This study investigated the therapeutic effects of Yiguanjian on dry eye in rats and its mechanisms involving the T helper cell 17(Th17)/regulatory T cell(Treg) balance. The rat model of dry eye was established by administrating 0.2% benzalkonium chloride solution in eye drops. After successful modeling, the rats were treated with Yiguanjian for 4 consecutive weeks. The Schirmer test was carried out to assess the lacrimal gland function, corneal fluorescence staining to detect corneal injury, hematoxylin-eosin staining to observe corneal histopathology, enzyme-linked immunosorbent assay to measure serum levels of interleukin(IL)-6, IL-8, IL-17A, IL-21, and tumor necrosis factor-α(TNF-α), RT-qPCR to analyze mRNA levels of retinoic acid receptor-related orphan receptor gamma t(RORγt) and forkhead box protein p3(Foxp3) in the corneal tissue, immunofluorescence double staining to evaluate RORγt and Foxp3 expression in the lacrimal gland tissue, and Western blot to quantify the protein levels of signal transducer and activator of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), Janus kinase 2(Jak2), phosphorylated Jak2(p-Jak2), RORγt, and Foxp3 in the corneal tissue. The results demonstrated that Yiguanjian increased tear secretion(P<0.01), alleviated corneal damage and pathological changes, and lowered the serum levels of IL-6, IL-8, IL-17A, IL-21, and TNF-α(P<0.05) in model rats. Additionally, Yiguanjian decreased the ratio of RORγt to Foxp3 in the corneal and lacrimal gland tissue(P<0.01), downregulated the protein levels of STAT3, Jak2, and RORγt(P<0.05), upregulated the protein level of Foxp3(P<0.05), and inhibited phosphorylation of STAT3 and Jak2(P<0.01). These findings indicate that Yiguanjian ameliorates ocular surface dysfunction in dry eye rats by restoring Th17/Treg balance in the corneal and lacrimal gland tissue and suppressing systemic inflammatory cytokine release, thus mitigating ocular surface inflammation.
Animals ; Rats ; T-Lymphocytes, Regulatory/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Th17 Cells/immunology* ; Male ; Rats, Sprague-Dawley ; Dry Eye Syndromes/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/immunology* ; Lacrimal Apparatus/immunology* ; Humans ; STAT3 Transcription Factor/immunology*

Humans ; Lacrimal Apparatus ; Endoscopy ; Carcinoma ; Eyelids

Objective: To describe the clinicopathologic features and outcome of a patient with epithelial-myoepithelial carcinoma of the lacrimal gland who underwent modified lateral orbitotomy with en toto removal of the lesion and adjuvant radiotherapy. Methods: This is a case report. Results: A 31-year-old Filipino male seafarer presented with a 2-month history of an enlarging left superotemporal orbital mass and inferonasal displacement of the globe. Magnetic resonance imaging revealed a superotemporal extraconal mass within the lacrimal sac fossa with evidence of osseous infiltration of the superolateral orbital rim. Modified lateral orbitotomy was performed with en toto removal of the lesion and the clinically infiltrated adjacent lateral bony margin. Histopathologic diagnosis of epithelial-myoepithelial carcinoma of the lacrimal gland was made based on the classic and distinct biphasic morphology and was confirmed with immunohistochemistry studies (cytokeratin-7, S-100, and p63). Systemic surveillance using positron emission tomography and computed tomography scan with contrast revealed no evidence of regional or distant metastasis. Adjuvant radiotherapy of the orbital area was performed for increased local control. Twelve months postoperatively, the patient showed no evidence of tumor recurrence. Conclusion Epithelial-myoepithelial carcinoma of the lacrimal gland is a rare condition, and this is the first documented case from the Philippines. Accurate diagnosis is necessary for appropriate treatment. It should be included in the differential diagnosis of infiltrative lesions in the lacrimal gland fossa.
Lacrimal Apparatus

Objective: To describe the cytopuncture microbiopsy (CM) technique performed during transcanalicular endoscopic lacrimal duct recanalization (TELDR) in patients with primary acquired nasolacrimal duct obstruction (PANDO) as an alternative to open biopsy, the standard method used in collecting specimen. Methods: This is a noncomparative, interventional case series with histopathologic correlation. Patients diagnosed with complete PANDO who underwent TELDR with balloon dacryoplasty and silicone intubation with CM at University of Santo Tomas Hospital from October 2014 to January 2017 were included. Results: Twenty (20) tissue specimens from the lacrimal sac and nasolacrimal duct were obtained from 18 patients. There were 16 females and 2 males included in the study. Mean age was 57.5 years. All specimens revealed few clusters of benign epithelial cells with few degenerated mononuclear cells and lymphocytes, and singly scattered lymphocytes that are set in fibrinous background. Tissue cytology studies were negative for malignant cells. Conclusion CM is a minimally invasive procedure that offers an alternative to open biopsy technique that can be done routinely during TELDR.
Dacryocystorhinostomy ; Lacrimal Apparatus Diseases

