Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype.

Mesenchymal stem cells (MSCs) exhibit beneficial effects on autoimmune dacryoadenitis. However, the underlying mechanisms are not fully understood. In this study, we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on rabbit autoimmune dacryoadenitis, an animal model of Sjögren's syndrome (SS) dry eye, and explored whether the effects of MSCs were related to their modulation on macrophage polarization. We have showed that systemic infusion of hUC-MSCs after disease onset efficiently diminished the chronic inflammation in diseased LGs and improved the clinical symptoms. Further analysis revealed that hUC-MSC treatment significantly inhibited the expression of pro-inflammatory M1 macrophage markers iNOS, TNF-α and IL-6, and promoted the expression of anti-inflammatory M2 macrophage markers Arg1, CD206, IL-10, IL-4 and TGF-ß in LGs. Mechanistically, hUC-MSCs activated AKT pathway in macrophages, resulting in upregulation of M2-associated molecule Arg1, which was partly abolished by PI3K inhibitor, LY294002. Together, our data indicated that hUC-MSCs can skew macrophages into an M2 phenotype via affecting AKT pathway. These data may provide a new insight into the mechanisms of hUC-MSCs in the therapy of SS dry eye.

Long-term outcomes of cruciate marsupialization of intra-nasal cysts in patients with congenital dacryocele.

OBJECTIVES: To evaluate the long-term outcomes of cruciate marsupialization of intranasal cysts associated with congenital dacryocele. METHODS: This is a retrospective review of 15 patients of dacryoceles with intranasal cysts who underwent cruciate marsupialization of the medial wall of the cyst. Post-operative follow up for a minimum of 9 months was an inclusion criterion for analysis. Data analyzed include demographics, clinical presentations, previous interventions, associated systemic abnormalities, clinical course following marsupialization and recurrences. Primary outcome measures were resolution of the dacryocele and symptomatic relief from epiphora. RESULTS: The mean age at presentation was 1.6 months with a female preponderance (60%). History of prematurity (pre-term) was noted in 20% (3/15). Swelling in the lacrimal sac area (dacryocele) was the universal presentation. Five patients (33.3%) had a prior conservative treatment. Four patients (26.6%) had respiratory distress with feeding. Acute dacryocystitis was noted in 26.6% (4/15). At a mean follow up of 19.1 months, successful outcomes were achieved in 86.6%. CONCLUSION: Cruciate marsupialization of intranasal cysts achieves good results in patients with congenital dacryocele, which are maintained over a long period of time. Early diagnosis and management may prevent acute dacryocystitis in these patients.

[Tumors of the lacrimal drainage system]. / Tumoren der ableitenden Tränenwege.

BACKGROUND: The prevalence of tumors affecting the lacrimal drainage system is low, thus generating a risk of late diagnosis and treatment in clinical routine. However, these tumors can be potentially life-threatening, which emphasizes the relevance of early diagnosis and treatment. OBJECTIVE: This review focuses on the symptoms, incidence, management, and prognosis of the different tumor entities affecting the lacrimal drainage system. METHODS: The study provides a PubMed-based literature review and presents own clinical results. RESULTS: Alongside detailed medical history taking and comprehensive clinical examination, precise inspection during external dacryocystography is important for diagnosis of tumors affecting the lacrimal drainage system. There is a wide spectrum of tumor entities located in the lacrimal drainage system. The tumors are classified into three groups: primary epithelial, primary nonepithelial, and inflammatory lesions. The most common primary epithelial tumors include papilloma, squamous cell carcinoma, and transitional cell carcinoma. The most common nonepithelial tumors include fibrous histiocytoma, malignant lymphoma, and malignant melanoma; while the most common inflammatory lesions comprise sarcoidosis, Wegener granulomatosis, and pyogenic granuloma. Treatment depends on the entity and stage of the tumor. In the case of malignancy, a multimodal and interdisciplinary approach is usually indicated. CONCLUSION: Differential diagnostic signs in favor of a malignancy include a long medical history, predisposing conditions in the patient's history, a mass above the medial canthal ligament, teleangiectasis above the mass, and serosanguinous secretion.

EFFECT OF INTRAOPERATIVE MITOMYCIN-C APPLICATION IN OUTCOME OF EXTERNAL DACRYOCYSTORHINOSTOMY.

BACKGROUND: Patients develop postoperative fibrosis at the site of operation after dacryocystorhinostomy (DCR) which results in impairment of the osteum patency. This quasi-experimental study was undertaken to determine the role of intraoperative Mitomycin C (MMC) application in maintaining postoperative patency of the osteum. METHODOLOGY: The present study was conducted at the Eye department of Ayub Medical College, Abbottabad on patients in whom routine DCR was indicated. Subjects were divided into mitomycin C (Test) and non mitomycin C (Control) groups. In test group, Mitomycin C was applied to the anastomosed flaps and osteotomy site for 30 minutes. Postoperative patients were followed for up to 6 months and outcome of patency was documented. RESULTS: A.total of 73 patients were included, divided into test (30) and control (43) groups. An overall success rate of 86.3% was obtained for patent ostia; this was based on 96.67% success in test group compared to 79.1% in the control group (p=0.031). CONCLUSION: Intraoperative application of Mitomycin-C significantly improves the success rate in external dacryocystorhinostomy.

