MSC-Derived Small Extracellular Vesicles Attenuate Autoimmune Dacryoadenitis by Promoting M2 Macrophage Polarization and Inducing Tregs via miR-100-5p.

Background: Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied. Methods: Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores. Quantitative real-time PCR (Q-PCR), western blot and flow cytometry were performed to evaluate the immunomodulatory effects of hUC-MSC-sEVs on macrophages and T regulatory cells (Tregs) both in vivo and in vitro, and the in vitro T cell proliferation was detected by Bromodeoxyuridine (BrdU) assay. In addition, high expression of miR-100-5p in hUC-MSC-sEVs was identified by Q-PCR, and the functional role of sEVs-miR-100-5p on macrophages was explored by a series of co-culture experiments using sEVs derived from hUC-MSCs transfected with miR-100-5p inhibitor. Results: We firstly demonstrated that hUC-MSC-sEVs had the preventive and therapeutical effects on rabbit autoimmune dacryoadenitis, an animal model of Sjögren's syndrome (SS) dry eye. Further investigation revealed that hUC-MSC-sEVs administration effectively elicited macrophages into an anti-inflammatory M2 phenotype and elevated the proportion of Tregs both in vivo and in vitro, which contributed to reduced inflammation and improved tissue damage. Importantly, hUC-MSC-sEVs-educated macrophages with M2-like phenotype exhibited strong capacity to inhibit CD4+ T cell proliferation and promote Treg generation in vitro. Mechanistically, miR-100-5p was highly enriched in hUC-MSC-sEVs, and knockdown of miR-100-5p in hUC-MSC-sEVs partially blunted the promotion of hUC-MSC-sEVs on M2 macrophage polarization and even attenuated the effect of hUC-MSC-sEVs-educated macrophages on T cell suppression and Treg expansion. Conclusion: Our data indicated that hUC-MSC-sEVs alleviated autoimmune dacryoadenitis by promoting M2 macrophage polarization and Treg generation possibly through shuttling miR-100-5p. This study sheds new light on the application of MSC-sEVs as a promising therapeutic method for SS dry eye.

Bacterial dacryoadenitis: clinical features, microbiology, and management of 45 cases, with a recent uptick in incidence.

PURPOSE: To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution. METHODS: This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission. RESULTS: Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1 years. Presenting symptoms included eyelid edema (100%), extraocular motility restriction (53.3%), and purulent discharge (75.5%). Based on computed tomography or magnetic resonance imaging, 9 (20.5%) patients presented with definite abscess and 15 (34%) presented with a phlegmon or early abscess. Eleven patients (24.4%) required surgical drainage. Twenty patients (44.4%) required admission, for an average stay of 4 days (range 2-8 days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. Presence of an early abscess or phlegmon correlated with need for drainage (p < 0.01). Extraocular motility restriction correlated with need for drainage (p = 0.02) and admission (p = 0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2%. In 2019, our institution had 17 cases (incidence 36.2%) of bacterial dacryoadenitis. CONCLUSIONS: Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.

Lacrimal Fossa Bony Changes in Chronic Primary Acquired Nasolacrimal Duct Obstruction and Acute Dacryocystitis.

PURPOSE: This study aims to assess the bony lacrimal fossa changes in chronic cases of primary acquired nasolacrimal duct obstruction versus acute dacryocystitis. METHODS: A prospective study was performed on 25 bony lacrimal fossae of 25 eyes of 15 patients who underwent endoscopic dacryocystorhinostomy at a tertiary care Dacryology service over a period of 6 months. Ten patients with chronic PANDO (> 1 year) with bilateral involvement and five patients of unilateral acute dacryocystitis were recruited in the study. None of the patients had a history of trauma or previous surgeries or nasal disease in the past. The bone samples from the frontal process of the maxilla and the lacrimal bone were obtained during the osteotomy and subjected to routine histopathological examination. Special stains used were von Kossa, Masson trichrome, periodic acid Schiff, and Alcian blue. Immunohistochemistry was performed using CD68 antibodies. Patient demographics, clinical presentation, duration of the disease, and bony changes were analyzed in different patient subsets. RESULTS: The mean disease duration in the chronic PANDO subset was 3.1 years, whereas acute dacryocystitis was 6.8 days. There was no correlation between the bony changes and the laterality in the chronic subset. Periosteal thickness and fibrosis were universal in the chronic group but not in the acute dacryocystitis. There were also differences in the number of osteocytes per sq mm, osteoblast, osteoclast, bony remodeling, bony canals structure, and intrastromal fibrosis between the subsets. These changes within the chronic group increased with the duration of the disease. Interestingly, there was no evidence of any bony inflammation across the subsets in all the samples studied. CONCLUSION: Characteristic bony changes can be demonstrated in patients with chronic PANDO but not in acute dacryocystitis. The lack of bony inflammatory infiltrates may provide clues in understanding the peri-sac disease pathogenesis in acute dacryocystitis.

