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A modified endoscopic dacryocystorhinostomy technique using a clubhead-shaped nasal flap combined with a posteriorly hinged lacrimal flap was designed for tension-free anastomosis with the surrounding mucoperiosteum. This technique showed satisfactory outcomes that facilitated the maintenance of the rhinostomy in eight cases with nasolacrimal duct obstruction. Laryngoscope, 132:2314-2318, 2022.

Epidermal growth factor (EGF) and hepatocyte growth factor (HGF) regulate the growth and morphogenesis of various exocrine glands with branched morphologies. Their roles in lacrimal gland (LG) development remain unknown, but fibroblast growth factor (FGF) 10 is crucial for early LG organogenesis. To clarify the roles of EGF, HGF, and FGF10 in LG development, LG epithelial cells were isolated from late-embryonic and neonatal mice; cultured; and treated with EGF, HGF, or FGF10 and their respective receptor tyrosine kinase (RTK) inhibitors AG1478, PHA665752, or SU5402. EGF and HGF increased the number of viable cells by enhancing DNA synthesis, FGF10 and SU5402 showed no such effect, and RTK inhibitors exhibited the opposite effect. EGF and HGF receptors were immunostained in cultured late-embryonic LG epithelial cells and terminal LG acini from late embryos and adult mice. HGF was detected in neonatal LG epithelial cell culture supernatants by western blotting. In the absence of EGF and HGF RTK inhibitors, growth factor addition increased the number of viable cells and suppressed cell death. However, when one RTK was inhibited and a growth factor targeting an intact RTK was added, the number of dead cells increased as the number of viable cells increased. No cells survived when both RTKs were inhibited. In explant cultures of LGs from embryos, AG1478 or PHA665752 decreased the number of Ki67-positive proliferating epithelial cells in terminal acini. Thus, EGF and HGF may function in a cooperative autocrine manner, supporting cell proliferation and survival during LG development in late-embryonic and neonatal mice.

This study sought to describe the anatomical characteristics of the nasolacrimal duct of Persian cats as observed by computed tomographic dacryocystography.Ten cats weighing 3-6 kg (three live cats and seven cadaveric specimens).The animals were submitted to bilateral computed tomographic dacryocystography, totaling 20 nasolacrimal ducts. Dorsal, sagittal, and transverse planes were studied. Two additional skulls were also dissected following latex injection into the nasolacrimal duct. The length and width of the nasolacrimal duct and lacrimal canaliculi, and the distance between the nasolacrimal duct and the root of the upper canine tooth at the point of closest proximity were measured.The nasolacrimal duct followed a convoluted course, particularly in the middle and rostral portions. Duct stenosis (width reduction equal to or75%) and dilations (width increase equal to or50%) were also detected, particularly in the rostral portion. Nasolacrimal duct length and width ranged from 1.3 to 1.5 cm and 1.5 to 2.3 mm, respectively. Mean lacrimal canaliculus length and width corresponded to 3.1 mm and 0.4 mm, respectively. Mean distance from the nasolacrimal duct to the canine tooth was 2.4 mm. The root of this tooth interfered with the course of the nasolacrimal duct.This study provided anatomical information for clinical assessment of the nasolacrimal drainage system in Persian cats.

Objective To confirm the feasibility of visualizing upper and lower proximal lacrimal canaliculi (LC) using spectral-domain optical coherence tomography (SD-OCT). Animals studied Eight eyes of four normal Beagle dogs. Procedures To obtain an upper proximal LC image, the head was turned in the opposite direction to the eye being imaged, and the medial part of the upper eyelid was everted to expose the LC. To obtain a lower LC image, the lower eyelid was everted just below the punctum. Using "angle mode", the scan line was placed parallel on the long axis of the LC. The inlet LC width (LCW) was measured. Artificial tears (AT) were instilled, and LCW was compared before and after AT instillation. Additionally, the return time to the initial LCW inlet width was recorded. Results Before AT instillation, there was a significant difference between the mean upper and lower LCW (91.8 ± 3.2 µm and 110.1 ± 8.4 µm, respectively). After AT instillation, the mean upper and lower LCW were 236.9 ± 27.7 µm and 238.4 ± 30.4 µm, respectively. Significant differences in the LCW before and after AT instillation in both the upper and lower LCWs were observed. The mean return time of the upper and lower LCW to their initial widths after AT instillation was within 4 min. Conclusions Spectral-domain optical coherence tomography was an effective method for providing high-resolution images of the upper and lower proximal LC. This method enables observation of LC changes after instillation of eyedrops in veterinary clinical practice.

