Characterization of Lipids in Saliva, Tears and Minor Salivary Glands of Sjögren's Syndrome Patients Using an HPLC/MS-Based Approach.

The diagnostic work-up of primary Sjögren's syndrome (pSS) includes quantifying saliva and tear production, evaluation of autoantibodies in serum and histopathological analysis of minor salivary glands. Thus, the potential for further utilizing these fluids and tissues in the quest to find better diagnostic and therapeutic tools should be fully explored. Ten samples of saliva and tears from female patients diagnosed with pSS and ten samples of saliva and tears from healthy females were included for lipidomic analysis of tears and whole saliva using high-performance liquid chromatography coupled to time-of-flight mass spectrometry. In addition, lipidomic analysis was performed on minor salivary gland biopsies from three pSS and three non-SS females. We found significant differences in the lipidomic profiles of saliva and tears in pSS patients compared to healthy controls. Moreover, there were differences in individual lipid species in stimulated saliva that were comparable to those of glandular biopsies, representing an intriguing avenue for further research. We believe a comprehensive elucidation of the changes in lipid composition in saliva, tears and minor salivary glands in pSS patients may be the key to detecting pSS-related dry mouth and dry eyes at an early stage. The identified differences may illuminate the path towards future innovative diagnostic methodologies and treatment modalities for alleviating pSS-related sicca symptoms.

Culture- and non-culture-based approaches reveal unique features of the ocular microbiome in dry eye patients.

PURPOSE: The purpose of this study was to investigate the ocular microbiome in individuals with dry eye disease and to identify features of their ocular microbiome of possible health and diagnostic significance. METHODS: Conjunctival samples were collected from both eyes in duplicate from 91 individuals (61 dry eye, 30 healthy) and used for both culture-dependent and culture-independent analyses. Samples were either analysed using next generation sequencing (V3-V4 16S rDNA) or inoculated on a wide range of agar types and grown under a broad range of conditions to maximize recovery. Isolates were identified by partial sequencing of the 16S rDNA and rpoB genes and tested for antibiotic susceptibility. We applied a L2-regularized logistic regression model on the next generation sequencing data to investigate any potential association between severe dry eye disease and the ocular microbiome. RESULTS: Culture-dependent analysis showed the highest number of colony forming units in healthy individuals. The majority of isolates recovered from the samples were Corynebacterium, Micrococcus sp., Staphylococcus epidermidis, and Cutibacterium acnes. Culture independent analysis revealed 24 phyla, of which Actinobacteria, Firmicutes and Proteobacteria were the most abundant. Over 405 genera were detected of which Corynebacterium was the most dominant, followed by Staphylococcus and Cutibacterium. The L2-regularized logistic regression model indicated that Blautia and Corynebacterium sp. may be associated with severe DED. CONCLUSIONS: Our study indicates that the ocular microbiome has characteristic features in severe DED patients. Certain Corynebacterium species and Blautia are of particular interest for future studies.

Topical glaucoma medications - Possible implications on the meibomian glands.

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

Response predictors of a topical corticosteroid-based regimen for dry eyes: A real-life study.

PURPOSE: To examine the effectiveness and identify clinical response predictors of a short corticosteroid-based regimen consisting of topical preservative-free 0.1% dexamethasone (Monopex®, Théa Laboratories) in conjunction with artificial tears (AT) for dry eyes in a real-life clinical setting. METHODS: Patients were recruited from the Norwegian Dry Eye Clinic and were allowed to use ATs of their own choice in addition to the prescribed 14-day topical dexamethasone course. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire (DEQ-5), Schirmer test (ST), fluorescein tear film break-up time (FBUT), ocular surface staining (OSS), meibum expressibility (ME), meibum quality (MQ), number of expressible meibomian glands among the central eight glands in the lower lids (NMG) and intraocular pressure (IOP) were measured at baseline and at 1-month follow-up. The average values of clinical parameters from both eyes were used for analyses. A paired t-test and a significance value of p < 0.05 were used for statistical analyses. Associations between sex, age, baseline values and the changes after the intervention (Δ) were explored using linear regression. RESULTS: A total of 167 patients (124 women, mean age 54 years ±17 (standard deviation)) were included. One month after initiation of intervention, OSDI and DEQ5 scores improved from 39.5 ± 22.1 to 31.4 ± 21.3 (p < 0.001) and from 12.6 ± 4.2 to 11.0 ± 4.6 (p < 0.001), respectively. OSS improved from 2.2 ± 1.4 to 1.8 ± 1.5 (p < 0.001), NMG increased from 4.8 ± 2.2 to 5.1 ± 2.2 (p < 0.05), while IOP decreased from 12.9 ± 3.3 to 12.4 ± 3.5 mmHg (p < 0.05). Significant associations were found between the change in symptoms and objective measures of DED (ΔOSDI, ΔDEQ5, ΔOSS, ΔFBUT, ΔNMG, ΔMQ) and their respective baseline values (OSDI, DEQ5, OSS, FBUT, NMG, MQ). The remaining tests did not show statistically significant changes. CONCLUSION: Improvement in dry eye symptoms and signs were observed following a short course of topical, preservative-free 0.1% dexamethasone treatment in combination with AT. Individuals exhibiting more pronounced symptoms and signs witnessed the most profound improvements with the treatment regimen, suggesting that poor baseline parameters may serve as response predictors of the treatment regimen. While the real-life data presented herein are valuable, the conclusions are limited by the inherent biases of a non-controlled study.

