Search Results (13)

Background: Sjögren’s syndrome (SS) is a multifaceted clinical condition characterized by various features, including ocular dryness (OD), which plays a substantial role in shaping the clinical presentation of the disease and has detrimental effects on quality of life. Recent research has acknowledged the advantages of the Mediterranean diet (MD) for its positive impact on various autoimmune diseases. This study aims to investigate the correlation between the severity of ocular symptoms in individuals with SS and adherence to the MD. Methods: This was a cross-sectional observational study of previously diagnosed SS patients recruited from the histopathological and immunological archives of a university hospital. The data were collected through a telephone questionnaire, including demographic and disease data, the Ocular Surface Disease Index (OSDI) score to evaluate the OD severity, and the Mediterranean Diet Adherence Screener (MEDAS) score to determine adherence to the MD. The primary outcome of the study, the correlation between OSDI and MEDAS scores, was evaluated using Spearman’s correlation coefficient. Results: The study included 114 patients, with a mean age of 51 (±13.4) years and a female proportion of 86%. OD was documented in 80.7% of the patients. The median OSDI and MEDAS scores were 23 (IQR 10–40) and 8 (IQR 5–11), respectively. A strong negative correlation was observed between the MEDAS and the OSDI scores (ρ = −0.73, p < 0.01). Additionally, there was a significant negative relationship between the richness of diet in fatty acids and the OSDI score (ρ = −0.67, p < 0.01). Conclusions: The study results suggest an association between lower OD severity in patients with SS and adherence to the MD, particularly the components related to polyunsaturated fatty acids consumption. This approach may serve as a complementary strategy with multiple health benefits, alongside conventional treatment options. Full article

Dry eye disease (DED), also known as keratoconjunctivitis sicca, is a multifactorial ocular disease characterized by tear film insufficiency due to diverse etiologies including aging, incomplete and infrequent blinking, hormonal changes, medications, and systemic diseases. Classified into aqueous-deficient dry eye (ADDE), evaporative dry eye (EDE), and mixed subtypes, DED presents with symptoms such as irritation, stinging, redness, foreign body sensation, sensitivity to light, and blurred or fluctuating vision. While rare, severe cases may lead to vision loss. With its rising global prevalence across age groups, DED poses a significant public health challenge. Primary care physicians (PCPs), often the first point of contact for DED patients, require timely screening and management strategies. This review explores the epidemiology, pathophysiology, clinical manifestations, diagnosis, and management of DED, emphasizing practical approaches for PCPs. This narrative review was conducted by searching MEDLINE, PubMed, and Google Scholar databases for relevant articles. Diagnostic approaches, including detailed history taking, patient-reported questionnaires, differential diagnosis, and assessments are discussed alongside management strategies, including symptomatic ophthalmic treatment, risk factor mitigation (e.g., reduced digital device screen time), prevention, and nutrition. By providing a synopsis of early symptoms that PCPs are often the first to encounter, practical approaches to screening and managing DED in the primary care setting, and guidelines on when to refer to specialty care, this comprehensive review aims to equip PCPs with the knowledge to improve DED screening and optimize patient outcomes. Full article

Background: Although autoimmune complications of COVID-19 have aroused concerns, there is no consensus on its ocular complications. Sjögren’s syndrome is an autoimmune disease accompanied by the ocular abnormality keratoconjunctivitis sicca (SS-KCS), which may be influenced by COVID-19. Thereby, we explored the possible interaction between COVID-19 and SS-KCS, and we aimed to elucidate the potential correlated mechanism. Methods: Differentially expressed genes (DEGs) in COVID-19 and SS-KCS transcriptome data obtained from the gene expression omnibus database were identified, and COVID-19-related genes were screened using weighted gene coexpression network analysis. Common genes were verified using four machine-learning diagnostic predictors. The clinical relationship between the two common hub genes of COVID-19 was analyzed. Finally, the immune cell types infiltrating the microenvironment in the COVID-19 dataset were analyzed using CIBERSORT, and the interrelation between key genes and differentially infiltrating immune cells was verified via Pearson correlation. Results: Ten potential primary hub mRNAs were screened by intersecting the COVID-19 DEGs, SS-KCS DEGs, and WGCNA genes. After a multifaceted evaluation using four mainstream machine-learning diagnostic predictors, the most accurate and sensitive random forest model identified CR1 and TAP2 as the common hub genes of COVID-19 and SS-KCS. Together with the clinical information on COVID-19, the expression of CR1 and TAP2 was significantly correlated with the status and severity of COVID-19. CR1 and TAP2 were significantly positively correlated with M0 and M2 macrophages, neutrophils, and CD4+ memory resting T cells and negatively correlated with activated NK cells, monocytes, and CD8+ T cells. Conclusions: We validated the hub genes associated with both COVID-19 and SS-KCS, and we investigated the immune mechanisms underlying their interaction, which may help in the early prediction, identification, diagnosis, and management of SARS-CoV-2 infection-related SS-KCS syndrome or many other immune-related complications in the long COVID period. Full article

