scRNA-Seq: First Atlas and Cellular Landscape of Lacrimal Sac: Implications in Primary Acquired Nasolacrimal Duct Obstruction Pathogenesis.

Purpose: The aim of this study was to describe the transcriptional changes of individual cellular components in the lacrimal sac in patients with primary acquired nasolacrimal duct obstruction (PANDO) and attempt to construct the first lacrimal sac cellular atlas to elucidate the potential mechanisms that may drive the disease pathogenesis. Methods: Lacrimal sac samples were obtained intra-operatively during the endoscopic dacryocystorhinostomy (EnDCR) procedure from five patients. Single-cell RNA sequencing was performed to analyze each individual cell population including epithelial and immune cells during the early inflammatory and late inflammatory phases of the disease. Results: Eleven cell types were identified among 25,791 cells. T cells and B cells were the cell populations with the greatest variation in cell numbers between the two phases and were involved in immune response and epithelium migration-related pathways. The present study showed that epithelial cells highly expressed the genes of senescence-associated secretory phenotype (SASP) and were involved in influencing the inflammation, neutrophil chemotaxis, and migration during the late inflammatory stage. Enhanced activity of CXCLs-CXCRs between the epithelial cells and neutrophils was noted by the cell-cell communication analysis and is suspected to play a role in inflammation by recruiting more neutrophils. Conclusions: The study presents a comprehensive single-cell landscape of the lacrimal sac cells in different phases of PANDO. The contribution of T cells, B cells, and epithelial cells to the inflammatory response, and construction of the intercellular signaling networks between the cells within the lacrimal sac has further enhanced the present understanding of the PANDO pathogenesis.

Etiopathogenesis of primary acquired nasolacrimal duct obstruction (PANDO).

Primary acquired nasolacrimal duct obstruction, or PANDO, is a common adult lacrimal drainage disorder. The current treatment modality of dacryocystorhinostomy to bypass the obstructed nasolacrimal duct has excellent outcomes. However, the understanding of the disease etiopathogenesis needs to be revisited. There are not many studies that specifically assessed any hypothesis or ones that convincingly put forth the presumed or confirmed interpretations regarding the PANDO pathogenesis or the mechanisms or pathways involved therein. Histopathological evidence points to recurrent inflammation of the nasolacrimal duct, subsequent fibrosis, and the resultant obstruction. The disease etiopathogenesis is considered multifactorial. Several implicated suspects include anatomical narrowing of the bony nasolacrimal duct, vascular factors, local hormonal imbalance, microbial influence, nasal abnormalities, autonomic dysregulation, surfactants, lysosomal dysfunction, gastroesophageal reflux, tear proteins, and deranged local host defenses. The present work reviewed the literature on the etiopathogenesis of primary acquired nasolacrimal duct obstruction (PANDO) to gain insights into the present state of the understanding and the high-value translational implications of precisely decoding the disease etiology.

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.

Transconjunctival versus Transcutaneous Injection of Botulinum Toxin into the Lacrimal Gland to Reduce Lacrimal Production: A Randomized Controlled Trial.

The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally (n = 15, 25 eyes) or transcutaneously (n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer's I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.

Clinical and Demographic Characteristics of Tearing in Patients after Radioiodine Ablation for Differentiated Thyroid Cancer.

Background: Radioiodine ablation is a frequent procedure for the management of thyroid cancer. In several cases, this treatment is followed by secondary acquired nasolacrimal duct obstruction (SALDO). Risk factors for the development of SALDO are not defined yet.Aim - to provide clinical and demographic characteristics of tearing in patients after radioiodine treatment.Materials and methods: Material was obtained by a phone survey of 588 patients who underwent radioiodine treatment. Age and gender of the respondent, strength of administered medication, and time since the end of treatment were taken into account. Patients were asked if they had dry mouth and/or tearing at the time of the survey. Differences in values were found using parametric and nonparametric criteria, Pearson's χ2 test. Differences were considered statistically significant at p ≤ 0.05.Results: Severe tearing was reported by 8.8% of patients after single-dose radioiodine treatment and 23.9% of patients after repeated one. The age of patients with severe tearing and without it showed statistically significant difference in patients after single-dose radioiodine treatment and no statistically significant difference in patients after repeated radioiodine treatment. Administration of 4 GBq or more in patients aged 61-71 years results in 4-fold increase of the risk of severe tearing. Dry mouth causes 3.6-fold increase of the risk of developing severe tearing.Conclusion: Finding risk factors for SALDO development after radioiodine therapy in the future will contribute to an individualized approach to the prevention of this complication. Development of preventive measures is one of the tasks facing researchers.

