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.

CHARGE syndrome without colobomas: Ophthalmic findings.

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients-clinically confirmed diagnosis with positive CHD7 mutation-seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion in this study was absence of any form of a coloboma in either eye. In our cohort, all patients had a positive CHD7 mutation, in addition to a clinical diagnosis. 19.4% (13/67) of CHARGE patients did not have a coloboma in either eye. 69.2% (9/13) had strabismus, 76.9% (10/13) had a refractive error that warranted refractive correction, 23.1% (3/13) had amblyopia, 38.5% (5/13) had nasolacrimal duct obstruction, 30.8% (4/13) had dry eye syndrome and exposure keratopathy, 15.4% (2/13) had ptosis, 15.4% (2/13) had blepharitis, 15.4% (2/13) had Cortical Visual Impairment, 7.7% (1/13) of patients had optic nerve drusen, 7.7% (1/13) had Marcus Gunn Jaw Winking, and 7.7% (1/13) with an eyelid nevus. There are numerous ophthalmic findings in individuals with CHARGE Syndrome without colobomas. No study to date has evaluated the ophthalmic findings in CHD7 positive CHARGE patients without colobomas. These findings need to be assessed and treated to ensure optimal vision in the CHARGE patient population. Absence of coloboma does not rule out a diagnosis of CHARGE syndrome, and if there is a clinical suspicion, clinical confirmation then genetic testing would be warranted.

Isolation and characterization of abundantly-expressed cDNAs from the Harderian gland of the garter snake (Thamnophis sirtalis: Colubridae).

The Harderian gland (HG) is an orbital structure whose proteinaceous secretions pass through the nasolacrimal duct to the vomeronasal organ (VNO). Though these three structures occur in many tetrapod vertebrates, the garter snake (Thamnophis sirtalis) is one of the few vertebrates in which the passage of the proteinaceous secretions have been experimentally shown. Secreted proteins from the HG may function as transporters for chemical signals to the VNO epithelium. To investigate the proteins being produced by the HG of the garter snake, cDNA libraries were constructed from HG mRNA, and several individual cDNAs were analyzed by sequencing, RT-qPCR, and PCR on genomic DNA. Two of the three cDNAs that were characterized are abundantly expressed only in the Harderian gland and contain putative signal sequences for secretion, which makes them candidates for transporter proteins secreted from the HG. One is a member of the large lipocalin family of proteins, based on its similarity to other members of that protein family. Many lipocalins are binding/carrier proteins for a variety of ligands. The other is a family of proteins, with five members identified so far, all of unknown structure and function and present in the garter snake genome but not in other squamate genomes.

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.

Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

BACKGROUND: The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. RESULTS: Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. CONCLUSIONS: NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

Expression of Surfactant Proteins in the Human Canaliculus: Evidence and Potential Insights Into the Tear Flow Dynamics.

PURPOSE: To investigate the presence and distribution patterns of 6 surfactant proteins (SPs) in the human lacrimal canaliculus. METHODS: The study was performed on fresh frozen cadaveric samples of canaliculi. Immunohistochemical labeling was performed for assessing the presence and distribution of SP: SP-A, SP-B, SP-C, SP-D, SP-G/SFTA2, and SP-H/SFTA3. Immunofluorescence double staining was performed using the respective fluorescein-conjugated antibodies and the results were scored as positive or negative and the distribution pattern within the canalicular system was assessed. Western blot analysis was performed on the protein content which was resolved by reducing 15% sodium dodecyl sulfate-polyacrylamide electrophoresis and bands were studied following staining with primary and secondary antibodies. Human lung tissues were used as controls. RESULTS: Fluorescence double staining with 4,6-diamidino 2-pheynlindole and SPs showed strong immunostaining for SP-A, SP-B, SP-C, SP-D, and SP-H/SFTA3. The positive immunofluorescence was noticed across all the layers of the epithelium but not the subepithelial structures. The expression was noted on the surfaces and superficial cytoplasm of the superficial and deep epithelial cells. There was no expression of SP-G/SFTA2 across the canalicular system. Western blot analysis of the proteins confirmed and concurred with the immunofluorescence findings. CONCLUSIONS: This study provides a proof of principle for the presence of SPs known from lungs in the canalicular system and hypothesizes their possible functions and also their potential role in the tear flow dynamics between the ocular surface and the lacrimal drainage system.

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.

