperidone long-acting injectable (RLAI) therapy after its introduction in the Netherlands in 2003 compared with the adoption and persistence of existing first-generation antipsychotic (FGA) depot drugs as an example of the diffusion of a new drug in the Netherlands.Methods: Data on antipsychotic use were obtained from the InterAction DataBase (IADB.nl), a database containing pharmacy dispensing records of patients in the northern Netherlands, from May 20, 2003, to December 31, 2006. Treatment complexity for patients prescribed RLAI was analyzed on the basis of psychotropic comedication at baseline and during treatment, as well as on the number of previous antipsychotic therapies. Differences in treatment complexity between patients using RLAI and those using FGA depot drugs were estimated using parametric regressions. To evaluate persistence, survival analysis techniques were applied to estimate the probability of patients continuing the use of RLAI or FGA depot drugs over tu-ne.Results: Data on 435 patients who were treated with depot antipsychotics were extracted from the IADB.nl. Patients had a mean (SD) age of 40.7 (13.8)),ears, and 65% of them were male. The results of this analysis indicated that persistence for patients prescribed RLAI was significantly lower compared with other depot antipsychotics (RLAI VS zuclopenthixol, P = 0.002; RLAI vs all other depot antipsychotics, P = 0.009). At the initiation of treatment, patients prescribed RLAI had more previous psychotropic comedication and had, on average, similar to 5 and similar to 1.5 times more prior depot drug therapies compared with zuclopenthixol and any other FGA depot drug, respectively.Conclusions: The findings of this study Suggest that RLAI has been prescribed more often for difficult-to-treat patients than have other available depot antipsychotics. This may explain the low adoption and poor persistence observed in the first few years after the introduction of RLAI. Further research with more extensive data Should be pursued to obtain better understanding of the current diffusion of RLAI in daily clinical practice. (Clin Tber. 20-10;32:108-118) (C) 2010 Excerpta Medica Inc.

Background: Risperidone long-acting injectable (RLAI), the first second-generation depot antipsychotic, has extensively been studied before introduction. Thereafter, questions about the type of patients actually treated with RLAI in daily practice remain to be answered for making valid antipsychotic treatment comparisons involving RLAI in observational studies.Objective: We aimed to determine in chronic antipsychotic users who switched treatment, predictors for the prescription of (1) depot versus oral antipsychotics and (2) RLAI versus first-generation antipsychotics (FGAs) depot.Methods: We used pharmacy dispensing data from 53 community pharmacies in the northeast of the Netherlands containing approximately 500,000 persons. Chronic antipsychotic users were defined and followed up for a switch in antipsychotic treatment within the first period that RLAI was on the market. Multivariable analysis was performed to relate patient, prescriber, and medication characteristics to prescription of a new antipsychotic drug.Results: Predictors for switching to depot versus oral antipsychotics were male sex, previous use of depot antipsychotics, recent anticholinergic drug use, and a gap in antipsychotic dispensation history. Predictors for switching to RLAI versus FGA depot were previous use of depot and consulting a specialist.Conclusions: The results suggest that, compared with oral antipsychotics, patients receiving a depot are less compliant users, with more extrapyramidal side effects. Compared with FGA depot, patients receiving RLAI tend to be more severely ill patients. We conclude that RLAI may be partly channeled to patients as a last resort, which may have important consequences for the interpretation of observational effectiveness comparisons between RLAI and other antipsychotics in daily practice.

PurposeTo evaluate postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment (RRD) and its association with visual function, vision related quality of life, and optical coherence tomography (OCT) findings.Methods45 patients with primary macula-off RRD were included. At 12 months postoperatively, data on metamorphopsia using sine amsler charts (SAC), best corrected visual acuity (BCVA), letter contrast sensitivity, color vision (saturated and desaturated color confusion indexes), critical print size, reading acuity, the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and OCT, were obtained.ResultsMetamorphopsia was present in 39 patients (88.6%), with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score = 1). Patients with metamorphopsia had significantly worse postoperative BCVA (p = 0.02), critical print size (pConclusionThe prevalence of postoperative metamorphopsia in macula-off RRD patients is high, however, the degree of metamorphopsia is relatively low. When metamorphopsia is present, visual functions seem to be compromised, while vision related quality of life is only mildly affected.