Presentation, Diagnostic Evaluation, Management, and Rates of Serious Bacterial Infection in Infants With Acute Dacryocystitis Presenting to the Emergency Department.

BACKGROUND: Dacryocystitis is considered benign, yet infants represent a population at risk of complications. The presentation, management, and rates of serious bacterial infection in infants with dacryocystitis have not been described. METHODS: We conducted a retrospective study of infants (12 months or younger) presenting to a single urban tertiary care pediatric emergency department between January 1995 and March 2014 with concern for dacryocystitis. Exclusion criteria included immune compromise or craniofacial anomalies. Cases were identified using text search software, followed by manual chart review. RESULTS: We identified 333 subjects, and median age was 38 days (interquartile range, 12; 106). Fifty-three percent were female. Most were afebrile (81%, T < 38°C) at triage while 6% had fever of ≥39°C. Two of 135 blood cultures sent were positive (both Streptococcus pneumoniae). Lumbar punctures were performed on 40 patients (12%), and no cerebrospinal fluid (CSF) cultures were positive. Eye cultures were positive in 47% (N = 58) of infants cultured (N = 123); the most common pathogens were Haemophilus species (N = 17), Staphylococcus aureus (N = 13), Gram-negative rods (N = 7), and Moraxella species (N = 4). Imaging was obtained in 11 subjects (3.3%) with 3 demonstrating cellulitis and 1 a hemangioma. Ophthalmology was consulted for 21%, and an intervention/probe performed in 6%. Topical antibiotics were used in 147 subjects (44%), oral antibiotics in 100 (33%), and parenteral antibiotics in 87 (26%). CONCLUSION: Infants with dacryocystitis have a variable presentation and management ranges from observation to aggressive management. The rates of serious bacterial infection were low in this sample and not associated with any presenting risk factors.

Acute dacryocystitis with giant lacrimal abscess: a case report.

BACKGROUND: We report a case of a 4-year-old girl with acute dacryocystitis complicated with giant lacrimal abscess who underwent open dacryocystectomy as resolutive surgery. CASE PRESENTATION: A 4-year-old previously healthy girl presented to the emergency department with a voluminous and erythematous, fluctuant warm mass localized inferiorly to the medial canthus of the right eye. She had a 2-week history of right inferior eyelid oedema and hyperemia, treated firstly with dexamethasone and netilmicin by eye drops, and then with per oral amoxicillin clavulanate. Ultrasound examination showed a well-circumscribed round lesion filled by anechoic fluid with punctate echoes, confirming a diagnosis of acute dacryocystitis complicated by lacrimal abscess. Parents refused a head CT. Systemic antibiotic treatment was started and, on 5th day from admission, open dacryocystectomy was performed with good esthetical result. CONCLUSIONS: Pediatric acute dacryocystitis is a potentially serious condition, which must be treated with intravenous antibiotic therapy followed by surgery tailored to the clinical history. Even if probing and dacryocystorhinostomy are the most used surgery in adults and children, open dacryocystectomy is a safe and successful option, mainly in severe cases where imaging studies are not available.

A 6-Week, Prospective, Randomized, Single-Masked Study of Lifitegrast Ophthalmic Solution 5% Versus Thermal Pulsation Procedure for Treatment of Inflammatory Meibomian Gland Dysfunction.