OBJECTIVE/HYPOTHESIS This study describes a multicentric experience with the use of prelacrimal approach (PLA), focusing on preoperative radiological parameters potentially associated with surgical outcomes and postoperative morbidity. STUDY DESIGN Retrospective case-series. METHODS A retrospective review of patients undergoing PLA in three European referral centers was performed. The post-operative morbidity was analyzed in relation to two radiological parameters: width of prelacrimal recess (WPR) and internal angle of pyriform notch (APN). RESULTS The study included 28 patients affected by Schneiderian papilloma (20 cases), inflammatory disease (6 cases), schwannoma (1 case), and osteoma (1 case). The most reported sequela was paresthesia of ipsilateral anterior superior alveolar process (25% of the cases). An association between post-operative morbidity and APN was observed (P = .047). CONCLUSIONS Preoperative radiological evaluation of WPR is crucial in understanding the feasibility of the approach, while APN measurement may predict postoperative morbidity, which is paramount in the patients' counseling. LEVEL OF EVIDENCE 4 case-series Laryngoscope, 131:1715-1721, 2021.

OBJECTIVES/HYPOTHESIS Although vidian neurectomy (VN) is associated with decreased lacrimation, its impact on dry eye quality-of-life is not well-defined. Endoscopic endonasal transpterygoid approaches (EETA) may require vidian nerve sacrifice. STUDY DESIGN A prospective cohort trial. METHODS A prospective trial evaluating VN during EETA on lacrimation by phenol red thread testing and dry eye severity by the five-item Dry Eye Questionnaire (DEQ-5) was performed. Preservation of the contralateral vidian nerve allowed comparison between the eye subjected to VN and the control eye postoperatively. RESULTS Twenty-one subjects were enrolled with no preoperative difference in lacrimation between eyes (P = .617) and overall mild dry eye severity. Although the control eye had no difference in lacrimation pre- and postoperatively, decreased tearing was noted in the VN eye at 1 month (20.8 mm vs. 15.8 mm, P = .015) and at 3 months (23.2 mm vs. 15.8 mm, P = .0051) postoperatively. Overall, no difference was noted in the DEQ-5 score for dry eye severity between the pre- and postoperative measures. However, six patients were noted to have moderate to severe dry eye severity postoperatively and five of these six had decreased lacrimation (

Lipids secreted by the meibomian glands (MGs) of the eyelids are essential to the protection of the eye’s surface. An altered meibum composition represents the primary cause of evaporative dry eye disease (DED). Despite the critical importance of the meibum, its biosynthetic pathways and the roles of individual lipid components remain understudied. Here, we report that the genetic deletion of Acyl-CoA:wax alcohol acyltransferase 2 (AWAT2) causes the obstruction of MGs and symptoms of evaporative DED in mice. The lipid composition of the meibum isolated from Awat2(−/−) mice revealed the absence of wax esters, which was accompanied by a compensatory overproduction of cholesteryl esters. The resulting increased viscosity of meibum led to the dilation of the meibomian ducts, and the progressive degeneration of the MGs. Overall, we provide evidence for the main physiological role of AWAT2 and establish Awat2(−/−) mice as a model for DED syndrome that can be used in studies on tear film-oriented therapies.

Background: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described. Purpose: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED. Methods: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated. Findings: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development. Conclusion: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED. This research was partly funded by NFR 271555 grant by the Norwegian Research Council, through the Medical Student Research Program. D.A. Dartt was supported by grants from the US NIH: R01 EY019470, R01 EY029789 and R01 EY021292.

