Lacrimal Gland Research Articles

IgG4-related Breast Disease: Review of the Literature

IgG4-related disease (IgG4-RD) is a rare illness with inflammatory and fibrotic changes in affected organs such as pancreas, thyroid, salivary or lacrimal glands, and retroperitoneal space; rarely other organs may be involved. IgG4-related breast disease (IgG4-BD) is very rare and generally presents as a lump or mastitis. IgG4-BD as a presenting feature of IgG4-RD is extremely rare. Hence, this paper reviews the known (n=48) IgG-BD cases reported in the literature to date. The majority of cases were diagnosed on routine mammography or during assessment for other clinically significant features. The absence of a lump border, and especially the absence of calcifications on ultrasonography, mammography, or computed tomography, is typical for IgG4-BD. Characteristic IgG4-BD pathological findings were dense lymphoplasmacytic infiltration with stromal fibrosis, and more than 10% IgG4+ plasma cells/high-power field (HPF); the mean percentage of IgG4+/IgG+ plasma cells was 54.2%, and only one-third of the patients had all “classical” signs of IgG4-BD including storiform fibrosis and obliterative phlebitis. Most of the cases had a benign course and responded to surgical excision with or without steroid therapy.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Dependent Attenuation of Tear Hyperosmolarity and Immune Cell-Driven Inflammation in the Eyes of Patients with Dry Eye Disease

Background: Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients. Methods: An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED. Results: Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications. Conclusions: MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED.

Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: case report and literature review.

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.

Non-invasive miRNAs for early detection and diagnosis of lacrimal adenoid cystic carcinoma.

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Optimizing surgical approaches for lacrimal gland adenoid cystic carcinoma to minimize cross-organ invasion.

To evaluate the outcomes of eye-sparing surgery for lacrimal gland adenoid cystic carcinoma and the impact on tumor recurrence and orbital integrity. The study enrolled four patients with recurrent lacrimal gland adenoid cystic carcinoma. The outcome focused on the relevance of the integrity of the lateral orbital wall to the occurrence of extraorbital metastasis in the local recurrence of lacrimal gland adenoid cystic carcinoma. Three patients underwent eye-sparing surgery via lateral orbitotomy without postoperative radiotherapy, and one patient who underwent eye-sparing surgery via sub-brow approach. These four patients all demonstrated a recurrence involving the invasion of extraorbital tissues as metastatic form through surgical bone seams. Preserving intact orbital bone tissue is crucial for mitigating direct cross-organ metastasis of lacrimal gland adenoid cystic carcinoma. The findings suggest avoiding the lateral orbitotomy approach with no or limited orbital bone wall invasion.

Psychological resilience in patients with primary Sjögren's syndrome: effect of involvement of major salivary and lacrimal glands.

The aim of this study was to assess whether the involvement of major salivary and lacrimal glands in primary Sjögren's syndrome (pSS) affected the psychological resilience of patients. This cross-sectional study included 116 patients with pSS. Data were collected through clinical examinations, measurement of salivary flow rates (SFRs), and from Schirmer's test, as well as from patient-reported outcome measures (PROMs), such as the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), Brief Resilience Scale (BRS), Work Productivity and Activity Impairment (WPAI), Oral Health Impact Profile-14 (OHIP-14), and the Hospital Anxiety and Depression Scale (HADS). Hyposalivation was defined as an unstimulated SFR of≤0.1mL/min. The BRS score (mean±SD=2.60±0.69) was lower in patients with recurrent parotitis (2.11±0.37) than in those without recurrent parotitis (2.67±0.86), in the whole group. In patients with an unacceptable symptom state (ESSPRI score≥5 points), a lower BRS score was observed in patients with both hyposalivation and ocular dryness (2.59±0.69) than in patients with isolated hyposalivation (2.84±0.84). The BRS score was also negatively associated with the WPAI-Daily Impairment and OHIP-14 scores in patients with hyposalivation as well as with HADS-A (the seven items of HADS relating to the anxiety dimension) and HADS-D (the seven items of HADS relating to the depression dimension) in the whole group. The results suggest that psychological resilience in pSS may be affected by recurrent parotitis, the levels of anxiety and depression, as well as hyposalivation with ocular dryness.