Detection & analysis of inflammatory cytokines in tears of patients with lacrimal duct obstruction.

Background & objectives: Tear proteomic changes can be a candidate etiopathogenesis of lacrimal duct obstruction diseases (LDODs). Studies on proteomics have focused primarily on nasolacrimal duct obstruction, and some specific inflammatory cytokines such as interferon (IFN)-α2a, interleukin (IL)-8 and IL-10, have not been investigated. In addition, differences in inflammatory cytokines in tears according to the LDOD subtype have not been reported. This study aimed to quantitatively compare inflammatory cytokines in tears from patients with LDOD and investigate tear-cytokine differences among different LDOD subtypes. Methods: Tear samples were collected from both eyes of 30 patients with unilateral LDOD: five patients with prelacrimal obstruction, five with acute dacryocystitis and 20 with chronic dacryocystitis. The contralateral eyes were used as controls. IFN-α2a, IFN-ß, IFN-γ, IL-17A, IL-6, IL-8, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF)-A, induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1) were quantified in all samples. Results: The expression of eight cytokines (except for IP-10 and MCP-1) were significantly increased in the affected eyes compared with those in the control eyes. The levels of nine inflammatory cytokines (except for IP-10) in the affected eyes of patients with chronic dacryocystitis were higher than those in the affected eyes of patients with prelacrimal obstruction. In addition, patients with chronic dacryocystitis presented significantly higher IFN-γ level than those with prelacrimal obstruction or acute dacryocystitis. Interpretation & conclusions: Specific pro-inflammatory cytokines were increased in tears of patients with LDOD compared with those in the controls. The specific cytokine profiles observed in the tears of individuals with different LDOD subtypes may be associated with the unique aetiopathogenesis of these conditions.

Alteration of Tear Cytokine Expressions in Primary Acquired Nasolacrimal Duct Obstruction - Potential Insights into the Etiopathogenesis.

Purpose: To investigate the presence and level of 35 distinct cytokines in the tear fluid obtained from patients with primary acquired nasolacrimal duct obstruction (PANDO) and compare it with controls in an effort to understand the disease etiopathogenesis.Methods: Standard protocols were used for collecting tears from 60 eyes (20 diseased eyes and 20 healthy fellow eyes of unilateral PANDO, 20 control eyes of healthy subjects). A total of 35 analytes involved in inflammation, angiogenesis and wound healing were assessed by multiplex ELISA. Alterations in the tear levels of cytokines in PANDO and their comparison with the levels in the non-diseased fellow eye and healthy volunteers were noted. STRING analysis was used to assess the involved biological pathways of the altered cytokines. Linear mixed effect model was used for statistical analysis. A P value of <0.05 was considered significant.Results: There was significant upregulation of 10 pro-inflammatory cytokines in tears from diseased eyes of PANDO patients in comparison with the non-diseased controls and include matrix metalloproteinase 9 (MMP 9), serpin E1, Interleukin-6 (IL-6), hepatocyte growth factor (HGF), vascular endothelial growth factor-A and R2 (VEGF-A, VEGF R2), platelet-endothelial cell adhesion molecule (PECAM-1), c-reactive protein (CRP), chemokine ligand 2 (CCL2) and platelet-derived growth factor- AA (PDGF-AA). Amongst the anti-inflammatory cytokines, three were significantly upregulated in diseased eyes of PANDO patients in comparison with the non-diseased controls and include granulocyte-colony stimulating factor (G-CSF), retinol binding protein 4 (RBP4) and tissue inhibitor of metalloproteinases -1 (TIMP-1). There were no significant differences between the control eyes of the diseased patient and control eyes of healthy subjects. Based on the significantly altered cytokines, string analysis revealed that the biological pathways involved in the etiopathogenesis of PANDO include inflammation, angiogenesis, negative regulation of apoptosis, cellular proliferation and hormonal regulation.Conclusions: In cases of PANDO, dysregulation of certain cytokines was disease specific. Biological pathways reflect a possible link and interaction between the inflammatory cytokines with vasculature and hormonal microenvironments of the lacrimal drainage system, which in a way is bringing three promising candidates in the PANDO etiopathogenesis on a common ground.