Histopathology, Immunohistochemistry, and Electron Microscopic features of a Dacryocystorhinostomy Ostium Cicatrix.

PURPOSE: The aim of this study is to report the histopathological, Immunohistochemical, and ultrastructural features of a dacryocystorhinostomy ostium cicatrix. METHODS: A prospective histopathological study was performed in a tertiary eye care setting. Scarred nasal mucosal tissues obtained during endoscopic revisions of 10 previously failed dacryocystorhinostomies secondary to complete cicatricial closure of the ostia were studied. The tissue specimens were analyzed using hematoxylin and eosin, periodic acid-Schiff staining. Special stains used include Masson's trichrome and Alizarin red. Immunohistochemistry was performed using vimentin, smooth muscle actin, CD3, CD5, and CD20. Specimens were processed for ultrastructural analysis as per standard protocols for transmission electron microscopy. RESULTS: The respiratory epithelial regeneration was noted to be complete. Irregular laying of deeply eosinophilic and hyalinized collagen with intervening fibroblasts was noted. Focal areas of new bone formation were seen within the cicatricial tissue with osteocytes and ongoing osteoblastic rimming. The infiltrates were mixture of both T and B lymphocytes and were positive for CD3, CD5, and CD20 immunostaining. Electron microscopy showed disorganized collagen fibrils with numerous fibroblasts and mononuclear inflammatory infiltrate. Amorphous bony osteoid within a fibrillar background with metabolically active osteoblasts showed a vesicular cytoplasm, hyperplastic proliferating mitochondria, large Golgi apparatus, and dense endoplasmic reticulum. CONCLUSION: There is new bone formation within the dense connective tissues of a dacryocystorhinostomy cicatrix. This study may provide useful inputs for further basic science studies aimed at better understanding of wound healing in failed dacryocystorhinostomy.

Primary Mucoepidermoid Carcinoma of the Lacrimal Sac -  a Case Report and Literature Review.

BACKGROUND: Lacrimal sac tumors are very rare and are often missed because patients present with features consistent with chronic dacryocystitis. Squamous cell carcinoma is the common-est lacrimal sac malignancy. Although primary mucoepidermoid carcinomas of the lacrimal sac are rare, they are locally aggressive. Furthermore, their proximity to vital structures and the skull base makes them potentially life-threatening. Multidisciplinary management is required, and wide excision followed by chemoradiation is the recommended treatment. CASE: Here, we report a 65-year-old male who presented with watering eyes and a mass in the region of the medial canthus. A dia-gnosis of primary mucoepidermoid carcinoma of the lacrimal sac was made, and the case was managed successfully with radical surgery and reconstruction. The tumor was resected using the extended Lynch-Howarth incision and the resulting defect was reconstructed using a forehead flap. Histopathological examination of the excised specimen revealed mucoepidermoid carcinoma. Immunohistochemical analysis revealed that the speci-men was positive for epithelial growth factor receptor and Ki-67 protein. The patient was referred for post-operative chemoradiation. The literature is reviewed and pathological features, including immunohistochemistry are discussed. CONCLUSION: Primary mucoepidermoid carcinoma of the lacrimal sac is a rare, locally aggressive tumor that is often mistaken for dacryocystitis. The treatment of choice is radical surgery followed by chemoradiation. KEY WORDS: lacrimal sac -  mucoepidermoid carcinoma -  epithelial growth factor receptor -  Ki-67 protein.

Powered endoscopic dacryocystorhinostomy: a decade of experience.

PURPOSE: To report a decade long experience with powered endoscopic dacryocystorhinostomy (DCR). METHODS: A retrospective review of all consecutive patients undergoing powered endoscopic DCR was performed at this institution over a period of 11 years from 2002 to 2013. All patients completed a minimum of 3 months follow up following stent removal. Patient records were reviewed for demographic data, clinical and surgical profiles, adjunctive procedures, complications, and success rates at the last follow up. Anatomical success was defined as patent ostium on irrigation and functional success as free flow of dye into ostium on functional endoscopic dye test and resolution of epiphora. RESULTS: Two hundred eighty-three powered endoscopic DCRs were performed on 214 patients. The mean age at surgery was 59.5 years (range, 3-95 years). All patients presented with epiphora. A total of 91.6% patients (196/214) had a primary DCR and 8.4% (18/214) had a revision DCR. In all, 50.4% patients (108/214) underwent adjunctive endonasal procedures. The mean follow up was 17.1 months (range, 3-103 months). At the last follow up, the final anatomical success was achieved in 96.9% cases of primary DCRs and 91.3% cases of revision DCRs. Functional success was achieved in 93% cases of primary DCRs and 86.9% cases of revision DCRs. CONCLUSIONS: Powered endoscopic DCR is a safe procedure and offers excellent results both in primary and revision DCRs. The threshold to perform adjunctive endonasal procedures should be very low when indicated.