Axis "microbiota – gut – eye": a review

Every organ in the human body has its own microbiota, and the eye, a complex multi-component organ, is no exception. Due to the limitations of traditional methods, detailed study of the ocular microbiome began only in 2010 as part of the Eye Microbiome Project, when advances in research methods made it possible to obtain detailed data, although there had been debate previously about whether microorganisms were even able to attach to the ocular surface due to the layers of the tear film, which have antibacterial properties. The cornea, conjunctiva, lacrimal glands and tear film, meibomian glands and microbiome form the microenvironment of the ocular surface, interacting together and resisting irritants, allergens and pathogens. Homeostasis of the ocular microbiota is critical for maintaining the health of the visual organ. Most microorganisms are found on the cornea and conjunctiva, and modern research methods, including 16S rRNA sequencing, have allowed us to establish the "core" of the ocular surface microbiota, identifying the most common types: Staphylococcus, Corynebacterium, Propionibacterium, and Streptococcus, although the exact composition of the “core” remains debatable. Many factors can influence the composition of the microbiome, including age, contact lens wear, ophthalmic medications, and antibiotics. Like the microbiome of many other organs, the ocular surface microbiome is influenced by the gut microbiome: this relationship has been called the "microbiota – gut – eye" axis. Within the "gut – eye" axis, healthy gut microbiota produce short-chain fatty acids, indoles, polyamines, and other substances that have a beneficial effect on the immune system and retinal health. The state of dysbiosis leads to disruption of homeostasis, and the increasing inflammatory reaction can contribute to damage to the optic nerve and progression of eye disease. Some ophthalmologic diseases, such as diabetic retinopathy, age-related macular degradation, choroidal neovascularization, uveitis, primary open-angle glaucoma, Sjogren's syndrome, dry eye syndrome are associated with dysbiosis of the intestinal microbial composition. Correction of intestinal dysbiosis using various methods can lead to a decrease in the risk of eye diseases, although additional research is needed to discover new methods for treating ophthalmologic pathologies along the "microbiota – gut – eye" axis.

Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.

Sjögren's syndrome (SS) or Sjögren's disease (SjD) is a systemic autoimmune disease clinically manifested as sicca symptoms. This disease primarily impacts the functionality of exocrine glands, specifically the lacrimal and salivary glands (SG). SG fibrosis, an irreversible morphological change, is a severe consequence that occurs in the later stages of the disease due to sustained inflammation. However, the mechanism underlying SG fibrosis in SS remains under-investigated. Glandular fibrosis may arise from chronic sialadenitis, in which the interactions between infiltrating lymphocytes and epithelial cells potentially contributes to fibrotic pathogenesis. Thus, both immune and non-immune cells are closely involved in this process, while their interplays are not fully understood. The molecular mechanism of tissue fibrosis is partly associated with an imbalance of immune responses, in which the transforming growth factor-beta (TGF-β)-dependent epithelial-mesenchymal transition (EMT) and extracellular matrix remodeling are recently investigated. In addition, viral infection has been implicated in the pathogenesis of SS. Viral-specific innate immune response could exacerbate the autoimmune progression, resulting in overt inflammation in SG. Notably, post-COVID patients exhibit typical SS symptoms and severe inflammatory sialadenitis, which are positively correlated with SG damage. In this review, we discuss the immune and non-immune risk factors in SG fibrosis and summarize the evidence to understand the mechanisms upon autoimmune progression in SS.

Single-Cell Transcriptomics Reveals a Pivotal Role of DOCK2 in Sjögren Disease.

Sjögren disease (SjD) is an autoimmune condition characterized by the dysfunction of the salivary and lacrimal glands. The study aimed to decipher the pathogenic cell populations and their immunologic pathways in the salivary glands. We further determined the therapeutic effect of inhibiting dedicator of cytokinesis 2 (DOCK2) shared by novel clusters of CD8+ T cells in an SjD mouse model. This study employed single-cell RNA sequencing to examine the composition and dynamics of immune cells in the salivary glands of SjD mice. By analyzing the transcriptomic data and employing clustering analysis, a specific target was identified, leading to the treatment of mice with a targeted inhibitor. The results showed diverse immune cell types, including B cells, CD4+ T cells, CD8+ T cells, macrophages, and natural killer cells. We identified specific clusters possessing phenotypic characteristics of immune cell subpopulations, thereby showing specific genes/pathways associated with the disease. The most striking finding was the elevated expression of DOCK2 in CD8+ T cells in the SjD model. This discovery is significant because subsequent treatment with a DOCK2 inhibitor 4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP) led to a marked amelioration of SjD signs. The effectiveness of DOCK2 inhibition in alleviating SjD signs highlights the potential of DOCK2 as a therapeutic target, opening new avenues for treatment strategies that could modulate the immune response more effectively in SjD.

Umbilical Cord Blood Platelet Lysate Eyedrops for the Treatment of Severe Ocular Surface Disorders in Graft vs. Host Disease Patients: Clinical Study

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD.