Nasolacrimal stent with shape memory as an advanced alternative to silicone products.

Epiphora is the overflow of tears typically caused by obstruction or occlusion of the nasolacrimal duct. More attention is required to address this global health issue owing to the increase in air pollution. Implantation of a silicone stent is the preferred treatment for epiphora; however, introducing a silicone stent into a narrow duct with complex geometry is challenging as it requires guidance by a sharp metal needle. Additionally, silicone can cause adverse reactions such as biofilm formation and tear flow resistance due to its extreme hydrophobicity. To overcome these problems, in this study we developed a new type of biocompatible shape memory polymer (SMP) stent with elasticity capacity for self-expansion. First, SMPs in the form of x%poly(ε-caprolactone)-co-y%poly(glycidyl methacrylate) (x%PCL-y%PGMA) were synthesized via ring opening polymerization by varying the molar ratio of PCL (x%) and PGMA (y%). Second, the shape memory and mechanical properties were tuned by controlling the crosslinking degree and concentration of x%PCL-y%PGMA solution to produce a test type of SMP stent. Lastly, this 94%PCL-06%PGMA stent exhibited more standout critical functions in a series of in vitro and in vivo experiments such as a cell growth-supporting level of biocompatibility with nasal epithelial cells without significant inflammatory responses, better resistance to biofilm formation, and more efficient capacity to drain tear than the silicone control. Overall, 94%PCL-06%PGMA can be suggested as a superior alternative to the currently used materials for nasolacrimal stents. STATEMENT OF SIGNIFICANCE: Silicone intubation (stenting) has been widely used to treat nasolacrimal duct obstruction, however, it can cause adverse clinical effects such as bacterial infection; presents procedural challenges because of the curved nasolacrimal duct structure; and shows poor drainage efficiency stemming from the highly hydrophobic nature of silicone. In this work, we describe an innovative shape memory polymer (SMP) as a superior alternative to conventional silicone-based materials for nasolacrimal duct intubation. We demonstrate the clear advantages of the SMP over conventional silicone, including a much higher drainage capacity and superior resistance to bacterial infection.

Evaluation of the tear clearance rate by dacryoscintigraphy in patients with obstructive meibomian gland dysfunction.

PURPOSE: To measure tear clearance values in patients with meibomian gland dysfunction (MGD) with a dynamic nuclear medicine method, namely, dacryoscintigraphy (DSCI). METHODS: Twenty-four MGD patients and 24 healthy volunteers were examined. During DSCI one drop of a solution with 100 MBq/mL99mTc sodium pertechnetate was instilled with a micropipette into the lacrimal lake of both eyes. Measurements were performed according to a dynamic data acquisition protocol, which resulted in summed DSCI images. Data were also evaluated separately in special regions of interest (ROI), and consecutive time activity curves were created. Tear clearance (T½) values were calculated based on the activity curves. In addition, tear osmolarity measurements, tear breakup time (tBUT), and Schirmer I (STI) tests were performed prior to DSCI examination. RESULTS: The T½ values were 29.91 ± 11.61 min in MGD patients and 6.26 ± 1.5 min in healthy controls. Tear osmolarity parameters were 308 ± 9.41 mOsm/L and 288.9 ± 6.4 mOsm/L, tBUT values were 5.54 ± 2.73 s and 11.4 ± 2.7 s, while the STI test values were 6.17 ± 2.78 mm and 13.58 ± 3.8 mm, respectively. The differences were significant (p < 0.01) in all cases. CONCLUSIONS: Although the MGD patients' lacrimal drainage systems were patent their tear clearance values were significantly higher than those of healthy volunteers, which may be caused by decreased drainage of tears from the eyes towards the nasal cavity. The understanding of new features regarding the altered physico-chemical characteristics of MGD tears has been augmented by the results of this study.

