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.

Exploring oral health indicators, oral health-related quality of life and nutritional aspects in 23 medicated patients from a short-term psychiatric ward.

Background: Patients suffering from psychiatric disorders face many difficulties due to their condition, medications and lifestyle. Oral health and nutrition may be affected, further complicating their lives. Our aim was to provide in-depth information on oral health and nutritional factors in a small group of patients in short-term psychiatric ward. Methods: Twenty-three patients (mean age 36, average medications five) were recruited during short-term hospitalization in a psychiatric ward. Inclusion criteria: anxiety, psychosis and/or depression, and use of at least one antidepressant or anxiolytic/antipsychotic drug with xerostomia as a known side effect. Subjective oral dryness was evaluated using the Shortened Xerostomia Inventory (SXI). Oral examination included Clinical Oral Dryness Score (CODS), secretion of unstimulated (UWS) and stimulated whole saliva (SWS), and evaluation of dental, gingival, and periodontal status. Self-reported complaints of oral disorders were recorded. The Oral Health Impact Profile-14 (OHIP-14) was used to explore oral health-related quality of life. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment Short Form (PG-SGA-SF), and diet quality was assessed using the Mediterranean diet score (KIDMED). Results: Compared to healthy controls, the patients had significantly higher SXI scores and CODS, and SWS secretion was lower. Complaints of dysgeusia and halitosis were significantly more frequent among patients. Gingivitis was more common in patients. OHIP-14 scores were much higher in the patients, and they reported significantly poorer oral and general health. Most patients lacked a regular meal pattern. Very low diet quality was observed in five patients, while improvements were needed in twelve. "Dry mouth" and "No appetite, just did not feel like eating" were the most common symptoms preventing patients from eating enough. The PG-SGA-SF symptoms component score showed a strong negative correlation with self-reported oral health, and a strong positive correlation with OHIP-14. Conclusion: This relatively small group of patients in short-term psychiatric ward had both reduced oral health and poor oral health-related quality of life. Furthermore, their nutritional intake was affected by their oral health problems. Although larger groups need to be studied, these findings indicate that oral health and nutrition should be evaluated and adjusted in these patients to improve their overall care.

The relationship between ocular and oral dryness in a cohort from the 65-year-old population in Norway.

In the present study, the relationship between dry eyes and dry mouth was explored in 150 65-year-old subjects randomly selected from the general population in Oslo, Norway. The number of drugs, including xerogenic drugs, and current and previous systemic diseases were recorded. Ocular parameters recorded were the McMonnies Dry Eye Questionnaire, the Ocular Surface Disease Index, the Schirmer I Test, tear film break-up time and ocular surface staining. The oral parameters were xerostomia frequency, Summated Xerostomia Inventory, Clinical Oral Dryness Score, and unstimulated and stimulated whole saliva. The participants with current or previous systemic diseases had significantly more ocular and oral symptoms and significantly more oral clinical findings than the participants without a history of disease. Moreover, correlation and factor analyses demonstrated an association between subjective ocular and oral parameters. A significant correlation between the total number of drugs and the presence of ocular and oral symptoms was also noted. When the participants were categorized based on their ocular symptoms, poorer values were found for the oral parameters among the participants more troubled with dry eyes. The results in the present study call for increased awareness and an interdisciplinary approach in matters related to dry eyes and dry mouth.

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren's Syndrome Patients.

Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers.

Saliva Metabolomics in Dry Mouth Patients with Head and Neck Cancer or Sjögren's Syndrome.

The etiology of dry mouth conditions is multi-faceted. Patients radiated after head and neck cancer (HNC) and those with primary Sjögren's syndrome (pSS) share many of the same symptoms despite different causes. With the aim of better understanding the pathophysiology and biochemical processes behind dry mouth with different etiologies, we investigated the metabolic profile of 10 HNC patients, 9 pSS patients and 10 healthy controls using high-performance liquid chromatography-high resolution mass spectrometry (HPLC-MS) metabolomics. Principal component analysis (PCA) revealed different metabolic profiles when comparing all subjects included in the study. Both patient groups showed higher ratios of several pyrimidine nucleotides and nucleosides when compared to controls. This finding may indicate that purinergic signaling plays a role in dry mouth conditions. Moreover, significantly increased levels of DL-3-aminoisobutyric acid were found in HNC patients when compared to controls, and a similar tendency was observed in the pSS patients. Furthermore, a dysregulation in amino acid metabolism was observed in both patient groups. In conclusion, metabolomics analysis showed separate metabolic profiles for HNC and pSS patients as compared to controls that could be useful in diagnostics and for elucidating the different pathophysiologies. The demonstrated dysregulation of pyrimidine nucleotides and levels of metabolites derived from amino acids in the patient groups should be studied further.

