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

Primary Sjogren'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 Sjogren'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 Sjogren'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 Sjogren's syndrome challenging

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

Primary Sjogren'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 Sjogren'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 Sjogren'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 Sjogren's syndrome challenging

Prevalence and risk factors of dry eye in 79,866 participants of the population-based Lifelines cohort study in the Netherlands

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 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.</p

The relationship between dry eye and sleep quality

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

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.</p

Evidence That Pupil Size and Reactivity Are Determined More by Your Parents Than by Your Environment

Purpose: A classic twin study to evaluate the relative contributions of genetic and environmental factors to resting pupil size and reactivity. Methods: Pupillometry was performed on 326 female twins (mean age 64 years) from the TwinsUK Adult Twin Registry, assessing resting pupil diameter in darkness and increasing levels of ambient light, alongside dynamic pupillary characteristics. Maximum-likelihood structural equation models estimated the proportion of trait variance attributable to genetic factors. Results: Mean (SD) pupil diameter in darkness was 5.29 mm (0.81), decreasing to 3.24 mm (0.57) in bright light. Pupil light reaction (PLR) had a mean (SD) amplitude of 1.38 mm (0.27) and latency of 250.34 milliseconds (28.58). Pupil size and PLR were not associated with iris colour, intraocular pressure or refractive error, but were associated with age (diameter beta = -0.02, p = 0.016, constriction amplitude beta = -0.01, p < 0.001, velocity beta = 0.03, p < 0.001, and latency beta = 0.98, p < 0.001). In darkness the resting pupil size showed a MZ intraclass correlation coefficient of 0.85, almost double that of DZ (0.44), suggesting strong additive genetic effects, with the most parsimonious model estimating a heritability of 86% [95% confidence interval (CI) 79-90%] with 14% (95% CI 10-21%) explained by unique environmental factors. PLR amplitude, latency and constriction velocity had estimated heritabilities of 69% (95% CI 54-79%), 40% (95% CI 21-56%), and 64% (95% CI 48-75%), respectively. Conclusion: Genetic effects are key determinants of resting pupil size and reactivity. Future studies to identify these genetic factors could improve our understanding of variation in pupil size and pupillary reactions in health and disease

The physical and mental burden of dry eye disease:A large population-based study investigating the relationship with health-related quality of life and its determinants

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

Medication use and dry eye symptoms:A large, hypothesis-free , population-based study in the Netherlands

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