Clinical outcomes of dacryocystorhinostomy with or without intraoperative use of mitomycin C: a systematic review and meta-analysis.

PURPOSE: To examine the possible benefit of intraoperative use of mitomycin C (MMC) application in dacryocystorhinostomy (DCR) and to assess its potential risk. METHODS: Systematic review and meta-analysis of randomized-controlled trials (RCTs). A comprehensive literature search was performed according to a protocol set in advance. The participants included 811 patients of which 820 eyes were sampled for 14 RCTs. Only pertinent RCTs were identified and included in this meta-analysis. The primary efficacy measure was "patency of irrigation" at follow-up end point. The subjective outcome of "symptom relief" was also extracted as a secondary efficacy measure. For each study, relative risk was extracted. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: RevMan version 5.0 software was used for statistical analysis. In the primary efficacy measure, the use of MMC can significantly increase the rate of "patency of irrigation" [risk ratio (RR), 1.10; 95% confidence interval (CI), 1.04-1.17; P=0.0006]; the outcome of "symptom relief" was also affected by the use of MMC (RR, 1.15; 95% CI, 1.05-1.26; P=0.003). Sensitivity analysis suggested that the result was comparatively reliable. CONCLUSION: Intraoperative use of MMC can bring about a positive effect to the outcomes of "patency of irrigation" and "symptom relief," which increases the success rate of DCR surgery.

[Recurrent canaliculitis in a 22-year-old patient]. / Rezidivierende Canaliculitis bei einem 22-Jährigen.

A 22-year-old patient presented with persistent epiphora over a period of about 7 months. The clinical examination revealed a canalicular swelling in both lacrimal ducts, which postoperatively transpired to be an exophytic tumor. The histopathology result of the excised tumor showed an epithelial lesion, a partially inverted papilloma without malignancy. For tumors arising from lachrimal ducts the first-line therapy is complete tumor resection.

[Nasolacrimal duct disorders in children. Part I. Anatomy, physiology and clinical signs]. / Schorzenia dróg lzowych u dzieci. Czesc I. Anatomia, fizjologia i objawy.

Congenital nasolacrimal duct obstruction (CLDO) is considered as common and onerous disorder present at infancy. Over 5% of infants have CLDO affecting one or both eyes. The symptoms of CLDO appear shortly after birth or during the first weeks of life. The main symptoms are: excessive and persistent watering, ropy mucous discharge in the conjunctival sac. In conservative treatment a lacrimal sac massage is proposed, though it is not always successful. Topical antibiotics are reserved only if secondary conjunctivitis occurs. Fortunately, most cases resolve spontaneously. However, sometimes nasolacrimal duct probing performed under local or general anesthesia is necessary.

[Nasolacrimal duct disorders in children. Part II. Treatment]. / Schorzenia dróg lzowych u dzieci. Czesc II. Metody leczenia.

Congenital nasolacrimal duct obstruction (CLDO) is considered as common and onerous disorder present at infancy. Over 5% of infants have CLDO affecting one or both eyes. The symptoms of CLDO appear shortly after birth or during the first weeks of life. The main symptoms are: epiphora, ropy, mucous discharge in the conjunctival sac. In conservative treatment a lacrimal sac massage is proposed, though it is not always successful. Topical antibiotics are reserved only if secondary conjunctivitis occurs. Fortunately, most cases resolve spontaneously. However, sometimes nasolacrimal duct probing performed under local or general anesthesia is necessary. Prognosis for probing decreases with the increasing number of probings and the age of the patient. In children, who have failed nasolacrimal duct probing, intubation or balloon catheter dilatation of the nasolacrimal system with or without silicone tubing should be considered. In the case of the upper sac obstructions one can use laser endoscopic dacryocystorhynostomy. If it is still not amenable to opening a endonasal endoscopic dacryocystorhinostomy (EESC-DCR), or traditional external dacryocysto-rhinostomy (EXT-DCR), should be performed.

[To the prevention of recurrent dacryocystitis after surgical treatment].

The efficacy of collagenase KK was evaluated in the treatment of 121 patients with lacrimal duct diseases. Collagenase KK used to prevent recurrent lacrimal duct disease contributed to a significant relief of an inflammatory process (by an average of 2.04+/-0.2 days as rapidly as in the controls), recovery of nasal lacrimation, shorter treatment (by an average of 1.8+/-0.11 bed/days), a reduction in the number of complications (by 2.1 times). The findings enable the authors to recommend the agent for wide clinical application in combination with other treatments.

The Wistar Bonn Kobori rat, a unique animal model for autoimmune pancreatitis with extrapancreatic exocrinopathy.