Morphology of Meibomian Glands in a 65-Year-Old Norwegian Population without Dry Eye Disease.

Analyses of meibography may help in the diagnosis, prevention, and management of meibomian gland dysfunction (MGD). However, there is currently a paucity of data regarding meibography analyses in the young elderly populations in the Nordic countries. In the current study, meibography of the upper and lower eyelids of 117 65-year-old residents in Oslo, Norway, who did not fulfil the diagnosis of dry eye disease (DED) were analysed. Meibomian gland (MG) dropout and tarsal areas were measured semi-automatically using ImageJ software. The relationship between morphological features of the MGs and clinical dry eye tests was examined. The median percent MG dropout was 26.1% and 40.7% in the upper and lower eyelids, respectively. There was no significant difference between males and females. None of the MG morphological parameters demonstrated significant values in discriminating abnormal dry eye symptom loads or MGD diagnosis from the normal loads. We therefore concluded that moderate MG atrophy was common among the Norwegian population of 65-year-olds without DED and showed no sexual differences. Meibography alone cannot discriminate MGD from non-MGD; thus, both morphological and functional MG tests are necessary when screening for MGD.

Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer.

Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.

Oral and ocular late effects in head and neck cancer patients treated with radiotherapy.

A broader understanding of oral and ocular late effects in head and neck cancer (HNC) patients who underwent intensity-modulated radiotherapy (IMRT) may provide valuable information in follow-up and improve quality of life. Twenty-nine HNC patients treated at least 6 months earlier and 30 age-matched controls were recruited. After completing several questionnaires: Oral Health Impact Profile-14 (OHIP-14), Shortened Xerostomia Inventory (SXI), Ocular Surface Disease Index (OSDI) and McMonnies Dry Eye questionnaire (MDEQ), participants underwent oral and ocular examinations. Oral examination included clinical oral dryness score (CODS) and secretion rates of unstimulated and stimulated saliva (UWS, SWS). Ocular examination included tear film break-up time, Schirmer test and ocular surface staining. The patients had more problems related to dry mouth than controls based on CODS and SXI, and more complaints of dry eye disease based on OSDI and MDEQ. UWS and SWS rates and oral health related quality of life were significantly lower in the patient group. Subjective oral dryness (SXI) correlated significantly with subjective ocular dryness (OSDI and MDEQ). Our study demonstrates that HNC patients treated with IMRT experience late effects in terms of xerostomia and ocular dryness underlining the importance of interdisciplinary approach in the evaluation and follow-up of HNC patients.

Cytokines Explored in Saliva and Tears from Radiated Cancer Patients Correlate with Clinical Manifestations, Influencing Important Immunoregulatory Cellular Pathways.

Although radiotherapy is a common form of treatment for head and neck cancer, it may lead to tissue damage in the salivary and lacrimal glands, possibly affecting cytokine expression in the gland fluid of treated individuals. Cytokine profiles in saliva and tear fluid of 29 radiated head and neck cancer patients and 20 controls were screened using a multiplex assay. Correlations between cytokine expression and clinical oral and ocular manifestations were examined, and cellular pathways influenced by these cytokines were assessed using the Functional Enrichment Analysis Tool. Significantly elevated cytokines identified in patient saliva were CCL21, IL-4, CX3CL1, CCL2, CXCL1 and CCL15. Many of these cytokines correlated positively with objective signs of oral dryness, and reduced saliva production in the patients. Although CCL21 and IL-4 levels were significantly lower in patient tear fluid, they correlated with subjective ocular symptoms. These increased salivary cytokines affected pro-inflammatory and apoptotic cellular pathways, including T cell signalling, several interleukin signalling pathways, TNF and TGF-ß receptor signalling, and the apoptotic p53 pathway. In conclusion, the upregulated salivary cytokines identified suggest an interplay between innate and adaptive immunity, affecting immunoregulatory cellular pathways. Whether this is due to late effects of radiotherapy or tissue repair remains to be investigated.