Color Doppler Imaging Features of the Lacrimal Sac in Health and Diseased States.

PURPOSE: The objective of this study is to present Color Doppler imaging (CDI) features of the lacrimal sac in normal and diseased states. METHODS: Prospective study was performed on 20 lacrimal sacs of 20 eyes of 10 patients who underwent Color Doppler imaging at a tertiary care Dacryology service over a period of 6 months. All the patients were subjected to Duplex doppler scanning of the lacrimal sacs. Of the 20 lacrimal drainage systems studied, 8 were normal, 8 had primary acquired nasolacrimal duct obstruction (PANDO) and 4 were that of acute dacryocystitis (AcDac). Patient demographics, clinical presentation, duration of the disease and Color Doppler vascular characteristics like peri-sac vascular flow, peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI), arterial spectral waveforms and sac dimensions and wall thickness were analyzed. RESULTS: The vascular flow around the lacrimal sac was increased with higher flow velocities in PANDO as compared to normal and grossly enhanced in AcDac. Flow disturbances were also quite discernible in AcDac. The mean PSV and EDV were 9 & 3.87 cm/sec, 13.07 & 4.63 cm/sec and 18 & 8.5 cm/sec in normal, PANDO and AcDac, respectively. The mean vascular resistivity index increased in patients with PANDO (0.67) and decreased in AcDac (0.53) as compared to the normal (0.57). The arterial spectral waveforms in PANDO and AcDac showed low pulsatility, but the systolic peaks were sharper with more continuous forward flow through diastole in AcDac. This reflects vascular dilatation and reduced resistance to flow in AcDac. CONCLUSION: Characteristic Color Doppler flow parameters can be demonstrated in patients with PANDO and acute dacryocystitis. Color Doppler techniques have the potential to enhance the understanding of lacrimal drainage pathophysiology.

Characterization and Management of Inflammatory Eye Disease in Patients with Hidradenitis Suppurativa.

Purpose: To assess the spectrum and treatment outcomes of inflammatory eye disease (IED) in subjects with hidradenitis suppurativa (HS).Methods: We conducted a single center retrospective chart review of 236 patients with HS seen for ophthalmic examination between 2013 and 2018.Results: Of 236 subjects with HS, 22 subjects (9.3%) were found to have IED. Seven of 22 subjects had more than one IED diagnosis. Anterior uveitis was the most common type of IED (40.9% of subjects with IED). Episcleritis, optic neuritis, keratitis, scleritis, intermediate and posterior uveitis, trochleitis, and dacryoadenitis were also observed. Of subjects with HS and IED, 59.1% did not have any other inflammatory or autoimmune disease that could explain the etiology of their IED. Eleven patients with IED were treated with systemic immunosuppression, with IED as the principal factor directing treatment in three patients.Conclusions: IED may be independently associated with HS and may benefit from systemic immunosuppression.

Ectopic lacrimal gland in the lacrimal sac mimicking tumour: literature review.

An 80-year-old man referred with repeated episode of dacryocystitis from the left lacrimal drainage system and palpable swelling. For many years, he has being presented with epiphora unilaterally with chronic dacryocystitis. Investigations with dye-test revealed subocclusion of the natural passage of the tears, and CT and MRI scans revealed solid mass in the lacrimal sac. The lacrimal sac was opened by endonasal endoscopic approach, the sacral mass was identified and completely removed. The histopathological examination showed lacrimal gland in ectopic position. Patient followed for 18 months with complete recovery of symptoms. In our differential diagnosis, the ectopic lacrimal gland is also identified, when a mass in the lacrimal sac and duct is present. Successful surgical excision required considerable multidisciplinary teamwork between ophtalmologist-ENT (Otolaryngologist) and radiologist. Endonasal endoscopic approach is perfectly safe with direct control and ensures a smooth postoperative recovery.

Development of lacrimal gland inflammation in the mouse model of herpes stromal keratitis.