Juvenile primary Sjögren syndrome (pSS) with renal involvement is extremely rare, reported approximately in 50 children, predominantly girls. Here, we present the first reported case of a male child with juvenile pSS with ocular surface disease (previously keratoconjunctivitis sicca), submandibular salivary gland involvement, and tubulointerstitial nephritis. First, two symptoms were clinically apparent at presentation. We illustrate here that kidney involvement in pSS should be actively looked for, as juvenile pSS may be associated with asymptomatic renal involvement. Immunophenotyping of peripheral blood cells using multicolor flow cytometry revealed at the time of diagnosis changes in both adaptive (T memory cells and B memory cells), and innate immunity (an increased activation of natural killer cells, as well as monocytes and neutrophils, and an increased representation of intermediate monocytes). Our case report points to the importance of kidney examination, early diagnosis and therapy in juvenile pSS, as well as highlights international collaboration to obtain more data for this rare disease. Full article

The EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI), and other patient-reported outcomes (PROs), such as the visual analog scale (VAS) for symptoms and EULAR sicca score (ESS), are used to assess the disease activity of primary Sjögren’s syndrome (pSS). Recently, Clinical ESSDAI (ClinESSDAI) and Clinical Trials ESSDAI (ClinTrialsESSDAI) were developed for objective clinical disease activity indexes. However, the relationship of ClinESSDAI and ClinTrialsESSDAI with PROs as well as that between ESSPRI and other PROs and the objective parameters of glandular function in pSS have not been established. Herein, we investigated the correlation of ESSPRI and other PROs with the objective parameters of glandular function and the relationship of PROs with ClinESSDAI and ClinTrialsESSDAI in 66 patients with pSS. Correlations were calculated with Spearman’s correlation coefficient. ClinTrialsESSDAI was correlated with ESSPRI, dryness (ESSPRI-Dryness), fatigue, and pain domains of ESSPRI, VAS for oral dryness (oral-VAS), and patient’s global assessment. Although ESSPRI did not correlate with the objective parameters of glandular function, ESSPRI-Dryness, ESS, and oral- and ocular-VAS did. These results suggest that ESSPRI-Dryness, ESS, and VAS for symptoms, but not ESSPRI, reflect the glandular dysfunction and that ClinTrialsESSDAI correlates with PROs for dryness in pSS. Full article

Purpose: The aim of the study was to compare the difference in composition between 100% autologous serum (AS) and 100% platelet-rich plasma (PRP) eye drops and assess their impact on the clinical outcomes after the treatment of severe dry eye (DE) in primary Sjogren Syndrome patients (pSS). Materials and Methods: This is an interventional, non-randomized, comparative, three-month study. 22 patients with severe DE in pSS were treated with 100% AS (22 eyes) and 100% PRP (22 eyes) eye drops 5 times per day in monotherapy mode. The quantifications of growth factors (GFs) such as fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), nerve growth factor (NGF), transforming growth factor (TGF-b), insulin-like growth factor (IGF), fibronectin, and substance p in hemoderivates were done. The main outcome measures were: Ocular Surface Disease Index (OSDI), Best Corrected Visual Acuity (BCVA), the Schirmer test, tear break-up time (TBUT), corneal and conjunctival staining according to the Oxford scale, conjunctival hyperaemia, and Meibomian gland parameters. The results were compared at baseline, 1 month, and 3 months following the treatment. The clinical results were correlated with the concentration of GFs in the biological tear substitutes. Results: Significant differences were observed in the concentration of FGF (4.42 ± 0.86 vs. 15.96 ± 7.63, p < 0.0001), EGF (4.98 ± 0.97 vs. 39.06 ± 20.18, p < 0.0001), fibronectin (929.6 ± 111.5 vs. 823.64 ± 98.49, p = 0.0005), VEGF (175.45 ± 65.93 vs. 717.35 ± 488.15, p < 0.0001), PDGF AB (619.6 ± 117.30 vs. 349.66 ± 79.82, p < 0.0001), NGF (85.22 ± 23.49 vs. 8.29 ± 9.06, p < 0.0001), PDGF (935.38 ± 434.26 vs. 126.66 ± 54.41, p < 0.0001), substance p (112.58 ± 27.28 vs. 127.51 ± 26.56, p = 0.0125) in PRP compared to AS. The level of TGF-β was undoubtedly higher in AS than in PRP (1031.37 ± 330.23 vs. 726.03 ± 298.95, p = 0.0004). No significant differences between AS and PRP were observed in the concentration of IGF. Therapy with blood products relieved the signs and symptoms in pSS DE patients. There was a statistically significant improvement in BCVA, the Schirmer test, TBUT, Meibomian gland parameters, and the reduction of the OSDI scores, Oxford staining, and conjunctiva hyperaemia in each of the groups. However, the clinical changes were more significant in the PRP group. There were numerous correlations between the level of GFs and the mean change in clinical outcomes. No adverse events were reported. Conclusions: Despite the fact that blood derivatives differ in composition, they seem to be effective and safe in the treatment of severe DE in pSS patients. The signs and symptoms of DE were reduced in both groups, but only the mean change in OSDI was statistically significant. A greater reduction in OSDI scores was observed in the PRP group. The obtained results and the composition of haemoderivates may indicate the superiority of PRP in relieving the symptoms of DE in pSS patients compared to AS. Full article