Altered Surfactant Protein Expression in Primary Acquired Nasolacrimal Duct Obstruction.

PURPOSE: To investigate the presence and distribution patterns of 6 surfactant proteins in lacrimal drainage tissues of patients with primary acquired nasolacrimal duct (NLD) obstruction. METHODS: The presence and distribution of surfactant proteins (SP)-G and SP-H was first assessed in normal cadaveric lacrimal systems. The study was then performed in 10 samples of lacrimal sac and the respective NLDs obtained from patients suffering from primary acquired NLD obstruction who underwent either a dacryocystorhinostomy or a dacryocystectomy. The lacrimal sac samples were further divided into fundus and body, soon after their removal. Immunohistochemical labeling was performed for assessing the presence and distribution of SPs: SP-A, SP-B, SP-C, SP-D, SP-G/SFTA2, and SP-H/SFTA3. The results were then scored as positive or negative and the distribution pattern, if any, within the lacrimal sac and NLDs was assessed. Human lung tissues were used as controls. RESULTS: SP-H was demonstrated in the lining epithelia of the normal lacrimal drainage systems, whereas SP-G was uniformly negative. Immunohistochemical labeling revealed wide variations in the staining patterns of different SPs in different regions of the lacrimal sac and the NLD. SP-D and SP-G revealed uniformly negative immunoreactivity. Variable staining patterns were also noted between the superficial and basal layers of the lining epithelia. However, the goblet cells and intraepithelial mucous glands did not express any of the SPs. CONCLUSIONS: This study provides a proof of principle for the presence of SP-H and absence of SP-G in the normal lacrimal drainage systems. In cases of primary acquired nasolacrimal duct obstruction, there were alterations or loss of SP expression in the lining epithelia of the lacrimal sac and NLDs, reflecting their possible role in the etiopathogenesis of primary acquired nasolacrimal duct obstruction.In cases of primary-acquired nasolacrimal duct obstruction, the expression of multiple surfactant proteins was either deranged or lost in the lining epithelium of the lacrimal sac and nasolacrimal ducts.

Relationship between lacrimal sac size and duration of tearing in nasolacrimal duct obstruction.

OBJECTIVE: To analyze the relationship among the presence of lacrimal sac mucus retention, the vertical size of the lacrimal sac, and the duration of tearing symptom in patients with nasolacrimal duct obstruction (NLDO). DESIGN: Retrospective case series. PARTICIPANTS: We reviewed the medical records of 473 patients (664 eyes) who underwent external dacryocystorhinostomy for primary NLDO. METHODS: The information about the presence of lacrimal sac mucus retention and vertical size of the lacrimal sac lumen was collected intraoperatively. The vertical size of the lacrimal sac was classified into 3 groups: small (<5 mm), medium (5-10 mm), and large (>10 mm). The relationship between the lacrimal sac size, presence of mucus retention, and duration of tearing was analyzed. RESULTS: Of the 664 eyes, 138 had a small lacrimal sac, 199 had a medium lacrimal sac, and 327 had a large lacrimal sac. The distribution of the lacrimal sac size groups differed significantly between the eyes with (n = 245) and without (n = 419) mucus retention (p < 0.001). Among all the subjects of each lacrimal sac size group, there was no significant difference in the duration of symptoms (p = 0.176). However, in patients without mucus retention, the symptom duration in the small lacrimal sac group was significantly longer than that in the large lacrimal sac group (p = 0.017). CONCLUSIONS: In cases with mucus retention, a small lacrimal sac is rare. In cases without mucus retention, the duration of tearing symptom was significantly longer in small lacrimal sac group.