Herpes stromal keratitis (HSK) is a chronic immunoinflammatory condition which develops in response to recurrent herpes simplex virus-1 (HSV-1) infection of the cornea. Patients with HSK often demonstrate the concurrence of corneal desiccation and the loss of blink reflex. However, the relationship between severity of HSK, level of basal tears and inflammation of the lacrimal gland is mostly unexplored. In this study, we compared these variables in extraorbital lacrimal gland (EoLG) after corneal HSV-1 infection in the C57BL/6J mouse model. Our results showed a significant reduction in the volume of tears in infected eyes during the development of HSK. Extensive architectural damage to EoLG, presumably caused by a massive influx of interferon-gamma secreting T cells, was observed during clinical disease period of HSK. A positive correlation between the decrease in tear volume, severity of HSK and the damage to EoLG were evident in infected mice. The presence of infectious virus measured in EoLG during pre-clinical, but not clinical disease period of HSK, suggested that viral cytopathic effects are not the major contributors of extensive damage seen in EoLG. Furthermore, topical administration of lacritin peptide delayed but did not prevent the decrease in tears in HSV-1 infected mice, and had no significant effect in either reducing the severity of HSK or T cell infiltration in EoLG of infected mice. Together, our results showed an interplay between the severity of HSK, inflammation of EoLG, and the reduced level of tears after corneal HSV-1 infection.

Clinical significance of ocular manifestations in granulomatosis with polyangiitis: association with sinonasal involvement and damage.

Ocular involvement is present in 50-60% of granulomatosis with polyangiitis (GPA) patients and can affect any part of the ocular globe. The present study describes ophthalmologic manifestations, association with systemic symptoms, disease activity and damage in GPA. A cross-sectional study was conducted including patients with GPA who underwent rheumatologic and ophthalmologic evaluation. Demographics, comorbidities, ophthalmologic symptoms, serologic markers, radiographic studies, disease activity and damage were assessed. Descriptive statistics, correlation, univariable logistic regression analyses, Student's t, Mann-Whitney U, Chi-square and Fisher's exact tests were performed. Fifty patients were included, 60% female, the median age was 56 years, disease duration 72.5 months. Nineteen (38%) patients had ocular manifestations at GPA diagnosis, scleritis being the most frequent; 27 (54%) patients presented ocular involvement during follow-up, repeated scleritis and dacryocystitis being the most common manifestations. Concomitant ophthalmic and sinonasal involvement was present in 12 (24%). Ocular and ENT damage occurred in 58% and 70%, respectively. Epiphora and blurred vision were the most frequent symptoms; scleromalacia and conjunctival hyperemia (27%) the most frequent clinical abnormalities. Ocular involvement at diagnosis was associated with concomitant ocular and sinonasal involvement at follow-up (OR 4.72, 95% CI 1.17-19.01, p = 0.01). Ocular involvement at follow-up was associated with age at GPA diagnosis (OR 0.94, 95% CI 0.90-0.99, p = 0.03), VDI (OR 1.29, 95% CI 1.03-1.61, p = 0.02), and ENT damage (OR 5.27, 95% CI 1.37-20.13, p = 0.01). In GPA, ocular involvement is frequent, therefore, non-ophthalmologist clinicians should be aware of this manifestation to reduce the risk of visual morbidity and organ damage.

Surfactant proteins: Role in lacrimal drainage disorders.

Surfactants are complex mixtures of phospholipids and proteins produced by type II alveolar cells of the lungs and play a crucial role in pulmonary physiology. Six types of surfactant proteins (SP) are known; SP-A, SP-B, SP-C, SP-D, SP-G and SP-H. The major role of SP is in reducing surface tension and various immunological functions. SP-A, SP-B, SP-C and SP-D have been demonstrated in the tear film and the epithelium of the lacrimal sac (LS) and nasolacrimal ducts (NLD). All surfactant proteins except SP-G were also isolated from the canalicular tissues. The authors hypothesize that surfactant proteins play a significant role in the pathogenesis of lacrimal drainage disorders; functional nasolacrimal duct obstruction (FNLDO) and infective dacryocystitis.

Comparing Outcomes of the Standard Technique of Endoscopic DCR with Its Modifications: A Retrospective Analysis.