Importance This study introduces a new technique in the assessment of nasolacrimal drainage with magnetic resonance imaging. Background To describe a new dynamic magnetic resonance dacryocystography (MRDCG) protocol and report normative findings on asymptomatic lacrimal drainage systems. Design A prospective observational study at the Royal Adelaide Hospital. Participants Seventeen patients with unilateral epiphora were prospectively recruited. Methods Patients underwent dynamic MRDCG. The time-resolved angiography with interleaved stochastic trajectories (TWIST) sequence was used to visualise contrast flow through the lacrimal drainage system. Main outcome measures Tear transit times and anatomical dimensions were measured. Results Dynamic MRDCG with TWIST sequence reliably demonstrated contrast flow. Tear transit times and anatomical dimensions were comparable to previously reported values in other imaging modalities. Conclusions and relevance Dynamic MRDCG provides good structural and temporal resolution to the assessment of lacrimal outflow obstructions. The physiological nature of this modality allows potential assessment for functional obstruction and future research on tear flow assessment.

OBJECTIVE: To provide a comprehensive anatomical description of the normal equine nasolacrimal duct using magnetic resonance imaging, and to develop a practical protocol for performing magnetic resonance dacryocystography (MRD) in horses. ANIMAL STUDIED: The heads of ten fresh horse cadavers with no history of sinonasal or ophthalmologic disorders were used for this study. PROCEDURE: An MRD technique was developed in this study, which consisted of two parts. In the first part, olive oil and gadolinium were compared as contrast medium, using five horses. Two concentrations of gadolinium were used: 0.25 mmol/mL and 0.5 mmol/mL. In the second part, the influence of different head recumbencies using olive oil as the sole contrast medium was studied in the remaining five horses. RESULTS: Injection with olive oil resulted in better distention and a complete filling of the nasolacrimal duct (ND) in all horses. Injection of 0.25 mmol/mL of gadolinium resulted in incomplete filling of the ND, whereas injection of 0.5 mmol/mL of gadolinium resulted in slightly better filling of the duct. The nondependent duct showed better distention compared to the dependent duct when scanning in lateral recumbency. No differences were observed between ducts in a dorsal recumbency. The degree of distention in dorsal recumbency was slightly less than the degree of distention observed in the nondependent ND in lateral recumbency. CONCLUSIONS: Magnetic resonance dacryocystography is a suitable technique for evaluating the nasolacrimal duct and can be performed during a normal magnetic resonance examination.

Background Endonasal access to the inferomedial and inferolateral intraconal space via the orbital floor has not been reported. The primary purpose of this study was to assess the feasibility of accessing the inferior intraconal space through the orbital floor via a transnasal prelacrimal approach. Secondarily, it aims to highlight anatomical relationships of neurovascular structures in this space, as a requirement to prevent complications. Methods Six cadaveric heads (12 sides) were dissected using a transnasal prelacrimal approach. The orbital floor, medial to the infraorbital canal, was removed and the periorbita opened to expose the inferior rectus muscle. The inferomedial and inferolateral intraconal space was accessed alongside the medial and lateral border of inferior rectus muscle, respectively. Various anatomical relationships of adjacent neurovascular structures were recorded, and the distances among the recti muscles and optic nerve were also measured. Results The infraorbital nerve is located at the inferolateral aspect of inferior rectus muscle. In the inferomedial intraconal space, we identified the inferomedial muscular trunk of the ophthalmic artery, optic nerve, and branches of the oculomotor nerve; whereas the inferolateral intraconal space contained the inferolateral muscular trunk of ophthalmic artery, branches of the oculomotor and nasociliary nerve, and abducens nerve. Distances from the medial, inferior, and lateral recti muscles to the optic nerve were (mean ± standard deviation) 4.70 ± 1.18 mm, 5.60 ± 0.93 mm, and 7.98 ± 1.99 mm, respectively. Distances from the inferior rectus muscle to the inferior borders of medial and lateral recti muscles were 4.45 ± 1.23 mm and 8.77 ± 1.80 mm. Conclusion It is feasible to access the inferior intraconal space through the orbital floor via a transnasal prelacrimal approach. The access may be subdivided into inferomedial and inferolateral corridors according to the entry point at the medial or lateral border of the inferior rectus muscle. Neurovascular structures in the inferior intraconal space are visualized directly, which should enhance their preservation.