Ocular diseases have a strong impact on individuals, the effects of which extend from milder visual impairment to blindness. Due to this and to their prevalence, these conditions constitute important health, social and economic challenges. Thus, improvements in their early detection and diagnosis will help dampen the impact of these conditions, both on patients and on healthcare systems alike. In this sense, identifying tear biomarkers could establish better non-invasive approaches to diagnose these diseases and to monitor responses to therapy. With this in mind, we developed a solid phase capture assay, based on antibody microarrays, to quantify S100A6, MMP-9 and CST4 in human tear samples, and we used these arrays to study tear samples from healthy controls and patients with Sjögren’s Syndrome, at times concomitant with rheumatoid arthritis. Our results point out that the detection of S100A6 in tear samples seems to be positively correlated to rheumatoid arthritis, consistent with the systemic nature of this autoinflammatory pathology. Thus, we provide evidence that antibody microarrays may potentially help diagnose certain pathologies, possibly paving the way for significant improvements in the future care of these patients. Full article

Pterygium and primary Sjögren’s Syndrome (pSS) share many similarities in clinical symptoms and ocular pathophysiological changes, but their etiology is unclear. To identify the potential genes and pathways related to immunity, two published datasets, GSE2513 containing pterygium information and GSE176510 containing pSS information, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of pterygium or pSS patients compared with healthy control conjunctiva, and the common DEGs between them were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted for common DEGs. The protein–protein interaction (PPI) network was constructed using the STRING database to find the hub genes, which were verified in clinical samples. There were 14 co-upregulated DEGs. The GO and KEGG analyses showed that these common DEGs were enriched in pathways correlated with virus infection, antigen processing and presentation, nuclear factor-kappa B (NF-κB) and Th17 cell differentiation. The hub genes (IL1R1, ICAM1, IRAK1, S100A9, and S100A8) were selected by PPI construction. In the era of the COVID-19 epidemic, the relationship between virus infection, vaccination, and the incidence of pSS and pterygium growth deserves more attention. Full article

In vivo confocal microscopy (IVCM) imaging is increasingly popular in ocular surface disease diagnosis and management. We conducted a systematic review to update the use of IVCM in the diagnosis and treatment of dry eye and meibomian gland dysfunction (MGD). A literature review was conducted on IVCM studies in MGD, dry eye disease, systemic disease causing dry eye, dry eye in glaucoma patients, contact lens-associated ocular conditions, graft-versus-host disease, and Sjogren’s syndrome-related dry eye. The articles were identified through PubMed and a total number of 63 eligible publications were analyzed in detail. All primary research studies on confocal microscopy on dry eye and related conditions from 2017 onwards were included. The reports were reviewed for their contribution to the existing literature as well as potential biases and drawbacks. Despite limitations such as small field of view, lack of population-based norms, and lack of standardization of image acquisition, interpretation, and quantification, IVCM is useful as a complementary technique for clinical diagnosis in various ocular surface disorders related to dry eye. With advances in hardware and software in the near future, it has the potential for further practical impact. Full article

Purpose: To evaluate the effectiveness of different treatment modalities for dry eye in primary Sjögren’s syndrome with their potential overlapping influences. Methods: This study included 199 patients with newly diagnosed primary Sjögren’s syndrome from 2005 to 2020. Various treatment modalities for primary Sjögren’s syndrome were compared. Improvement of corneal staining based on Sjögren’s International Collaborative Clinical Alliance (SICCA) scores was the primary outcome. Results: The average follow-up period was 5.4 ± 3.1 (range, 2.0–14.1) years. Analysis of the individual treatments showed that punctal plug insertions in the lower and upper eyelids were strongly associated with improvement of SICCA scores (β = 2.70 and 1.80, p < 0.001 and <0.001, respectively). With ocular surface inflammation, corneal staining scores improved significantly with steroid eye drops. Prednisolone (1%) had the strongest association with improvement of corneal staining scores (β = 1.48, p < 0.001); this was based on the frequency of administration. Without ocular surface inflammation, diquafosol (3%), carbomer gel, and lanolin ointment were effective (β = 1.37, 1.06, and 1.17; p = 0.003, 0.003, and <0.001, respectively). Conclusions: Punctal plug insertion, primarily targeting aqueous deficiency, is the mainstay of the treatment for dry eye in primary Sjögren’s syndrome even in the presence of ocular surface inflammation. Furthermore, the effectiveness of treatment modalities for dry eye in primary Sjögren’s syndrome was dependent on the presence of ocular surface inflammation. Full article