PURPOSE: Meibomian gland dysfunction (MGD) is present in most cases of dry eye disease. MGD involves both inflammatory and obstructive etiologies. We compared efficacy and safety of treatment to reduce inflammation (lifitegrast) versus obstruction [thermal pulsation procedure (TPP)] in patients with inflammatory MGD over 42 days. METHODS: This was a single-center, 6-week, prospective, randomized, single-masked study of adults with inflammatory MGD, defined as having all of the following: burning, stinging, dryness; thickened secretions or occlusion of glands; eyelid redness; and elevated matrix metalloproteinase-9. Patients received lifitegrast ophthalmic solution 5% twice daily for 42 days or one TPP treatment at day 0. Seven symptoms and 8 objective measures of dry eye disease were assessed. RESULTS: Overall, 40 of 50 randomized patients (80%) were women with mean (SD) age 65.8 (8.9) years. Lifitegrast-treated (n = 25) versus TPP-treated (n = 25) patients had greater improvement from baseline to day 42 in eye dryness [mean (SD) change from baseline: -1.05 (0.79), lifitegrast; -0.48 (0.96), TPP; P = 0.0340], corneal staining [-0.55 (0.80), lifitegrast; 0.12 (1.09), TPP; P = 0.0230], and eyelid redness [-0.77 (0.43), lifitegrast; -0.38 (0.58), TPP; P = 0.0115]; trend favored lifitegrast for best corrected visual acuity and gland patency. Unexpectedly, TPP treatment did not improve lipid layer thickness or gland patency compared with lifitegrast. No adverse events were reported. CONCLUSIONS: Although MGD is often considered a disease of gland obstruction, these findings demonstrate antiinflammatory treatment with lifitegrast significantly improved patient symptoms and signs compared with treatment for obstruction (TPP). Lifitegrast should be included in treatment for inflammatory MGD.

Bilateral dacryocystitis complicated by unilateral retrobulbar abscess in a five-week-old infant.

Retrobulbar orbital abscess in children is a rare condition, and diagnosis and management can be challenging. We report the case of a 5-week-old male infant with retrobulbar orbital abscess secondary to acute dacryocystitis developed from a dacryocystocele. The patient presented with respiratory difficulty, sepsis and progressive clinical findings suggestive of post-septal cellulitis. He was successfully treated with endonasal incision of subturbinate dacryocystoceles followed by probing of the lacrimal ducts. Congenital dacryocystocele must be considered a differential diagnosis in infants with respiratory difficulty and may develop into a vision- and life-threatening condition requiring immediate intervention.

Ocular Surface Disease of Rabbits.

Rabbits have become a popular house pet that is encountered with increasing frequency in small animal veterinary practice. The unique anatomy of the rabbit predisposes them to developing surface ocular problems including the development of dacryocystitis, as well as conjunctivitis and keratitis. This article endeavors to give an updated outline of the various conditions affecting the rabbit ocular surface, with emphasis on diagnosis and treatment.

Primary tubercular dacryocystitis - a case report and review of 18 cases from the literature.

Tuberculosis is an airborne communicable disease primarily affecting lungs. Primary tuberculosis of the lacrimal sac is very rare. A 15-year-old girl presented with bilateral epiphora for 8 months. Examination revealed bilateral nasolacrimal duct obstruction. During dacryocystorhinostomy, bone over lacrimal sac was found partially eroded. Lacrimal sac was found filled with caseous white material. Biopsy from the lacrimal sac revealed tubercular granulomas. Patient improved after anti-tubercular therapy. Abbreviations: PCR: polymerase chain reaction; NAAT: nucleic acid amplification test.

Mesenchymal stem cells for treating autoimmune dacryoadenitis.

Autoimmune dacryoadenitis, such as Sjögren syndrome, comprises multifactorial and complex diseases. Inflammation of the lacrimal gland plays a key role in the pathogenesis of diseases. Unfortunately, current treatment strategies, including artificial tears, anti-inflammatory drugs, punctual occlusion, and immunosuppressive drugs, are only palliative, and long-term administration of these strategies is associated with adverse effects that limit their utility. Hence, an effective and safe treatment for autoimmune dacryoadenitis is urgently needed. Mesenchymal stem cells (MSCs) have emerged as a promising tool for treating autoimmune dacryoadenitis, owing to their immunosuppressive properties, tissue repair functions, and powerful differentiation capabilities. A large number of studies have focused on the effect of MSCs on autoimmune diseases, such as autoimmune uveitis, inflammatory bowel disease, and collagen-induced arthritis, but few studies have, to date, unequivocally established the efficacy of MSCs for treating autoimmune dacryoadenitis. In this review, we discuss recent advances in MSC treatment for autoimmune dacryoadenitis.

Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a Rabbit Model of Induced Autoimmune Dacryoadenitis.

PURPOSE: To investigate the immunoregulatory roles of adipose-derived mesenchymal stem cells (ADSCs) in autoimmune dacryoadenitis. METHODS: Rabbits were treated with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after injection of activated peripheral blood lymphocytes, and clinical scores were determined by assessing tear production, break-up time, and fluorescein and hematoxylin and eosin staining. Inflammatory response was determined by measuring the expression of different mediators of inflammation in the lacrimal glands. The Th1/Th17-mediated autoreactive responses were evaluated by determining the proliferative response and the expression of cytokine genes and the lineage-determining transcription factors. The frequency of regulatory T cells (Tregs) was also examined. RESULTS: The ADSC-treated rabbits showed decreased autoimmune responses, and the secretory function of their lacrimal gland was restored significantly. Treatment with ADSCs downregulated the Th1 and Th17 responses but enhanced Tregs function. In addition, ADSC treatment noticeably suppressed the expression of matrix metalloproteinase (MMP)-9, MPP-2, IL-1ß, and IL-6, whereas it enhanced the expression of the anti-inflammatory cytokine IL-10. CONCLUSIONS: Our results demonstrated that ADSC administration efficiently ameliorates autoimmune dacryoadenitis mainly via modulating Th1/Th17 responses.

Clinical and microbiologic features of dacryocystitis-related orbital cellulitis.

Dacryocystitis-related orbital cellulitis is a relatively rare condition, and large case series of this clinical entity have been reported. This study was undertaken to identify a larger cohort of patients with this ailment, with the intent of defining its clinical and microbiologic features. Case logs from four institutions were reviewed to identify patients that suffered from dacryocystitis-related orbital cellulitis. A retrospective chart review was then performed to identify clinical features, management strategies, microbiologic features, and outcomes. A dedicated statistical software package was utilized to identify correlations between these variables. 13 patients (7 females, 6 males; mean age = 57.2 years, range = 7-89 years) were identified. One patient carried a diagnosis of immunosuppressive disease. All patients underwent emergent surgical drainage and received intravenous antibiotics. Primary acquired nasolacrimal duct obstruction was found to be the underlying etiology in nine cases (69.2%), whereas four patients suffered from specific causes of their obstructions. An average of 1.07 organisms/patient (standard deviation = 0.49 organisms/patient) were recovered from microbiologic cultures, and Gram-positive bacteria represented the majority of cultured organisms. All patients experienced either stable or improved vision upon discharge. The relationships between a specific etiology and the possibility of vision loss or the number of organisms cultured, between the number of organisms cultured and vision loss, and immunosuppression and vision loss or the number of organisms cultured were all not statistically significant (p > 0.05). Dacryocystitis-related orbital cellulitis most commonly occurs in adult patients who do not carry immunosuppressive diagnoses and suffer from primary obstructions. Multiple microbiologic species may cause this problem, although Gram-positive organisms are most common. With appropriate management, stable or improved vision can be achieved.

Dacriocistorrinostomía externa: resultados en un año de experiencia en Villa Clara / External dacryocystorhinostomy: outcomes achieved in one-year experience in Villa Clara province

Objetivo: describir los resultados de la cirugía dacriocistorrinostomía externa en un año. Métodos: se realizó un estudio observacional, descriptivo longitudinal prospectivo en 25 pacientes, 28 ojos. Se consideraron las variables sexo, color de piel, edad, lado afectado, etiología, complicaciones y resultados de la cirugía.Resultados: hubo 7 pacientes masculinos y 18 femeninos; de ellos, 16 blancos y 9 no blancos con una diferencia estadísticamente significativa (p= 0,043). La edad promedio fue de 69 ± 11 años. En 13 pacientes (52,0 por ciento) se afectó el lado izquierdo y en el 68,0 por ciento la etiología fue involutiva con significación estadística (p= 0,0003). El sangramiento transoperatorio se presentó como complicación en el 24,0 por ciento de los pacientes. El 92,0 por ciento refirió mejoría de la sintomatología después de operados. Según el criterio del cirujano, la mejoría objetiva se obtuvo en el 88,0 por ciento de los casos. La dacriocistorrinostomía externa fue más frecuente en mujeres blancas encontradas entre su sexta y séptima década de vida. El lado izquierdo fue el más afectado con predominio de la etiología involutiva. Las complicaciones fueron escasas; dentro de ellas predominó el sangramiento transoperatorio. Conclusiones: la mayoría de los pacientes sintieron mejoría después de la cirugía; el criterio del cirujano estuvo a favor de los resultados positivos en la cirugía dacriocistorrinostomía externa(AU)