Introduction Corroborating data suggest that the analysis of tear fluid might represent an additional tool in the ophthalmological practice. Areas covered The purpose of this review was to sum up the tear protein profiles in healthy and diseased ocular surface and to highlight biomarker usefulness in the early diagnosis as well as at follow-up. This analysis encompasses a deep examination of the protein profile expression under physiological and pathological conditions. Tear protein profile analysis will allow in the near future discriminating between different grades of inflammation, from acute trauma toward immune-, endocrine-, and nervous-related disorders of the ocular surface. Concluding remarks The review provides an overview of old and recent findings about inflammatory mediators identified at the ocular surface, under physiological and pathological conditions. To date, the analysis of tear fluid represents a new additional approach for diagnosis and management of ocular surface diseases. Understanding the pathophysiological mechanism could also offer significant advantages to develop strategies addressed to better clarify some complex ocular surface disorders. To sum up, the possibility to provide selective biomarkers as a future target of specific diseases should be considered for supporting diagnosis and management of ocular surface diseases.

Purpose Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features. Methods A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance. Results Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator. Conclusion Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.

Objective Dry eye syndrome in which tear fluid quality or abnormality, or kinetic abnormality is caused by various reasons, resulting in decreased tear film stability. In recent years, more and more results from the studies indicate that miRNA alterations are involved in dry eye syndrome. And miRNA‐146a‐5p is a key regulator to regulate the inflammatory response. In this paper, we demonstrated whether miRNA‐146a‐5p could cure dry eye syndrome by regulating target genes based on network analysis. Methods In current study, we collected the blood of patients with dry eye disease served as a model group; the blood of healthy people was served as control group. The expression of miRNA‐146a‐5p in the patients was detected by RT‐PCR, the genes controlled by miRNA‐146a‐5p were predicted by TargetScan, miRDB, miRWalk, and PicTar databases, and the genes regulated by miRNA‐146a‐5p which relative with dry eye disease were selected by drawing Venn diagram. Results The comparison of the general information between patients and healthy people was no significant difference, and it indicated that the two groups were comparable. The results of databases showed that IRAK1 was one of the target genes regulated by miRNA‐146a‐5p, and it is related to dry eye disease. The expression of miRNA‐146a‐5p was negatively related to IRAK1 mRNA and protein, while IRAK1 had a positive correlation with IL‐6, TNF‐α, and CBP proteins. Conclusion These results emphasized that miRNA‐146a‐5p could inhibit the expression of IRAK1, IL‐6, TNF‐α, and CBP to help reduce the inflammatory response in dry eye syndrome., IRAK1 is the target gene regulated by miRNA146a‐5p in dry eye syndrome.

OBJECTIVES/HYPOTHESIS Revision endoscopic dacryocystorhinostomy (END-DCR) is the preferred approach for failed primary surgeries, yet quality data on long-term outcomes are lacking. This study aimed to evaluate three aspects of revision END-DCR: 5-year success rates, patient satisfaction, and the primary surgical approach's possible impact on revision. METHODS This retrospective study included all revision END-DCRs conducted at Kaplan Medical Center between the years 2002 and 2015. For long-term follow-up analysis, two subgroups of first and second revision END-DCRs with a minimum of documented 5-year follow-up after surgery were defined. Data were analyzed according to the primary surgical approach. Surgical success was defined by either anatomical (observed patent lacrimal flow) or functional (symptoms cessation) success. Patient satisfaction was measured by a questionnaire. RESULTS After exclusions, a total of 45 eyes from 38 patients who underwent revision END-DCR surgeries were included in the study. The yearly success rates from immediate to 5 years following the first revision were 93.3%, 75.5%, 71.1%, 68.9%, 68.9%, and 68.9% for the entire cohort, respectively. Immediate and 5-year success rates following the second revision were 88.8% and 77.8%, respectively. Primary END-DCR showed favorable 5-year success rates and patient satisfaction over primary external dacryocystorhinostomy (EXT-DCR) in both first and second revisions, but this did not reach significance. CONCLUSIONS Revision END-DCR carries an excellent short-term success rate, which decreases mainly throughout the first 2 years following surgery. Postoperative follow-up should be maintained within this timeframe. Revision END-DCR following either primary endoscopic or EXT-DCR produces comparable surgical outcomes and patient-reported satisfaction. LEVEL OF EVIDENCE 3b Laryngoscope, 131:E682-E688, 2021.