Objective:To investigate the effectiveness of nasal endoscopic anterior lacrimal recess approach combined with temporary fenestration of the nasal septum in resecting recurrent nasal inverted papilloma. Methods:Patients with recurrent nasal inverted papilloma who underwent reoperation in our hospital during the past 2 years were included . The nasal septum may hinder full access to and effective treatment of the lesions at the anterior and medial wall of the maxillary sinus by endoscope, aspirator and surgical instrument in the narrow aperture of the prelacrimal recess, although these lesions could be observed by 70° nasal endoscope. Results:The nasal septum is temporarily opened on the basis of the prelacrimal recess approach, and the nasal endoscope and instrument was introduced through trans-septal window, so as to provide a better view of the operative field and the angular range of the instrument's movement. Conclusion:The recurrent nasal inverted papilloma could be successfully managed by re-endoscopic anterior lacrimal recess approach combined with temporary fenestration of the nasal septum, and no recurrence was observed during the 2-year follow-up. This surgical approach is recommended for the inverted papilla which originates from the anterior medial wall of the maxillary sinus, as the tumor can be removed completely using this surgical approach.
Humans ; Papilloma, Inverted/pathology* ; Endoscopy ; Maxillary Sinus/pathology* ; Lacrimal Apparatus/surgery* ; Treatment Outcome ; Retrospective Studies

PURPOSE: Congenital double puncta are usually unilateral, and the accessory punctum exists on the medial side in a slit configuration that is distinct from the shape of the normal punctum. We report a case of an unusual case of double lacrimal puncta which the lateral, rather than the medial, punctum was judged to be the accessory punctum. CASE SUMMARY: A 39-year-old male patient with no underlying disease and no ophthalmologic history visited our clinic with right eye epiphora of 2 weeks duration. On slit lamp examination, double puncta were observed in the right lower eyelid and the remaining puncta were normal. On lacrimal syringing test and dacryocystography were performed and revealed incomplete obstruction with partial narrowing of the nasolacrimal duct. Silicone tube intubation was performed through the right lower medial punctum and symptoms improved postoperatively. CONCLUSIONS: The present case is an unusual case of double lacrimal puncta which has not been reported in Korea. Unlike the previous literature, the lateral, rather than the medial, punctum was judged to be the accessory punctum. Because accessory punctm can be present on the lateral side, it is necessary to distinguish between the accessory punctm and the main punctum through the accurate dacryocystography and lacrimal syringing test for the treatment of the patient.
Adult ; Eyelids ; Humans ; Intubation ; Korea ; Lacrimal Apparatus ; Lacrimal Apparatus Diseases ; Male ; Nasolacrimal Duct ; Silicon ; Silicones ; Slit Lamp

PURPOSE: When there is a mass in the superior temporal orbit area, a lacrimal gland tumor should be suspected. We report a rare case of orbital lymphatic malformation that was histologically diagnosed in a patient with typical clinical features of the lacrimal gland. CASE SUMMARY: A 55-year-old female with no underlying disease and no ophthalmic history visited our clinic with a right upper eyelid edema associated with an enlarged painless eyelid mass 1 month prior to her visit. The patient stated that she discovered the mass 1 year previously.The palpebral lobe of the lacrimal gland protruded slightly with congestion of the surrounding conjunctiva. Enhanced computed tomography showed a 3 cm well-defined heterogeneous mass in the right lacrimal gland area and several well-defined round calcifications within the mass. Orbital tissue or bone involvement was not observed. The pleomorphic adenoma of the lacrimal gland was the most clinically suspicious, so complete resection of the mass was performed using lateral orbitotomy. Histopathologically, lymphangioma (lymphatic malformation) originating from the lacrimal gland was diagnosed. CONCLUSIONS: Orbital lymphatic malformation can occur in the lacrimal gland. The present case showed that differential diagnosis can reveal the presence of an adult lacrimal gland tumor.
Adenoma, Pleomorphic ; Adult ; Conjunctiva ; Diagnosis, Differential ; Edema ; Estrogens, Conjugated (USP) ; Eyelids ; Female ; Humans ; Lacrimal Apparatus ; Lymphangioma ; Middle Aged ; Orbit