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.

Biopsy of recurrent nasolacrimal duct obstruction using sheath-guided dacryoendoscopy.

PURPOSE: The purpose of this article is to present a novel technique, as well the histopathological findings, of dacryoendoscopic guided nasolacrimal duct (NLD) biopsy for recurrent nasolacrimal duct obstruction (NLDO). METHODS: This study involved subjects with recurrent NLDO. Direct endoscopic probing or sheath-guided endoscopic probing was used for the initial intubation in all treated eyes, and the stent had been removed at between 2 and 11 months (mean 3.5 months) post-intubation with dacryoendoscopic confirmation of patency and mucosal regeneration. Biopsy specimens were obtained by scraping the recurrent lesion by sheath advancement. Histopathological examination and immunohistochemical (IHC) staining were performed. RESULTS: In five patients (two males and three females, mean age: 71.2 ± 5.6 years [range: 61-78 years]) with recurrent NLDO, biopsy specimens were obtained from six ducts of six eyes, and stratified epithelium and a mixed inflammatory cell infiltrates were identified. IHC staining was positive for cytokeratin (CK)4 and CK13, and negative for paired box protein Pax-6. CONCLUSIONS: This novel technique enabled a minimally invasive biopsy of the NLD to be obtained, and IHC staining indicated the presence of mucus epithelium, thus suggesting squamous metaplasia of the usual respiratory epithelium which likely occurs secondary to chronic inflammation.

Soluble glycoproteins of the lacrimal sac: role in defense with special reference to prolactin-inducible protein (PIP).

Purpose: Glycoproteins play an important role in human mucosal defenses and immunity-related cell-to-cell interactions. The aim of the present study is to investigate the presence and patterns of lacrimal sac glycoproteins involved in defense mechanisms with a special reference to prolactin-inducible protein (PIP). Methods: The study was performed on healthy lacrimal sacs obtained from exenteration samples immediately after surgery and frozen at -80 degrees for subsequent analysis. Four lectins namely Concanavalin A (Con A), Dolichos lablab lectin (DLL), Wheat Germ agglutinin (WGA), and Momordica charantia lectin (MCL) were purified by affinity chromatography. Soluble proteins extract of the lacrimal sac was subjected to chromatography on lectin-affigel columns. Eluted samples from each of the lectin coupled-affigels were analyzed by 10% SDS-PAGE under reducing conditions and the protein bands were visualized using Coomassie blue stain. The protein gel bands were further subjected to mass spectrometry for glycoprotein analysis. Results: Mass spectrometry identified several glycoproteins from the lacrimal sac extracts, with known roles in defense mechanisms. The number of such glycoproteins identified were 9 each from Con A and DLL-I affinity eluted gel bands and 8 and 14 from MCL and WGA affinity eluted gel bands, respectively. Interestingly, PIP was detected in significant proportions in all the eluted gel bands with WGA showing the highest expression. Conclusions: This study is the first step towards the lacrimal sac glycoprotein profiling. PIP could be a major lead for further work on the etiopathogenesis of lacrimal drainage obstructions.

Clinical features and treatment outcomes of patients with tearing after chemotherapy.