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.

Involvement of Laryngopharyngeal Reflux in Ocular Diseases: A State-of-the-Art Review.

BACKGROUND: Laryngopharyngeal reflux-associated symptoms embrace a wide variety of head and neck manifestations. Its participation in eye disorders has recently been postulated, and there is currently no consensus in this regard. The aim of this manuscript is to review the role of reflux in the development of ocular signs and symptoms, and its physio-pathological mechanisms. METHODS: A systematic approach based on the preferred reporting Items for a systematic review and meta-analysis checklist with a modified population, intervention, comparison, and outcome framework was used to structure the review process of studies that evaluated the possible association, with clear diagnostic methods, of laryngopharyngeal reflux and ocular signs and symptoms. Search was conducted in different indexed databases (PubMed/MEDLINE, the Cochrane Library, Scielo and Web of Science) and through the meta-searcher Trip Database with the keywords: reflux, laryngitis, laryngopharyngeal, gastroesophageal, ocular, eye, symptoms, signs, conjunctivitis, keratitis, dacryocystitis, dry eye. RESULTS: Seven studies met the inclusion criteria, in which the primary acquired nasolacrimal duct obstruction and the ocular surface disease were evaluated. The local increase of eye pepsin concentration (>2.5 ng/mL) may affect ocular surface though its direct proteolytic activity and the local expression of proinflammatory cytokines. The H. Pylori, with a similar mechanism to reach the lacrimonasal duct, would be associated with the release of proinflammatory and vasoactive substances that would lead to a mucosa injury and chronic inflammation. Ocular Surface Disease Index seems to correlate directly with the reflux severity, with cut-off of 41.67 score as predictor for disease. DISCUSSION: The role of laryngopharyngeal reflux in the development of ocular disorders has not yet been demonstrated and data are limited and heterogeneous. It seems theoretically conceivable that pepsin may reach lachrymal duct area through hypopharyngeal-nasal gaseous reflux events. Future studies using objective testing for diagnosis and pepsin detection into the tear and nasal mucosa are needed in order to explore this potential relationship.

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.

Obstruction of the Tear Drainage Altered Lacrimal Gland Structure and Function.

Purpose: Orbital glands and drainage conduits are two distinct entities that constitute the lacrimal apparatus system, the malfunction of which leads to a range of ocular surface disorders. Despite the close functional relationship, how the two parts interact under pathophysiological conditions has not been directly tested. The study aims to investigate the lacrimal gland (LG) structural and functional changes upon the drainage system obstruction, thus, testing their function link. Methods: Dacryocystectomy was performed in C57BL/6 mice to create a surgical model for tear duct (TD) obstruction (STDOB). Prickle1 mutant line with congenital nasolacrimal duct dysplasia serves as a genetic model for TD obstruction (GTDOB). Alterations of the LG and the ocular surface in tear duct obstruction mice were examined. Results: STDOB and GTDOB mice showed similar ocular surface phenotypes, including epiphora, corneal epithelial defects, and conjunctival goblet cell abnormalities. At the molecular and cellular levels, aberrant secretory vesicle fusion of the LG acinar cells was observed with altered expression and localization of Rab3d, Vamp8, and Snap23, which function in membrane fusion. LG secretion was also altered in that lactoferrin, lipocalin2, and lysozyme expression were increased in both LG and tears. Furthermore, STDOB and GTDOB mice exhibited similar LG transcription profiles. Conclusions: Physical obstruction of tear drainage in STDOB or GTDOB mice leads to LG dysfunction, suggesting a long-distance interaction between the tear drainage conduits and the LG. We propose that various components of the lacrimal apparatus should be considered an integral unit in diagnosing and treating ocular surface diseases.

High-risk HPV-related Squamous Cell Carcinoma in the Conjunctiva and Lacrimal sac: Clinicopathologic Characteristics and Diagnostic Utility of p16 and Rb Immunohistochemistry.