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

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

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.

Using machine learning model explanations to identify proteins related to severity of meibomian gland dysfunction.

Meibomian gland dysfunction is the most common cause of dry eye disease and leads to significantly reduced quality of life and social burdens. Because meibomian gland dysfunction results in impaired function of the tear film lipid layer, studying the expression of tear proteins might increase the understanding of the etiology of the condition. Machine learning is able to detect patterns in complex data. This study applied machine learning to classify levels of meibomian gland dysfunction from tear proteins. The aim was to investigate proteomic changes between groups with different severity levels of meibomian gland dysfunction, as opposed to only separating patients with and without this condition. An established feature importance method was used to identify the most important proteins for the resulting models. Moreover, a new method that can take the uncertainty of the models into account when creating explanations was proposed. By examining the identified proteins, potential biomarkers for meibomian gland dysfunction were discovered. The overall findings are largely confirmatory, indicating that the presented machine learning approaches are promising for detecting clinically relevant proteins. While this study provides valuable insights into proteomic changes associated with varying severity levels of meibomian gland dysfunction, it should be noted that it was conducted without a healthy control group. Future research could benefit from including such a comparison to further validate and extend the findings presented here.

Topical glaucoma medications - Clinical implications for the ocular surface.

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

Predicting an unstable tear film through artificial intelligence.

Dry eye disease is one of the most common ophthalmological complaints and is defined by a loss of tear film homeostasis. Establishing a diagnosis can be time-consuming, resource demanding and unpleasant for the patient. In this pilot study, we retrospectively included clinical data from 431 patients with dry eye disease examined in the Norwegian Dry Eye Clinic to evaluate how artificial intelligence algorithms perform on clinical data related to dry eye disease. The data was processed and subjected to numerous machine learning classification algorithms with the aim to predict decreased tear film break-up time. Moreover, feature selection techniques (information gain and information gain ratio) were applied to determine which clinical factors contribute most to an unstable tear film. The applied machine learning algorithms outperformed baseline classifications performed with ZeroR according to included evaluation metrics. Clinical features such as ocular surface staining, meibomian gland expressibility and dropout, blink frequency, osmolarity, meibum quality and symptom score were recognized as important predictors for tear film instability. We identify and discuss potential limitations and pitfalls.

The role of meibography in ocular surface diagnostics: A review.

The meibomian glands are lipid-secreting glands located in the tarsal plates, whose secretory products cover the tear film, thereby reducing evaporation as well as ensuring lubrication of the ocular surface. The meibomian glands can be visualized at different levels of magnification by infrared meibography, laser confocal microscopy, and optical coherence tomography. These imaging modalities have been subject to much research and progress in clinical practice and have shaped our current understanding of meibomian glands in health and disease. In this review, we explore the evolution of meibography over the past decades, the major contributions of various meibographic modalities, and discuss their clinical significance.

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.

Intense pulsed light treatment in meibomian gland dysfunction: A concise review.

PURPOSE: To review the published literature related to application of intense pulsed light (IPL) for treating meibomian gland dysfunction (MGD). METHODS: The literature search included the PubMed database and used the keywords "Intense Pulsed Light and Meibomian Gland Dysfunction". RESULTS: IPL is a new instrumental treatment modality for MGD. This treatment modality was originally developed for use in dermatology and was later adopted in ophthalmology for treating MGD. IPL therapy for MGD can improve tear film stability, meibomian gland functionality, as well as subjective feeling of ocular dryness. However, in the reviewed literature, there was great variability in patient selection, evaluation criteria, and treatment protocols and durations. CONCLUSION: Numerous studies report that IPL is effective for treating MGD and a safe procedure. There is great potential for further improvements to the procedure, as large comparative studies employing different treatment modalities are lacking.