Developmental remnants may follow segmental canalization of ectodermal epithelial cords forming the nasolacrimal drainage apparatus (NDA). This can result in false luminal "valves" along the path of the NDA, many of which have been named, but most have not been anatomically identified with consistency. By 1908, eight such "valves" were documented, those of: Foltz, Bochdalek, Rosenmuller, Huschke, Aubaret, Beraud or Krause, Taillefer, and Hasner or Cruveilhier or Bianchi. Digital subtraction dacryocystography (DS-DCG) is the highest spatial resolution imaging technique available to outline in vivo NDA anatomy, luminal profile, and pathology. We believe this is the first report of the conspicuousness and frequency of these "valves" on DS-DCG. We retrospectively analyzed routine DS-DCGs with normal findings for the presence and frequency of the eight NDA "valves." We examined 92 normal DS-DCGs on patients aged 14-82 years (71% female, 29% male). We observed "valves" most reliably in the inferior nasolacrimal duct: the inferior valve of Hasner (plica lacrimalis) was present in 98.9% of cases, and more superiorly, the valve of Taillefer (93.5%) and the valve of Krause (79.3%). Contrastingly, we infrequently identified the very superior "valves": Foltz or Bochdalek in 17.1%, Rosenmuller or Huschke in 46.4%, and Auberat in 40% of cases. Therefore, unlike the inferior NDA valves, these more superior "valves" were less consistently identified and are presumed to be simple mural mucosal irregularities rather than true structural valves. These findings will be useful in diagnostic interpretation of DS-DCGs and therapeutic planning for patients undergoing luminal procedures on the NDA. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.

Several ion channels and transporters regulate fluid secretion in salivary and lacrimal glands. In salivary glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increasing intracellular calcium concentrations. The chloride currents evoked by a TRPV4-specific activator (GSK1016790A) were identified as ANO1-mediated currents. Moreover, TRPV4 activation by an inositol 1,4,5-trisphosphate (IP3)-dependent mechanism was found to contribute to the muscarinic pathway of fluid secretion. Muscarinic stimulation of saliva and tear secretion was down-regulated in both TRPV4-deficient mice and in acinar cells treated with a TRPV4-specific antagonist (HC-067047). Furthermore, the temperature dependence of muscarinic salivation was shown to depend mainly on TRPV4. Our results suggest that TRPV4 interacts with IP3 receptors and ANO1 to regulate the muscarinic pathway that mediates salivation and lacrimation.-Derouiche, S., Takayama, Y., Murakami, M., Tominaga, M. TRPV4 heats up ANO1-dependent exocrine gland fluid secretion.

Chronic dry eye (keratitis sicca) is a significant problem that in certain populations can result in corneal desiccation and the potential for blindness. Therefore, novel treatments for such disorders might decrease patient morbidity. The present study aimed to investigate a potential treatment for chronic dry eye via a cadaveric feasibility study. On 10 cadaveric sides, the parotid gland branch of the auriculotemporal nerve (ATN) was identified and anastomosed to an anterior superficial temporal branch (STb) of this same nerve. The STb was then transposed anteriorly and sutured to the lacrimal gland. The parotid branch of the ATN was easily identified on all sides. The STb of the ATN was easily identified and mobilized on all sides. This latter nerve had adequate length to be moved to the ipsilateral lacrimal gland on all sides. Rerouting parotid gland secretomotor fibers to the superficial branch of the ATN and then moving this branch to the lacrimal gland is a feasible surgical maneuver based on our cadaveric study. Clinical studies are now necessary to show utility of this procedure in patients with chronic dry eye. Clin. Anat. 30:839-843, 2017. © 2017Wiley Periodicals, Inc.