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

Factors associated with outcome of endonasal dacryocystorhinostomy.

PURPOSE: To identify factors associated with outcome of endonasal dacryocystorhinostomy. METHODS: One hundred thirty-four cases of endonasal dacryocystorhinostomy in 111 patients performed for primary acquired nasolacrimal duct obstruction by a single surgeon between March 12, 2002 and November 10, 2008 were included in a retrospective, noncomparative case series. Variables assessed during the surgery included intranasal view, difficulty of bone removal, size of the lacrimal sac, presence of lacrimal sac stones, orbital fat prolapse and degree of bleeding. Successful outcome was defined as patency to lacrimal irrigation at final follow up. RESULTS: One hundred twenty-one of the 134 cases (90%) were patent to irrigation at final follow up (mean 8.8 ± 8.6 months). A small lacrimal sac opening intraoperatively was associated with higher risk of failure (odds ratio [95% confidence interval] of 5.7 [1.6, 20] [p = 0.0072]). Orbital fat prolapse had a trend toward higher risk of failure that approached statistical significance (odds ratio [95% confidence interval] of 5.3 [0.87, 32] [p = 0.0698]). A narrow intranasal view, difficult bony opening, lacrimal sac stones, and bleeding were not associated with outcome. CONCLUSIONS: A small lacrimal sac opening intraoperatively was associated with failure of endonasal dacryocystorhinostomy.

Evaluation of lacrimal tear drainage mechanism using dynamic fluoroscopic dacryocystography.

PURPOSE: To evaluate the dynamic change of the canaliculus and the lacrimal sac during blinking using fluoroscopic dacryocystography. METHODS: Sixteen patients presenting with unilateral epiphora were enrolled in the study. Fluoroscopic dacryocystography was performed in both eyes, and sequential images of the lacrimal drainage system were acquired during blinking. On examination of the contralateral asymptomatic side, the length of the lower canaliculus and the width of the superior and inferior portions of the lacrimal sac were measured and compared between eyelid closure and opening. RESULTS: The length of the lower canaliculus decreased with eyelid closure in 13 of 16 patients, and the change was statistically significant (p = 0.006, Wilcoxon signed rank test). The width of the superior portion of the lacrimal sac increased with eyelid closure (p = 0.033), but the width of the inferior part did not change significantly (p = 0.679). CONCLUSIONS: With eyelid closure, the canalicular system contracts, and the superior portion of the lacrimal sac dilates; these may be important parts of the active lacrimal pump mechanism. These findings suggested that the canalicular system and the superior portion of the lacrimal sac play key roles in active tear drainage pump.

A modified Jones test: lacrimal scintigram correlation.

PURPOSE: To determine the correlation between lacrimal scintigraphy and a modified Jones primary dye drainage test combined with the fluorescein dye disappearance test (DDT) and Jones secondary dye test, in diagnosing the cause of epiphora. METHODS: A prospective, consecutive clinical trial was conducted. All patients presenting with epiphora were considered, but those with trichiasis, corneal irritation, lower eyelid ectropion, Bell palsy, or previous lacrimal surgery were excluded. A cohort of 39 patients (65 eyes) underwent the fluorescein DDT and the senior author's (R.B.) modified Jones primary dye drainage test (Jones dye test 1 [JDT1]). For this test, an entire fluorescein 2% Minim dose was instilled in the 2 eyes, and the patient was then asked to gently blow each nostril separately in a white tissue; the degree of fluorescein staining was noted. If there was no fluorescein staining of the tissue (negative JDT1), a traditional Jones secondary dye test (Jones dye test 2) was also performed. All patients except for those testing strongly positive on modified testing or with negative DDT and JDT1 and nil drainage from the nose in Jones dye test 2, indicating anatomical obstruction, were referred for lacrimal scintigraphy. RESULTS: In total, 59 of 65 eyes (91%) showed a positive correlation between the diagnosis arrived at after dye testing using the modified primary dye test and diagnosis on lacrimal scintigraphy. The interrater reliability for the raters was found to be κ = 0.770 and 95% confidence interval = 0.594-0.945. The strength of agreement is considered to be "good." CONCLUSIONS: The authors found that in the presence of patent lacrimal drainage system dysfunction, modified Jones primary dye test, combined with the fluorescein DDT and Jones secondary dye test, correlated strongly with lacrimal scintigraphy.