Magnetic resonance diffusion-weighted imaging in lacrimal gland lymphoma versus inflammation: A comparative study.

To determine the role of diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) in differentiating the inflammatory process and malignant lymphoma of the lacrimal gland. A retrospective analysis of all subjects who underwent lacrimal gland biopsy and magnetic resonance (MR) imaging with DWI sequences during a 10-year period at the Sheba Medical Center, Israel. The lacrimal glands' ADC values were documented bilaterally by blinded observers and correlated with the final histology verified diagnoses. Twenty-eight patients were included, with 19 females (68%) with a mean ± SD age of 48.1 ± 25.7 years. The right orbit was involved in 14 cases (50%) and the left in 13 (46%); one patient (4%) had bilateral involvement. Seventeen cases (61%) had a final diagnosis of idiopathic inflammation or dacryoadenitis, and six cases (21%) were diagnosed with lymphoma. Additional diagnoses included pleomorphic adenoma in 3 (11%), adenoid cystic carcinoma, and solitary fibrous tumor. Lower mean ADC values were observed in the lymphoma versus inflammatory group (1.03 × 10-3 Vs. 1.45 × 10-3, P = 0.02). Restricted diffusion on MR imaging can serve as a diagnostic tool in the differentiation between inflammatory processes of the lacrimal gland and lymphoma.

BMAL1 Deficiency Provokes Dry Mouth and Eyes by Down-regulating ITPR2/3

Secretory glands, responsible for tears and saliva production, play essential roles in maintaining ocular and oral well-being. Disruptions in gland secretion can arise from various factors, including rhythm disturbances associated with sleep disorders. However, the underlying mechanisms governing these disruptions remain largely unexplored. We demonstrate that BMAL1, a core component of the circadian system, plays a critical role in regulating secretory gland secretion. Loss of BMAL1 induces vacuolation and atrophy phenotypes in acinar cells, subsequently leading to cell apoptosis and gland hypofunction, but does not cause Sjogren's syndrome, which is characterized by localized inflammatory cell infiltration. Mechanically, BMAL1 directly modulates the transcription of ITPR2 and ITPR3, thereby altering the secretion of Lactoferrin and Lysozyme. Restoration of ITPR2 and ITPR3 expression in Bmal1-deficient rats effectively alleviated the symptoms of lacrimal and parotid glands secretory dysfunction and significantly reduced dry mouth and dry eye conditions in rhythm-disordered rats. These findings highlight the essential role of BMAL1 in regulating salivary and lacrimal gland secretion and suggest a novel therapeutic approach for treating dry mouth and dry eyes associated with rhythm disorders.

Cytarabine chemotherapy induces meibomian gland dysfunction

PurposeCytarabine (Ara-C) chemotherapy causes symptoms resembling meibomian gland dysfunction (MGD), suggesting potential associations between Ara-C and MGD. In this study, the pathological effects of Ara-C on MGD were investigated in a rodent model. MethodsMice received Ara-C with or without rosiglitazone (PPARγ agonist) for 7 consecutive days. Slit-lamp biomicroscope was used for ocular examinations. Immunofluorescence detected acinar cell proliferation, differentiation, and ductal keratinization in the meibomian gland (MG). Lipid accumulation was evaluated by Oil Red O and LipidTox staining. Lipogenic status, FoxO1/FoxO3a cellular localization, and oxidative stress were visualized via immunohistochemistry. Western blotting assessed relative protein expression and AKT/FoxO1/FoxO3a pathway phosphorylation. ResultsAra-C (50 mg/kg) did not affect mouse survival but induced damage to ocular surface microenvironment, including corneal epithelial defects, MG orifice plugging and acinar dropout, and lacrimal gland (LG) dysfunction. Ara-C intervention inhibited proliferation and caused progenitor loss in the MG, as evidenced by reduced PCNA + labeling and P63+/Lrig1+ basal cell numbers. The MG ducts of Ara-C-treated mice exhibited marked dilatation, lipid deposition, and hyperkeratinization (K1/K10 overexpression). Ara-C disrupted MG lipid metabolism by downregulating PPARγ and its downstream lipogenic targets AWAT2/SOAT1/ELOVL4 and upregulating HMGCR. Dephosphorylation of AKT and the subsequent nuclear translocation of FoxO1/FoxO3a contributed to Ara-C-induced PPARγ downregulation. Ara-C triggered oxidative stress with increases in 4-HNE and 8-OHdG and Keap1/Nrf2/HO-1/SOD1 axis dysregulation. Rosiglitazone treatment ameliorated MGD-associated pathological manifestations, LG function, MG lipid metabolism, and oxidative stress in Ara-C-exposed mice. ConclusionsSystemic Ara-C chemotherapy exerted topical cytotoxic effects on the ocular surface, and PPARγ restoration by rosiglitazone mitigated Ara-C-induced MGD alterations.