PURPOSE. We estimated the relative importance of genes and environment in dry eye disease (DED) using a classic twin study.METHODS. A large sample of 3930 female monozygotic and dizygotic twins from the UK Adult Twin Registry (TwinsUK) was questioned about the presence of a DED diagnosis and about DED symptoms in the preceding 3 months. In addition, a subset of 606 twins was examined for several dry eye signs. Genetic and environmental effects were estimated using maximum likelihood structural equation modeling.RESULTS. All DED outcome variables showed higher correlation in monozygotic twin pairs than in dizygotic twin pairs, suggesting genes have a contributory role in DED. The DED symptoms showed a heritability of 29% (95% confidence interval [CI], 18%-40%). A clinician's diagnosis of DED with concurrent use of artificial tears showed a heritability of 41% (95% CI, 26%-56%). Estimates of the heritability of DED signs were 25% (95% CI, 7%-42%) for interblink interval, 58% (95% CI, 43%-70%) for Schirmer value, 40% (95% CI, 25%-53%) for tear osmolarity, and 78% (95% CI, 59%-90%) for the presence of blepharitis. The unique environment explained the remainder of the variance. We found no significant heritability for tear breakup time.CONCLUSIONS. Genetic factors contribute moderately to the diagnosis, symptoms, and the signs of DED. Compared to other ocular phenotypes, the lower heritability might reflect some of the difficulties in objective phenotyping of DED in a population-based sample. However, future genetic studies are now justified and may help in unraveling the pathophysiology of DED.

PURPOSE: To investigate clinical characteristics of dry eye disease (DED) patients with a chronic pain syndrome.DESIGN: Cross-sectional. study.METHODS: Four hundred twenty-five patients of a tertiary care DED patient cohort in the Netherlands were included. Chronic pain syndromes irritable bowel syndrome, chronic pelvic pain, and fibromyalgia were assessed by questionnaires. Outcome variables were the Ocular Surface Disease Index (OSDI) symptom questionnaire, tear osmolarity, Schirmer test, tear breakup time, conjunctival hyperemia, staining of the cornea and conjunctiva, and amount of mucus. Outcomes were cross-sectionally compared between DED patients with a chronic pain syndrome and those without.RESULTS: A total of 74 out of 425 DED patients (17%) had at least 1 chronic pain syndrome. The total symptom score was significantly higher in DED patients with a chronic pain syndrome than in those without (45.8 vs 33.8, P CONCLUSION: In DED patients, chronic pain syndromes are common and are associated with increased severity of DED symptoms across all domains of the OSDI, even though objective ocular surface signs are no worse. In clinical practice, more awareness of chronic pain syndromes might help in understanding the discrepancy between signs and symptoms in DED. (C) 2016 by Elsevier Inc. All rights reserved.

Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic treatment response. 329 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 9 SNPs in 6 candidate genes (DRD2: Taql_A, -141C; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser; COMT: Val158Met; MTHFR: 677-C/T) using standard protocols. Polymorphisms were based on previous studies showing associations with positive symptoms treatment response. The Clinical Global Impression Improvement (CGI-I) scale was used to assess improvement in positive psychotic symptoms since the start of current antipsychotic treatment. Ordinal regression was used for association analyses. Ninety percent of the patients used second generation antipsychotics, with olanzapine (28%) and risperidone (29%) being the most prescribed drugs. Ser9Gly of the dopamine D3 receptor gene (P value 0.034) and 677-C/T of MTHFR (P value 0.019) were tested statistically significant. Gly-carriers and T-carriers, respectively, showed more clinical improvement on the CGI-I. The other polymorphisms did not show a statistically significant association (P values>0.10). In conclusion, we replicated two out of nine of the previously reported associations between polymorphisms and treatment response. The direction and magnitude of the associations presented here in DRD3 (Ser9Gly) and MTHFR (677-C/T) are in line with previous association studies in Caucasian patients. These polymorphisms may be of value for predicting clinical response. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.