OBJECTIVE: To compare the outcomes of various techniques of endoscopic dacryocystorhinostomy (DCR). STUDY DESIGN: Retrospective case record analysis. SETTINGS: Tertiary care referral center. SUBJECT AND METHODS: Retrospective analysis of case records was carried out pertaining to the period from January 1996 to September 2017 with respect to patients who had undergone endoscopic DCR with either the standard technique or one of its modifications. Case notes showing well-documented preoperative evaluation, operative details, postoperative assessment, and minimum 6-month follow-up were considered. The outcomes were measured on the basis of patients' postoperative symptoms, clinical examination, and sac-syringing results. RESULTS: A total of 423 patients were included in the study. Of these, 169 underwent standard endoscopic DCR; 87, endoscopic DCR with stent; 19, endoscopic DCR with mitomycin C; 62, powered DCR; 29, laser-assisted DCR; and 57, balloon DCR. There was no statistically significant difference in success rates, recurrences, or complications of various techniques at 3 or 6 months. Mean operating time was lowest for balloon DCR (mean ± SD, 27.1 ± 3.1 minutes), followed by standard endoscopic DCR (38.2 ± 3.6 minutes; P = .001). CONCLUSION: Standard endoscopic DCR and its more sophisticated modifications were equally effective and safe in managing distal nasolacrimal drainage obstruction. Balloon DCR, followed by standard endoscopic DCR, was significantly faster than other techniques.

Regeneration of Lacrimal Gland Function to Maintain the Health of the Ocular Surface.

Dry eye is a multifactorial disease that is one of the most common diseases worldwide. A major cause of dry eye is the deficiency of aqueous tears, which are mainly secreted from the lacrimal gland. The lacrimal gland plays an important role in maintaining the health of the ocular surface and protecting it from environmental exposure. Dry eye can lead to ocular irritation and discomfort, as well as severe ocular surface diseases (e.g., ocular infections, corneal ulcerations, and ocular surface keratinization). These severe diseases can be induced by an atrophied or injured lacrimal gland; current therapies cannot completely restore the function of lacrimal gland. To develop more definitive therapies, it is important to understand lacrimal gland biology at the molecular level, as well as inflammatory processes affecting the function of the gland. During severe inflammation, the tissue structure of the lacrimal gland is destroyed; it is replaced by scar formation during wound healing, which leads to lacrimal gland dysfunction. Using an animal model of lacrimal gland dysfunction, many investigators have studied molecular mechanisms of inflammation in the lacrimal gland. To restore lacrimal gland function, the lacrimal acini must be restored in their niche. Notably, organ transplantation therapies have been reported to restore lacrimal gland function, directly or indirectly, in animal models. In this review, we describe the current understanding of the lacrimal gland as the therapeutic target for dry eye diseases, as well as recent advances in the field of lacrimal gland cell-based therapy to treat severe dry eye diseases.

Inflammatory Response in Dry Eye.

Purpose: Dry eye is a major ocular pathology worldwide. Although dry eye is a multifactorial disease, recent studies have shown that chronic immunologic processes have a pivotal role in its pathogenesis, characterized by the infiltration of immune cells in the lacrimal glands, elevated levels of tear inflammatory cytokines, and increased density of immune cells in the cornea and conjunctiva. This review describes the recent advances in understanding the relationship between dry eye and inflammation. Methods: This narrative review is based on searches of recent international literature using terms related to the immune response in dry eye, and includes clinical trials, animal experiments, and expert reviews. Results: Although dry eye presents clinically as tear film instability associated with corneal/conjunctival epithelial disorders, Meibomian gland dysfunction, and decreased visual function, recent laboratory and clinical studies have indicated inflammation in the lacrimal glands, Meibomian glands, conjunctiva, cornea, and aqueous tears. Furthermore, inflammation at these locations leads to conjunctival goblet cell apoptosis, corneal epithelial barrier disruption, and corneal nerve damage. These inflammatory outcomes can be exacerbated by intrinsic and extrinsic factors, such as aging, sex steroid hormone, autoimmune diseases, contact lens use, visual display terminals, and dry environment. Conclusions: Recent advances in dry eye research have revealed the inflammatory process and its pathogenesis, which has been proposed as an "inflammatory vicious cycle" of dry eye. Comprehensive assessment of dry eye based on inflammation will improve the selection of treatments and help break the inflammatory cycle in clinical settings.