Objective: to describe the results of external dacryocystorhinostomy surgery in one year. Methods: a prospective, longitudinal descriptive and observational study was conducted in 28 patients from 25 patients. The study variables were gender, race, age, affected side, etiology, complications and surgery outcomes. Results: there were 7 male and 18 female patients, 16 Caucasians and 9 non-Caucasians with statistically significant difference (p= 0,043). The mean age was 69 ± 11 years. The obstruction involved the left side in 13 patients (52 percent) and involution was the main etiology in 68 percent with statistical significance (p= 0,0003). Perioperative bleeding was the main complication (24 percent). In the group, 92 percent said the symptoms had reduced after surgery, and according to the surgeon, objective improvement was attained in 88 percent of cases.Conclusion: external dacryocystorhinostomy was more frequent in Caucasian women aged 60 to 70 years. The left side was the most affected, with prevailing involution etiology. There were minimum complications, being perioperative bleeding predominant. Most of the patients felt better after surgery and the surgeon´s criteria were in favor of the positive results of this surgery(AU)

Dacriocistorrinostomía externa: resultados en un año de experiencia en Villa / External dacryocystorhinostomy: outcomes achieved in one-year experience in Villa Clara province

Objetivo: describir los resultados de la cirugía dacriocistorrinostomía externa en un año. Métodos: se realizó un estudio observacional, descriptivo longitudinal prospectivo en 25 pacientes, 28 ojos. Se consideraron las variables sexo, color de piel, edad, lado afectado, etiología, complicaciones y resultados de la cirugía. Resultados: hubo 7 pacientes masculinos y 18 femeninos; de ellos, 16 blancos y 9 no blancos con una diferencia estadísticamente significativa (p= 0,043). La edad promedio fue de 69 ± 11 años. En 13 pacientes (52,0 por ciento) se afectó el lado izquierdo y en el 68,0 por ciento la etiología fue involutiva con significación estadística (p= 0,0003). El sangramiento transoperatorio se presentó como complicación en el 24,0 por ciento de los pacientes. El 92,0 por ciento refirió mejoría de la sintomatología después de operados. Según el criterio del cirujano, la mejoría objetiva se obtuvo en el 88,0 por ciento de los casos. La dacriocistorrinostomía externa fue más frecuente en mujeres blancas encontradas entre su sexta y séptima década de vida. El lado izquierdo fue el más afectado con predominio de la etiología involutiva. Las complicaciones fueron escasas; dentro de ellas predominó el sangramiento transoperatorio. Conclusiones: la mayoría de los pacientes sintieron mejoría después de la cirugía; el criterio del cirujano estuvo a favor de los resultados positivos en la cirugía dacriocistorrinostomía externa(AU)

Objective: to describe the results of external dacryocystorhinostomy surgery in one year. Methods: a prospective, longitudinal descriptive and observational study was conducted in 28 patients from 25 patients. The study variables were gender, race, age, affected side, etiology, complications and surgery outcomes. Results: there were 7 male and 18 female patients, 16 Caucasians and 9 non-Caucasians with statistically significant difference (p= 0,043). The mean age was 69 ± 11 years. The obstruction involved the left side in 13 patients (52 percent) and involution was the main etiology in 68 percent with statistical significance (p= 0,0003). Perioperative bleeding was the main complication (24 percent). In the group, 92 percent said the symptoms had reduced after surgery, and according to the surgeon, objective improvement was attained in 88 percent of cases. Conclusion: external dacryocystorhinostomy was more frequent in Caucasian women aged 60 to 70 years. The left side was the most affected, with prevailing involution etiology. There were minimum complications, being perioperative bleeding predominant. Most of the patients felt better after surgery and the surgeon´s criteria were in favor of the positive results of this surgery(AU)