Background: In two previous studies we investigated the association between the rs1414334 C/G and 759 C/T polymorphisms in the HTR2C gene, coding for the 5HT2c-receptor, and prevalence of the metabolic syndrome in a schizophrenic population. In both studies we found an association between the variant rs1414334 C-allele and an increased prevalence of the metabolic syndrome. Objectives: The objective of the current study was to try to replicate our previous findings in a different patient sample. Methods: Patients were included from an ongoing ' Pharmacotherapy Monitoring and Outcome survey'. A crosssectional design was used to investigate the association between HTR2C variants and the metabolic syndrome in patients diagnosed with schizophrenia or related disorders. Patients ≥18 years, using antipsychotics, were eligible for inclusion. Primary endpoint was prevalence of the metabolic syndrome. Primary determinants were the 759 C/Tand rs1414334:C>G polymorphisms in the X-linked HTR2c gene. The association between carriership of the variant HTR2C alleles and prevalence of the metabolic syndrome was investigated with logistic regression. Data were investigated for potential confounding effects of age, ethnicity, diagnosis, sex, SSRI's and antipsychotics. Results: 186 patients, mainly male (68%) and Caucasian (93%) were included. Age, sex, antipsychotic drugs, use of SSRI's and DSM-IV diagnosis were confounders and included in the multi-variate analysis. The variant rs1414334 C-allele, but not the variant 759-T allele, was significantly associated with the metabolic syndrome (Adjusted OR 3.99; 95%CI 1.40-11.33). Conclusions: This study confirms our previous findings that the variant rs1414334 C-allele is associated with the metabolic syndrome.

Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system.This study aimed to replicate previously reported associations in candidate genes for acute and tardive antipsychotic-induced MD in a young Caucasian sample.In 402 patients (median age 26 years), a total of 13 polymorphisms were genotyped in eight dopamine-related candidate genes selected a priori from the literature (regarding dopamine and serotonin receptors, dopamine degradation, and free radicals scavenging enzymes pathways).Patients with MD used on average a higher haloperidol dose equivalent when compared to those without MD. The prevalence of MD was high and did not differ between first- and second-generation antipsychotics. Significant associations were found between (a) the TaqI_D polymorphism and akathisia (OR = 2.3, p = 0.001 for each extra C-allele) and (b) the -141C polymorphism and tardive dyskinesia (OR = 0.20, p = 0.001 for each extra Del allele). The other polymorphisms were not significantly associated with an MD.Two associations were found between genetic variation TaqI_D and the -141C polymorphisms in the DRD2 gene and antipsychotic-induced MD; one with acute akathisia and one with tardive dyskinesia. These were previously reported to be associated with tardive dyskinesia and acute parkinsonism, respectively. These results suggest that the contribution of these DRD2 gene variants in the vulnerability of antipsychotic-induced MD takes place in a more general or pleiotropic way.

IMPORTANCE Dry eye disease (DED) is common, but little is known about factors contributing to symptoms of dry eye, given the poor correlation between these symptoms and objective signs at the ocular surface.OBJECTIVE To explore whether pain sensitivity plays a role in patients' experience of DED symptoms.DESIGN, SETTING, AND PARTICIPANTS A population-based cross-sectional study of 1635 female twin volunteers, aged 20 to 83 years, from the TwinsUK adult registry.MAIN OUTCOMES AND MEASURES Dry eye disease was diagnosed if participants had at least 1 of the following: (1) a diagnosis of DED by a clinician, (2) the prescription of artificial tears, and/or (3) symptoms of dry eyes for at least 3 months. A subset of 689 women completed the Ocular Surface Disease Index (OSDI) questionnaire. Quantitative sensory testing using heat stimulus on the forearm was used to assess pain sensitivity (heat pain threshold [HPT]) and pain tolerance (heat pain suprathreshold [HPST]).RESULTS Of the 1622 participants included, 438 (27.0%) were categorized as having DED. Women with DED showed a significantly lower HPT (P=.03) and HPST (P=.003)-and hence had higher pain sensitivity-than those without DED. A strong significant association between the presence of pain symptoms on the OSDI and the HPT and HPST was found (P=.008 for the HPT and P=.003 for the HPST). In addition, participants with an HPT below the median had DED pain symptoms almost twice as often as those with an HPT above the median (31.2% vs 20.5%; odds ratio, 1.76; 95% CI, 1.15-2.71; P=.01).CONCLUSIONS AND RELEVANCE High pain sensitivity and low pain tolerance are associated with symptoms of DED, adding to previous associations of the severity of tear insufficiency, cell damage, and psychological factors. Management of DED symptoms is complex, and physicians need to consider the holistic picture, rather than simply treating ocular signs.