NOD and NOR mice exhibit comparable development of lacrimal gland secretory dysfunction but NOD mice have more severe autoimmune dacryoadenitis.

The male Non-Obese Diabetic (NOD) mouse is an established model of autoimmune dacryoadenitis characteristic of Sjögren's Syndrome (SS), but development of diabetes may complicate studies. The Non-Obese Diabetes Resistant (NOR) mouse is a MHC-II matched diabetes-resistant alternative, but development of autoimmune dacryoadenitis is not well-characterized. We compare features of SS in male NOD and NOR mice at 12 and 20 weeks. Stimulated tear secretion was decreased in 12 week NOD relative to BALB/c mice (p < 0.05), while by 20 weeks both NOD and NOR showed decreased stimulated tear secretion relative to BALB/c mice (p < 0.001). Tear CTSS activity was elevated in NOD and NOR relative to BALB/c mice (p < 0.05) at 12 and 20 weeks. While NOD and NOR lacrimal glands (LG) showed increased LG lymphocytic infiltration at 12 and 20 weeks relative to BALB/c mouse LG (p < 0.05), the percentage in NOD was higher relative to NOR at each age (p < 0.05). Gene expression of CTSS, MHC II and IFN-γ in LG were significantly increased in NOD but not NOR relative to BALB/c at 12 and 20 weeks. Redistribution of the secretory effector, Rab3D in acinar cells was observed at both time points in NOD and NOR, but thinning of myoepithelial cells at 12 weeks in NOD and NOR mice was restored by 20 weeks in NOR mice. NOD and NOR mice share features of SS-like autoimmune dacryoadenitis, suggesting common disease etiology. Other findings suggest more pronounced lymphocytic infiltration in NOD mouse LG including increased pro-inflammatory factors that may be unique to this model.

Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting.

Dry eye disease (DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED-related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase-9, human leucocyte antigen-DR or intercellular adhesion molecule-1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti-inflammatory compounds. For instance, cyclosporine, already approved in the United States, has recently been authorized in Europe to treat DED associated with severe keratitis. In addition, other agents such as corticosteroids, doxycycline and essential fatty acids, through their anti-inflammatory properties, show encouraging results. We now have a clearer understanding of the inflammatory processes involved in DED, and there is hope that the still emerging preclinical/clinical findings will be translated into new and highly effective therapies for patients in the near future.

Primary vs Secondary Endoscopic Dacryocystorhinostomy for Acute Dacryocystitis With Lacrimal Sac Abscess Formation: A Randomized Clinical Trial.

Importance: Endoscopic dacryocystorhinostomy (EN-DCR) is emerging as the preferred procedure in the management of nasolacrimal duct obstructions. However, its safety and long-term efficacy in the setting of acute dacryocystitis with lacrimal sac abscess have not been well studied. Objective: To compare outcomes of EN-DCR as primary treatment with EN-DCR as a secondary treatment after percutaneous drainage of lacrimal sac abscess in acute dacryocystitis. Design, Setting, and Participants: This randomized clinical trial was conducted from October 1, 2012, to October 31, 2015, at a tertiary ophthalmic center. The assessors of success at postoperative year 1 were masked to the procedures received by the participants. All surgical procedures were performed by 2 oculoplastic surgeons with different levels of EN-DCR experience. Eligible participants had acute dacryocystitis and lacrimal sac abscess presenting within 2 weeks of onset, who were 18 to 90 years of age. Analysis was of the intention-to-treat population. Interventions: Patients were allocated by block randomization to receive either percutaneous drainage of lacrimal sac abscess followed by EN-DCR after the acute episode subsided (control group) or primary EN-DCR within 2 weeks of presentation (intervention group). Both groups received a course of empirical systemic antibiotics (amoxicillin and clavulanic acid, 375 mg, to be taken 3 times a day for 1 week). Main Outcomes and Measures: Primary outcomes were time from presentation to documentation of symptom resolution and recurrence within 3 months. Results: Thirty-two patients were randomized equally into 2 treatment arms (control and intervention). The mean (SD) age of patients was 61 (13) years, and there was a predominance of women (27 [84%]). The mean (SD) time to symptom resolution was 13.8 (5.8) days in the intervention group compared with 31.7 (27.1) days in the control group (mean difference, 17.9; 95% CI, 3.71-32.01; P = .02). The mean (SD) time to surgery in the intervention group was shorter at 11.9 (6.3) days compared with 45.6 (30.1) days in the control group (mean difference, 33.6; 95% CI, 17.92-49.33; P < .001). Recurrences occurred once in the control group and did not occur in the intervention group. No differences in operation time and complications between the 2 groups were identified. The anatomical and functional success was 87.5% (14 of 16 cases) in both groups at postoperative year 1. Conclusions and Relevance: Primary EN-DCR in acute dacryocystitis with lacrimal sac abscess results in faster resolution compared with secondary treatment. No differences in recurrence, safety, or outcomes at postoperative year 1 were noted between the 2 treatment groups.