A rare pathology that mimics lung cancer: IgG4-related vasculitis.

Immunoglobulin-G4 (IgG4)-related disease is essentially a fibro-inflammatory disease that can affect any organ simultaneously or at different times. The disease usually presents with organ growth that mimics a tumour and can affect the lacrimal glands, major salivary glands, pancreas, bile ducts, retroperitoneal area, lungs, kidneys, aorta, meninges and thyroid gland. The immunopathogenesis behind this new disease has not yet been elucidated. Histopathological distinguishing features of the disease include dense lymphoplasmocytic infiltrates dominated by IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis. The likelihood of developing with immunoglobulin G4 (IgG4-RD) is a recently identified rare systemic fibroinflammatory disease with an estimated incidence of less than 1 in 100,000 people worldwide. We present our case, which was diagnosed with IGG4-related vasculitis by lung fine needle aspiration biopsy, which is very rare in the literature.

IL-37 Inhibits Inflammation of Lacrimal Gland in Dry Eye Mice via the IL-37-PTEN-NFκB Signaling Pathway

ABSTRACT Purpose This study aims to investigate the role of Interleukin-37 (IL-37) in mouse models of dry eye. Methods Two murine models of dry eye were employed in this investigation. The evaluation of the anti-inflammatory impact of IL-37 (200 μl, 10 μg/ml) on dry eye mice involved intraperitoneal injections administered once daily for 7 days. Additionally, intraperitoneal injection of VO-Ohpic trihydrate (VO, 0.25 mg/kg) in dry eye mice was performed to investigate the role of PTEN in the IL-37 anti-inflammatory signaling pathway. Tear production was assessed using phenol red cotton thread, while corneal damage was examined through sodium fluorescein staining using a slit lamp. Histological alterations in the lacrimal gland were observed through H&E staining. PAS staining was used to assess conjunctival goblet cells. The levels of NFκB-P65, p-NFκB-P65, IL-1β, IL-6, TNF-α, CD3, AQP5, α-SMA and PTEN proteins were determined via Western blotting or immunofluorescence. Results Following IL-37 treatment, both dry eye models exhibited reduced corneal fluorescence staining scores and enhanced tear production. In lacrimal gland, the expression of p-NFκB-P65, IL-1β, IL-6, CD3 and TNF-α was diminished, while PTEN, AQP5, α-SMA expression increased after IL-37 treatment in both dry eye mice. However, the intraperitoneal injection of VO significantly attenuated the anti-inflammatory effect of IL-37 on dry eye mice. Conclusion IL-37 emerges as an anti-inflammatory mediator within the lacrimal gland of dry eye mice, exerting its effects through the IL-37-PTEN-NFκB signaling pathway.

Loss of CCL28 and CXCL17 Expression and Increase in CCR1 Expression May Be Related to Malignant Transformation of LGBLEL into Lymphoma.

To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and orbital cavernous hemangioma (CH). Three cases of LGBLEL and three cases of lymphoma were randomly selected as control and experimental groups, respectively. A real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate genes associated with the chemokine signaling pathway. Immunohistochemical (IHC) staining and quantitative Western blotting (WB) were performed for precise protein quantification. Transcriptome analysis revealed differential expression of the chemokine signaling pathway between the LGBLEL and lymphoma groups, identifying ten differentially expressed genes: CCL17, VAV2, CXCR5, NRAS, HCK, RASGRP2, PREX1, GNB5, ADRBK2, and CCL22. RT-qPCR showed that, compared to the lymphoma group, the LGBLEL group had significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.001, <0.001, <0.001, <0.001, =0.020, <0.001, respectively) and lower expression of CCR1 (p = 0.002). IHC staining and quantitative analysis confirmed significant differences in protein expression between the groups for CCL28, CCR1, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.003, 0.011, 0.001, 0.024, 0.005, 0.019, and 0.031, respectively). While IHC provided localization, WB offered greater precision. WB revealed that, compared to the lymphoma group, the LGBLEL group exhibited significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.012, 0.005, 0.009, 0.011, 0.008, and 0.003, respectively) and lower expression of CCR1 (p = 0.014). The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma.