PURPOSE: To evaluate the clinical features and treatment outcomes of patients complaining of tearing after receiving chemotherapy. METHODS: The clinical records of patients who complained of tearing between August 2014 and February 2016, and underwent or were undergoing chemotherapy were retrospectively reviewed. Clinical measurements were as follows: LipiView® interferometer (lipid layer thickness and meibography), lacrimal drainage examinations (syringing), and outcomes at 6 months after treatment. RESULTS: This study included 34 eyes of 17 patients with a mean age of 62.4 ± 14.82 years. The mean follow-up period was 9.6 months. On syringing, 10 eyes (29.4%) showed total regurgitation, 19 eyes (55.9%) showed partial regurgitation, and 5 eyes (14.7%) showed no regurgitation. On LipiView®, mean lipid layer thickness was 34.5 nm (range, 20-89 nm). Mean meiboscore was 2.15 ± 0.86 in upper eyelid and 2.53 ± 0.79 in lower eyelid. Patients were treated with silicon tube intubation (STI) (10 eyes, 29.4%), dacryocystorhinostomy (DCR) (4 eyes, 17.6%), conjunctivodacryocystorhinostomy (CDCR) (8 eyes, 11.8%), DCR combined with CDCR (1 eyes, 8.8%), and conservative care (11 eyes, 32.4%). Mean time interval from onset of tearing to first clinic visit was 1.4 months in the conservative care group, 2.9 months in the STI and DCR groups, and 6.0 months in the CDCR group. CONCLUSION: Because of the high incidence of accompanying meibomian gland loss in cases of lacrimal drainage system (LDS) obstruction, reflex tearing by mebibomian gland dysfunction should also be considered for proper management of tearing. Early recognition and management of LDS stenosis could result in patients undergoing surgery with a lower burden.

Evaluation of Tear Film Lipid Layer Thickness Measurements Obtained Using an Ocular Surface Interferometer in Nasolacrimal Duct Obstruction Patients.

PURPOSE: To compare the tear film lipid layer thickness (LLT) between patients with incomplete nasolacrimal duct obstruction (NLDO) and normal controls and to analyze the changes in tear film LLT and blinking pattern after silicone tube intubation in NLDO patients. METHODS: We reviewed the medical records of 68 eyes in 52 incomplete NLDO patients who underwent silicone tube intubation from January 2017 to July 2017. The LLT, blinking pattern, and Meibomian gland image were measured with the LipiView II ocular surface interferometer. The Meibomian gland drop-out ratio was measured using the polygon selection tool in the Image J program. Tear meniscus height, which is the other lacrimal indicator, was assessed with spectral-domain optical coherence tomography. RESULTS: Tear meniscus height was significantly decreased after silicone tube intubation (p < 0.01). Preoperative minimum, maximum, and average LLT values were 62.4 ± 24.0, 86.7 ± 17.9, and 71.7 ± 23.3 nm, respectively. Significant changes in the minimum, maximum, and average LLT (74.8 ± 23.6, 98.8 ± 11.0, and 91.6 ± 16.1 nm, respectively) were observed after silicone tube intubation (p < 0.001, p = 0.001, and p < 0.001). The partial blinking/total blinking ratio in 20 seconds and the Meibomian gland drop-out ratio showed no significant change after silicone tube intubation. CONCLUSIONS: Overall, the LLT was increased after silicone tube intubation. Silicone tube intubation may be helpful in maintaining LLT with a normalized of amount of tears.

The role of "after washing imaging" in evaluation of tear drainage system by dacryoscintigraphy.

BACKGROUND: The aim of this study was to evaluate the efficacy of "after washing" imaging in interpretation of dacryoscintigraphy as a functional imaging technique used in evaluation of tearing problems. MATERIALS AND METHODS: 300 nasolacrimal systems were studied. 100 µCi of technetium-99m sodium pertechnetate as drops of activity (10 µL) were placed into the inferior fornix of each eye. Dynamic images were obtained for 15 minutes in the sitting position. "After washing" phase was done by placing a drop (10 µL) of normal saline in each eye and external ocular massage for an additional 10 minutes. The imaging patterns for each eye in the first dynamic phase and after washing phase were recorded, separately. RESULTS: First dynamic phase demonstrated a sensitivity of 97.4% and specificity of 22.6%. After washing phase showed a sensitivity of 91.2% and specificity 75.5%. After washing test, the obstruction pattern changed to "patent nasolacrimal duct" or "further progression" of the radiotracer to the nasolacrimal duct in the 25.1% and 24.4% of the nasolacrimal systems, respectively. CONCLUSIONS: After washing imaging is a useful method in dacryoscintigraphy which can improve the specificity of scan for diagnosis of lacrimal duct obstruction. It can also improve the localization of obstruction level in the lacrimal systems.

Electron microscopic features of the lacrimal sac mucopeptide concretions.