Changes in Tear Film Characteristics in Patients With Idiopathic Dacryoadenitis.

PURPOSE: To evaluate the tear-film meniscus with optical coherence tomography (OCT) in patients with idiopathic dacryoadenitis and to determine its relationships with the clinical tests. METHODS: Sixteen patients with unilateral idiopathic dacryoadenitis were included in the study. Patients with idiopathic dacryoadenitis with affected sites (group 1), with contralateral sites (group 2) and healthy participants (group 3) completed the ocular surface disease index before optical coherence tomography determination of tear meniscus height and tear meniscus area. These were followed by measurements of tear breakup time, fluorescein staining, and Schirmer test. Finally, surgical debulking or incisional biopsies were conducted. RESULTS: Tear meniscus height and tear meniscus area were the lowest in patients with affected sites (group 1) among the 3 groups (p < 0.05). Breakup time was the shortest in group 1 (p < 0.05). In the group 1, breakup time, fluorescein staining score, and histopathological phases were significantly correlated with tear meniscus height and tear meniscus area (p < 0.05). CONCLUSIONS: Tear function was significantly disturbed in idiopathic dacryoadenitis. Tear menisci volumes measured by optical coherence tomography may assess the tearing function in patients with idiopathic dacryoadenitis.

Preferential M2 macrophages contribute to fibrosis in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease.

IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is characterized by bilateral swelling of glandular tissues with extensive fibrosis, and is immunologically considered a Th2-predominant disease. Recent studies reported that alternatively activated (M2) macrophages enhanced Th2 immune responses and fibrosis by production of pro-fibrotic factors (IL-10, IL-13 and CCL18). Therefore, we examined the association between M2 macrophages and fibrosis in submandibular glands from 7 patients with IgG4-DS, 10 patients with chronic sialoadenitis, 10 patients with Sjögren's syndrome, and 10 healthy subjects. The number of M2 macrophages in SMGs from patients with IgG4-DS was also significantly higher than in the other groups. Double immunofluorescence staining showed that IL-10 and CCL18 expression co-localized with M2 macrophage-marker (CD163). Furthermore, the SMG fibrosis score was positively correlated with the frequency of M2 macrophages in only IgG4-DS. These results indicate that IL-10 and CCL18 secreted by preferential M2 macrophages possibly play a key role in the development of severe fibrosis in IgG4-DS.

[Peculiarities of tear production in patients with dacryoadenitis].

The influence of chronic adenitis and its surgical treatment on tear production and osmolarity was studied. A long-term follow-up (2-65 months) after lacrimal gland extirpation showed a trend for recovery of both basal and reflex lacrimation. Comparison of complaints and functional and pathohistological results allowed to consider retention cysts as a risk factor for dry eye syndrome in the postoperative period.

Incision-sparing management of canaliculitis.