Is Orbital Lobe of the Lacrimal Gland Dispensable? Tear Volume, Ocular Surface, and MRI Volumetric Analysis.

To investigate the effects of lacrimal gland reduction surgeries on the tear volume and ocular surface. This is a cohort study of patients post 2 lacrimal gland reduction surgeries: partial orbital lobe dacryoadenectomy for refractory epiphora (4 patients, mean age: 31 ± 13.6 years, 3 males) and complete orbital lobe dacryoadenectomy for lacrimal gland pleomorphic adenoma (15 patients, mean age: 41 ± 12 years, 7 females). Changes in Schirmer I, ocular surface staining, symptomatology, and lacrimal gland volumetrics (MRI) were assessed before and after the surgical procedure. The median Schirmer value reduction following partial orbital lobe dacryoadenectomy was 5 mm at a mean follow-up of 18 ± 4.9 months. None of them developed dry eye disease or positive ocular staining. The gland volume was reduced by 45.9% to 53.5% in 3 patients and 13.3% in 1 patient. The epiphora improved moderately in 93% of patients. Of 15 patients with lacrimal gland pleomorphic adenoma excision, the median reduction in Schirmer I was 4 mm at a mean follow-up of 12.8 months. Partial or complete removal of the orbital lobe of the lacrimal gland does not induce dry eye disease in otherwise healthy individuals. However, gland volume does not recover following partial reduction, and it seems unlikely that the lacrimal gland regenerates following partial removal.

Central Retinal Artery Occlusion Following Intralesional Triamcinolone Injection for IgG4-related Orbital Disease.

The risk of blindness associated with periocular and facial injections is well documented. Previous cases describing vision loss following a recent periocular or facial injection have emphasized the importance of facial "danger zones." To date, the literature suggests that nearly half of all cases of central retinal artery occlusion in the setting of a recent periocular or facial injection involve an injection in or around the nose. Here, the authors report the second known case of central retinal artery occlusion following a triamcinolone injection to the lacrimal gland. A 30-year-old female with a diagnosis of IgG4-related disease underwent lacrimal gland debulking with an intralesional steroid injection. She noted OD vision loss immediately after surgery, with posterior segment examination demonstrating retinal whitening with a cherry-red spot and intra-arterial yellow-white plaques. This case serves as a reminder to clinicians regarding the risk of iatrogenic embolism following triamcinolone injections around the face with special attention drawn to the lacrimal gland.

A Review of the Tear Film Biomarkers Used to Diagnose Sjogren's Syndrome.

This literature review looks at Sjogren's Syndrome (SS), a chronic autoimmune disorder affecting exocrine glands, particularly the lacrimal and salivary glands. SS manifests as ocular and oral dryness, with severe complications like visual dysfunction and corneal perforation, as well as systemic implications, such as interstitial lung disease and lymphoma. This review explores the use of tear film biomarkers to diagnose SS, emphasizing the significance of their identification in aiding clinical diagnosis and differentiation from other diseases. This study identified and analyzed 15 papers, encompassing 1142 patients and employing various tear sample collection methods. Tear biomarkers were categorized by function and explored in-depth. Categories include (1) antimicrobials, antivirals, and antifungals; (2) components of immune regulation; (3) components that regulate metabolic processes; and (4) inflammatory markers. Noteworthy findings include the potential diagnostic values of tear lysozyme, lactoferrin, dinucleoside polyphosphates, cathepsin, defensin, antibodies, epidermal fatty acid-binding protein, HLA-DR, ADAM10, aquaporin 5, and various miRNAs and mRNAs. Overall, our understanding of SS tear film composition is enhanced, providing valuable insights into the pathogenesis of SS and offering a foundation for future diagnostic and therapeutic advancements in autoimmune conditions affecting the ocular surface.

The involvement of aquaporin 5 in the inflammatory response of primary Sjogren's syndrome dry eye: potential therapeutic targets exploration.

Sjogren's syndrome (SS) is a chronic autoimmune disease. Mainly due to the infiltration of lymphoplasmic cells into the exocrine glands, especially the salivary glands and lacrimal glands, resulting in reduced tear and saliva secretion. Reduced tear flow can trigger Sjogren's syndrome dry eye (SSDE). Although the pathophysiology of SSDE xerosis remains incompletely understood, recent advances have identified aquaporin-5 (AQP5) as a critical factor in dysregulation of the exocrine gland and epithelium, influencing the clinical presentation of SSDE through modulation of inflammatory microenvironment and tear secretion processes. This review aims to explore AQP5 regulatory mechanisms in SSDE and analyze its potential as a therapeutic target, providing new directions for SSDE treatment.