PURPOSE: The aim of this study was to examine the ultrastructural features of the mucopeptide concretions obtained from the lacrimal sac. METHODS: Mucopeptide concretions obtained from the lacrimal sacs of 10 patients during a dacryocystorhinostomy were immediately fixed for electron microscopic analysis. The surfaces were studied separately and longitudinal and transverse ultra-thin sections were obtained at different levels and all were studied using the standard protocols of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Mucopeptide concretions based on their extent take the shape of the lacrimal sac and nasolacrimal duct. The external surfaces and cut sections show mostly areas of homogenous deposits with occasional intervening heterogenic areas. Two distinct types of craters were noted, mostly in the heterogeneous areas. The core of the concretions was made up of extensive networks of fibril like tangles filled predominantly with granular material and red blood cells with occasional presence of granulocytes and epithelial cells. Numerous vacuoles and fissures appear to be more of artifacts than any metabolic process. No organic fibers of fungal filaments were noted within the concretions. There was no evidence of any bacterial biofilms other than few focal areas of scattered bacteria. Possible events in the development of mucopeptide concretions have been hypothesized based on the ultrastructural findings. CONCLUSION: Ultrastructural features of mucopeptide concretions from the lacrimal sac help in better understanding of their etiopathogenesis and tissue interactions. Further exploration of different stages of a concretion is needed to understand the potential factors that trigger its genesis and evolution.

Immunostaining of Immunoglobulin G4 in the Lacrimal Sac.

PURPOSE: To immunohistochemically examine the lacrimal sac walls harvested during dacryocystorhinostomy using an immunostain for immunoglobulin G4 (IgG4). METHODS: Forty-four lacrimal sac walls were evaluated. We determined "intensively positive," "sparsely positive," or "negative" staining when the specimens showed IgG4-positive lymphoplasmacytic staining with or without >50 IgG4-positive cells/high-power field, or the absence of stained IgG4-positive cells. RESULTS: Intensively positive, sparsely positive, or negative staining was observed in 8 (18.2%), 14 (31.8%), and 22 specimens (50.0%), respectively. Stained cells infiltrated the subepithelial layer in all specimens with positive staining. Four of the 8 specimens demonstrated partial epithelial denudation with loss of goblet cells. CONCLUSIONS: IgG4-positive lymphoplasmacytic infiltration was observed in the subepithelial layer in specimens with intensively positive staining, of which some showed a partially denuded epithelium with loss of goblet cells. These may lead to narrowing of the lacrimal sac lumen and adhesions of the sac walls.

Qualitative Hormonal Profiling of the Lacrimal Drainage System: Potential Insights into the Etiopathogenesis of Primary Acquired Nasolacrimal Duct Obstruction.

PURPOSE: To investigate the presence and distribution patterns of hormone receptors in the lacrimal drainage system in normal and diseased states. METHODS: The study was performed on cadaveric and clinical samples of the lacrimal drainage system. Immunohistochemical labeling was performed for assessing the presence and distribution of receptors of estrogen alpha, estrogen beta, aromatase (CYP19), testosterone, progesterone, oxytocin, prolactin, and somatostatins 1 to 5 (SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5). The immunohistochemistry stains were scored as positive or negative, and the distribution patterns in the canaliculus, lacrimal sac, and nasolacrimal duct were assessed. RESULTS: There was a strong expression of estrogen alpha, estrogen beta, and oxytocin, but this showed variations in distribution patterns. Testosterone and progesterone expressions were more localized to the basement membrane of the epithelium in postmenopausal females. While SSTR2 and SSTR4 expressed only on the villus surfaces of superficial epithelial cells; oxytocin, aromatase, and prolactin additionally expressed in the subepithelial lamina propria and submucosal glands. Diseased samples from primary acquired nasolacrimal duct obstruction showed dramatic reduction or absence of the receptor expression patterns of all the hormones with the exception of epithelial immunoreactivity with prolactin. CONCLUSIONS: This study provides a proof of principle for the presence of multiple hormone receptors and hypothesizes their possible links in the etiopathogenesis of primary acquired nasolacrimal duct obstructions.