PURPOSE: To report our results of canaliculitis treatment with our incision-sparing technique which includes dilation of the punctum and compression of the canaliculus to express the sulphur granules, curettage and irrigation of the canaliculus with antibiotic solutions, and topical antibiotic use. METHODS: The medical records of all patients treated for canaliculitis between October 2009 and March 2013 were rewiewed. The punctum of affected canaliculus was dilated under local anesthesia. Then, starting just distal to common canaliculus, the horizontal canaliculus was compressed along its entire length using either a forceps or a cotton tip applicator on the conjunctival surface and a curette on the skin. Compression was repeated until no more sulphur granules appeared and the swelling of the canaliculus disappeared. A chalazion curette was inserted into canaliculus to evacuate any residual concretions. The canaliculus were irrigated with antibiotic solutions and the patients were prescribed topical antibiotic solutions for one month Patients with follow-up less than 3 months after the intervention were excluded from the study. RESULTS: Nine patients met criteria for canaliculitis. There were 1 male and 8 female patients. Median age of the patients was 53 years (range 36-72 years). All patients had unilateral lower canaliculitis. Mean duration of the symptoms was 13.4 months (range 4-36 months). We followed up all patients for at least 3 months after the intervention. The signs and symptoms resolved completely in all patients within 1 month and recurrence was not observed in any patient. No patients reported epiphora after the procedure. CONCLUSION: Our incision-sparing technique is effective in the treatment of canaliculitis. We suggest that minimally invasive or incision-sparing techniques be attempted before canaliculotomy to decrease postoperative complications rates.

Effect of mitomycin C on success rate in dacryocystorhinostomy with silicone tube intubation and improper flaps.

PURPOSE: To assess the effect of mitomycin C on surgical success rate of dacryocystorhinostomy and silicone intubation in patients with improper flaps. METHODS: The study was a randomized clinical trial. The patients with indication for dacryocystorhinostomy surgery with silicone intubation (inappropriate lacrimal sac or nasal mucosal flaps during surgery and/or history of dacryocystitis in the past 3 months) were randomly assigned to application of mitomycin C (0.02%) on surgical flaps (group A) or a control group without mitomycin C application (group B). Main outcome measures were subjective symptomatic improvement and result of irrigation test at last follow-up visit. RESULTS: The study enrolled 88 patients (88 eyes); there were 42 patients in group A and 46 patients in group B. There was an average follow-up of 10 months (range 6-15 months) following surgery. Significant improvement (no tearing with patent lacrimal system in irrigation) was observed in 31 patients (73.8%) in group A and 32 patients (69.6%) in group B. There was no statistically significant difference in no improvement (no change in tearing state and obstruction in irrigation test), relative improvement (decreased tearing and passage of fluid with force in irrigation test), and significant improvement rate between the 2 groups of study (p>0.05). CONCLUSIONS: Application of mitomycin C on surgical flaps during dacryocystorhinostomy surgery with silicone intubation in patients with improper flaps has no proven beneficial effect on success rate of surgery.

Acute dacryocystitis associated with epstein-barr virus infection.

Acute dacryocystitis is a rare complication of infectious mononucleosis with only three previous reports in the English literature. We present two further children with acute dacryocystitis and clinical and laboratory features of Epstein-Barr Virus related infectious mononucleosis. Both were treated with systemic antibiotics and one child additionally required surgical drainage of a lacrimal sac abscess. Both children made a complete recovery without any lacrimal symptoms. Acute dacryocystitis is uncommon in children without a history of congenital nasolacrimal duct obstruction, and an underlying systemic condition such as infectious mononucleosis should be suspected. In such patients, dacryocystitis can be expected to resolve without symptoms of nasolacrimal duct obstruction and dacryocystorhinostomy is seldom required.

Dysfunction of lacrimal and salivary glands in Sjögren's syndrome: nonimmunologic injury in preinflammatory phase and mouse model.

Sjögren's syndrome (SjS) is a chronic autoimmune disorder characterized by dry eyes and dry mouth due to dacryoadenitis and sialoadenitis with SS-A/Ro and/or SS-B/La autoantibodies in genetically predisposed individuals. Destruction of lacrimal and salivary glands by autoimmune reactions may lead to clinical manifestation. However, the mechanisms behind the decreased volume of secretions in tears and saliva are complex and are not fully understood. Exocrine gland dysfunction may precede autoimmunity (acquired immunity) or represent a process independent from inflammation in the pathogenesis of SjS. The preceded functional and morphologic changes of those tissues by nonimmunologic injury before the development of inflammation at the sites of target organs have been implicated. This paper focuses on the several factors and components relating to glandular dysfunction and morphologic changes by nonimmunologic injury during the preinflammatory phase in mouse model, including the factors which link between innate immunity and adaptive immunity.