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that affects mainly salivary and lacrimal glands, but its cause remains largely unknown. Clinical data indicating that SS occurs in a substantial proportion of patients with lupus points to common pathogenic mechanisms underlying the two diseases. To address this idea, we asked whether SS develops in the lupus-prone mouse strain sanroque (SAN). Owing to hyper-activation of follicular helper T (Tfh) cells, female SAN mice developed lupus-like symptoms at approximately 20 wk of age but there were no signs of SS at that time. However, symptoms typical of SS were evident at approximately 40 wk of age, as judged by reduced saliva flow rate, sialadenitis, and IgG deposits in the salivary glands. Increases in serum titers of SS-related autoantibodies and numbers of autoantibody-secreting cells in cervical lymph nodes (LNs) preceded the pathologic manifestations of SS and were accompanied by expansion of Tfh cells and their downstream effector cells. Thus, our results suggest that chronic dysregulation of Tfh cells in salivary gland-draining LNs is sufficient to drive the development of SS in lupus-prone mice.
Animals ; Autoantibodies ; Autoimmunity ; Disease Models, Animal ; Female ; Humans ; Immunoglobulin G ; Lacrimal Apparatus ; Lupus Erythematosus, Systemic ; Lymph Nodes ; Mice ; Saliva ; Salivary Glands ; Sialadenitis

Aging is a complex process associated with dysregulation of the immune system and low levels of inflammation, often associated with the onset of many pathologies. The lacrimal gland (LG) plays a vital role in the maintenance of ocular physiology and changes related to aging directly affect eye diseases. The dysregulation of the immune system in aging leads to quantitative and qualitative changes in antibodies and cytokines. While there is a gradual decline of the immune system, there is an increase in autoimmunity, with a reciprocal pathway between low levels of inflammation and aging mechanisms. Elderly C57BL/6J mice spontaneously show LGs infiltration that is characterized by Th1 but not Th17 cells. The aging of the LG is related to functional alterations, reduced innervation and decreased secretory activities. Lymphocytic infiltration, destruction, and atrophy of glandular parenchyma, ductal dilatation, and secretion of inflammatory mediators modify the volume and composition of tears. Oxidative stress, the capacity to metabolize and eliminate toxic substances decreased in aging, is also associated with the reduction of LG functionality and the pathogenesis of autoimmune diseases. Although further studies are required for a better understanding of autoimmunity and aging of the LG, we described anatomic and immunology aspects that have been described so far.
Aged ; Aging ; Allergy and Immunology ; Animals ; Antibodies ; Atrophy ; Autoimmune Diseases ; Autoimmunity ; Cytokines ; Dilatation ; Eye Diseases ; Humans ; Immune System ; Inflammation ; Lacrimal Apparatus ; Mice ; Ocular Physiological Phenomena ; Oxidative Stress ; Pathology ; Tears ; Th17 Cells

BACKGROUND/AIMS: This study investigated the clinical and pathological features of immunoglobulin G4 (IgG4)-related ophthalmic disease. To clarify the features, we compared IgG4-related ophthalmic disease and orbital inflammatory pseudotumor. METHODS: We retrospectively reviewed the medical records of 103 patients who were initially diagnosed with orbital inflammatory pseudotumor, and identified 16 cases in which the diagnosis was based on surgical biopsy and for which data in medical records were sufficient for analysis. Immunohistochemical staining of pathological specimens for IgG and IgG4 was performed. Finally, six of IgG4-related ophthalmic disease patient and 10 of orbital inf lammatory pseudotumor patient were analyzed. RESULTS: The IgG4-related ophthalmic disease group had more IgG4-positive plasma cells and a higher IgG4/IgG plasma cell ratio than the orbital inflammatory pseudotumor group. Collagenous fibrosis and lacrimal gland involvement were significantly more frequent in the IgG4-related ophthalmic disease group. Dense lymphocyte infiltration, obliterative phlebitis, and bilateral lesions were more frequent in IgG4-related ophthalmic disease, but the differences were not significant. The recurrence-free period was shorter in the IgG4-related ophthalmic disease group (p = 0.035). CONCLUSIONS: The location of the lesion (lacrimal gland), count and ratio of IgG4-positive plasma cells, and collagenous fibrosis aid the diagnosis of IgG4-related ophthalmic disease in patients with idiopathic orbital mass-like lesions. In addition, maintenance therapy should be considered in patients with IgG4-related ophthalmic disease to prevent recurrence.
Biopsy ; Collagen ; Diagnosis ; Fibrosis ; Humans ; Immunoglobulin G ; Immunoglobulins* ; Lacrimal Apparatus ; Lymphocytes ; Medical Records ; Orbit* ; Orbital Pseudotumor* ; Phlebitis ; Plasma Cells ; Recurrence ; Retrospective Studies