Sjögren’s syndrome (SS) is a chronic, progressive, inflammatory, autoimmune disease, characterized by the lymphocyte infiltration of exocrine glands, especially the lacrimal and salivary, with their consequent destruction. The onset of primary SS (pSS) may remain misunderstood for several years. It usually presents with different types of severity, e.g., dry eye and dry mouth symptoms, due to early involvement of the lacrimal and salivary glands, which may be associated with parotid enlargement and dry eye; keratoconjunctivitis sicca (KCS) is its most common ocular manifestation. It is still doubtful if the extent ocular surface manifestations are secondary to lacrimal or meibomian gland involvement or to the targeting of corneal and conjunctival autoantigens. SS is the most representative cause of aqueous deficient dry eye, and the primary role of the inflammatory process was evidenced. Recent scientific progress in understanding the numerous factors involved in the pathogenesis of pSS was registered, but the exact mechanisms involved still need to be clarified. The unquestionable role of both the innate and adaptive immune system, participating actively in the induction and evolution of the disease, was recognized. The ocular surface inflammation is a central mechanism in pSS leading to the decrease of lacrimal secretion and keratoconjunctival alterations. However, there are controversies about whether the ocular surface involvement is a direct autoimmune target or secondary to the inflammatory process in the lacrimal gland. In this review, we aimed to present actual knowledge relative to the pathogenesis of the pSS, considering the role of innate immunity, adaptive immunity, and genetics. Full article

Dry eye symptoms can negatively affect the psychological, physical, and social functioning, which can potentially impair the health-related quality of life. This review evaluated the association between autoimmune related dry eye in the absence of significant ocular surface co-morbidities and mental health. This review found a significantly higher prevalence of mental health disorders (such as depression and anxiety) in systemic lupus erythematous, rheumatoid arthritis, systemic sclerosis, Behcet’s disease, and primary Sjogren’s syndrome patients when compared to the general population. Moreover, patients with depression and anxiety interpret ocular sensations differently than healthy controls and the perception of dry eye symptoms can be influenced by their mood. Somatization is common in depression, and this could influence the perception of ocular discomfort. Anti-depressants and anxiolytics with their potential side effects on the tear film status may also contribute or aggravate the dry eye symptoms in these patients. Although ophthalmologists manage the dry eye disease, as per standardized algorithms, they should be mindful of different ocular sensation interpretation and coexistent mental health issues in a large number of this patient group and initiate a multidisciplinary management plan in certain cases. While rheumatologists look after their autoimmune condition, it may be worth liaising with GP and/or psychiatrist colleagues in order to address their neuropathic type pain and mental health co-morbidities. Full article

Thrombospondin-1-deficient (TSP-1^−/−) mice are used as an animal model of Sjögren’s Syndrome because they exhibit many of the symptoms associated with the autoimmune type of dry eye found in primary Sjögren’s Syndrome. This type of dry eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, and is thought to involve dysfunction of the complex neuronal reflex arc that mediates tear production in response to noxious stimuli on the ocular surface. This study characterizes the structural and functional changes to the corneal nerves that are the afferent arm of this arc in young and older TSP-1^−/− and wild type (WT) mice. The structure and subtype of nerves were characterized by immunohistochemistry, in vivo confocal microscopy, and confocal microscopy. Cytokine expression analysis was determined by Q-PCR and the number of monocytes was measured by immunohistochemistry. We found that only the pro-inflammatory cytokine MIP-2 increased in young corneas of TSP-1^−/− compared to WT mice, but tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) all increased in older TSP-1^−/− mouse corneas. In contrast, CD11b+ pro-inflammatory monocytes did not increase even in older mouse corneas. Calcitonin gene-related peptide (CGRP)-, but not Substance P (SubP)-containing corneal nerves decreased in older, but not younger TSP-1^−/− compared to WT mouse corneas. We conclude that CGRP-containing corneal sensory nerves exhibit distinct structural deficiencies as disease progresses in TSP-1^−/− mice, suggesting that: (1) TSP-1 is needed for the development or repair of these nerves and (2) impaired afferent corneal nerve structure and hence function may contribute to ocular surface dysfunction that develops as TSP-1^−/− mice age. Full article