The male Wistar Bonn/Kobori (WBN/Kob) rat is known to be a unique animal model for chronic pancreatitis with widely distributed fibrosis and degeneration of parenchyma because of the infiltration of lymphocytes. In this report, we show that female (but not male) rats develop dacryoadenitis at 3 months of age, and that both male and female WBN/Kob rats develop sialoadenitis, thyroiditis, sclerotic cholangitis and tubulointerstitial nephritis over 18 months of age. The infiltration of CD8+ cells and the deposits of tissue-specific IgG2b were observed in the injured pancreas and lachrymal glands. Furthermore, the number of regulatory T cells (defined as CD4+ Forkhead box P3+ cells) decreased in the periphery of both male and female WBN/Kob rats, suggesting that the onset of these diseases is attributable, at least, to the failure in the maintenance of peripheral immune tolerance. These features show clearly that WBN/Kob rats are a useful animal model for autoimmune pancreatitis and Sjøgren-like syndrome or multi-focal fibrosclerosis in humans. We also show that these autoimmune diseases can be prevented by a newly devised strategy of bone marrow transplantation (BMT) in which bone marrow cells are injected directly into the bone marrow cavity: intrabone marrow-BMT.

[Evaluation of therapy outcome in congenital nasolacrimal duct obstruction in own material]. / Ocena leczenia wrodzonej niedroznosci dróg lzowych w materiale wlasnym.

UNLABELLED: The inborn nasolacrimal duct obstruction is common ocular disease in new-borns and infants. There are still doubts concerning the timing of the operating procedure. Probing of the lacrimal ducts is the therapeutic method for this condition. PURPOSE: To evaluate the therapy outcome in congenital nasolacrimal duct obstruction in authors' own material. MATERIAL AND METHODS: In retrospective study of 3950 medical records of children from our Outpatient's Clinic, we distinguished 192 children with nasolacrimal duct obstruction. Then, we evaluated the outcome of implemented treatment in correlation with their age and timing of the nasolacrimal duct probing. RESULTS: All children with nasolacrimal duct obstruction had mucopurulent discharge in the lacrimal sac and lacrimation. After the conventional treatment, the disease resolved in 23% of our group, whereas, in the rest of the patients probing of the nasolacrimal duct was implemented. The probing was successful in all children, but it was necessary to repeat the procedure twice in 13 children and three times in 5 children. The success rate of single probing was as follows: 91% in the group of children 1 - 3 months old, 83% in both groups: 3 - 6 and 6 - 12 months old and 71% in the oldest group of children - above 1 year of age. CONCLUSIONS: In majority of children the nasolacrimal duct obstruction did not resolve spontaneously. Early probing within first few months of child's life increased the success rate of this procedure.

[Excessive tearing in infants and young children. Questions? Answers]. / Le larmoiement du petit enfant. Questions? Réponses...

Tearing in infants and young children is a subject of controversy. A logical succession of questions and answers is helpful in developing a consensual attitude.

Oral and topical antibiotic therapy of complete, primary acquired nasolacrimal duct obstruction in adults.

PURPOSE: To determine whether patients with complete, acquired nasolacrimal duct obstruction may be treated with broad spectrum oral antibiotics and office lacrimal irrigation. METHODS: In a retrospective review, patients with complete, primary acquired nasolacrimal duct obstruction (NLDO) were divided by predominant symptoms and signs into two main groups: (a) those with tearing and/or mucous discharge and (b) those with previous acute dacryocystitis and/or lacrimal sac mucocele. All patients received a therapeutic trial of oral and topical antibiotics followed by lacrimal irrigation. RESULTS: Five of 55 patients with tearing and/or mucous discharge showed significant improvement after treatment with a mean follow-up of 16.5 months. A sixth patient with mucous and tearing had resolution of the mucous discharge but persistent tearing and blockage of the nasolacrimal system to irrigation. Two of 20 patients with lacrimal sac mucocele or history of acute dacryocystitis avoided surgery while 18 opted for early lacrimal surgical intervention. CONCLUSIONS: Conservative management of complete acquired NLDO consisting of oral and topical antibiotics and appropriately timed office lacrimal drainage system irrigation may be considered in selected patients.

Role of the ICAM-1/LFA-1 pathway during the development of autoimmune dacryoadenitis in an animal model for Sjögren's syndrome.

We have analyzed the role of cell adhesion molecules during the development of autoimmune dacryodenitis in an NFS/sld mouse model for primary Sjögren's syndrome. The expression of cell adhesion molecules was assessed by RT-PCR and immunohistochemistry. We detected an up-regulation of local cell adhesion molecule genes (ICAM-1, LFA-1, CD44 and Mel-14) in the course of autoimmune lacrimal gland diseases. Immunohistochemically, ICAM-1 was localized exclusively in the endothelial cells of variously sized blood vessels before the onset of disease, and LFA-1, CD44 and Mel-14, expressing infiltrating cells, were found within these lesions. When the therapeutic effects of blocking cell adhesion molecules in vivo were examined, antibodies to ICAM-1 in combination with anti-LFA-1 prevented the development of autoimmune lacrimal gland diseases in NFS/sld mice. These data suggest that in Sjögren's syndrome-like autoimmune dacryoadenitis in NFS/sld mutant mice, the ICAM-1/LFA-1 pathway may play a crucial role in the development and subsequent progression of T-cell-mediated autoimmunity in the lacrimal glands.