Objective The purpose of this study was to establish the normal values of strip meniscometry (SM) as a lacrimal function test and to compare the results with Schirmer tear test I (STT I) in dogs, cats, and rabbits. Animals studied Sixty healthy adult dogs from twelve different breeds (120 eyes), twenty adult healthy domestic shorthair cats (40 eyes) and eighteen adult healthy New Zealand white rabbits (36 eyes) were used in this study. Procedures Lacrimal function was tested by SM tube in all animals. After 24 h at the same time of day, tear production was measured using STT I. Results Mean SM and STT I values for all of the dogs, cats, and rabbits were 9.66 ± 2.15 mm/5 s and 15.10 ± 3.06 mm/min; 10.50 ± 0.7 mm/5 s and 11.00 ± 1.41 mm/min; 4.72 ± 1.20 mm/5 s and 4.22 ± 2.47 mm/min, respectively. There was a correlation (r = 0.281; P = 0.018) between SM and STT I values in dogs, but no correlation was observed in cats and rabbits (P = 0.61, P = 0.06). No correlation was found between age of animals and obtained SM values in each species (P > 0.29). Sex had no effect on SM values in each species (P > 0.08). Conclusions The result of this study provided the normal clinical values of strip meniscometry as lacrimal function test in three species.

Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity. Within the lacrimal and salivary glands of NOD mice, CD8 T cells were proliferating, expressed an activated phenotype, and produced inflammatory cytokines. Transfer of purified CD8 T cells isolated from the cervical lymph nodes (LNs) of NOD mice into NOD-severe combined immunodeficiency recipients resulted in inflammation of the lacrimal glands, but was not sufficient to cause inflammation of the salivary glands. Lacrimal gland-infiltrating CD8 T cells displayed a cytotoxic phenotype, and epithelial cell damage in the lacrimal glands was observed in recipients of CD8 T cells regardless of the presence of CD4 T cells. Collectively, our results demonstrate that CD8 T cells have a pathogenic role in lacrimal gland autoimmunity. The gland-specific pathogenicity of CD8 T cells makes them a valuable resource to further understand the mechanisms that discriminate lacrimal versus salivary gland autoimmunity and for the development of new therapeutics that target the early stages of disease.

Purpose Ductal carcinomas (DCs) of the lacrimal gland are very rare but aggressive malignancies. We investigated DC of the lacrimal gland for potentially clinically actionable targets in the search for new therapeutic options. Methods Case 1: A 77-year-old man, presented with diplopia and xerophtalmia; case 2: A 53-year-old man, presented with headache, proptosis and chemosis and case 3: A 73-year-old man, presenting with chemosis and a corneal abscess. All three cases were characterized morphologically including immunohistochemistry and genetically with fluorescence in situ hybridization (FISH) and one case with next-generation sequencing (NGS) of cancer relevant genes. Results Cases 1 and 3 were composed of large, rounded, irregular cystic nodules of carcinoma cells with prominent central comedonecrosis, whereas case 2 had a scirrhous morphology. High expression of CK7, CK19, EMA, p53 and HER2 was characteristic for all three tumours. Androgen receptor was intensely positive in case 1, in scattered cells in case 2 and negative in case 3, whereas oestrogen and progesterone receptor were consistently negative. Genetically, a hemizygous deletion and a point mutation in PTEN were identified in case 1, whereas HER2 amplification was found in cases 2 and 3. Conclusion This study identified a spectrum of genetic events and pattern of protein expression in DC of the lacrimal gland similar to a subset of carcinomas of the breast and ductal carcinomas of the salivary glands. For therapeutic purposes, aberrations in several components of especially the HER2 signalling pathway could alleviate the effect of HER2-directed therapy illustrating an inadequacy of isolated HER2 testing.

We report a case of immunoglobulin G4-related disease (IgG4-RD) which presented with prurigo on the trunk and extremities. A 66-year-old man had a 2-month history of itchy erythematous papules on his trunk and extremities. Bilateral eyelid swelling and enlargement of the submandibular and parotid glands were also observed. Computed tomography revealed pleural thickening and diffuse pancreatic enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen obtained from an erythematous papule showed a perivascular inflammatory infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland biopsy revealed an infiltrate of abundant IgG4-positive plasma cells. Treatment with prednisolone resulted in improvement of the skin and other lesions along with a decrease in IgG4 serum levels. A flow cytometric assay revealed that percentages of interleukin (IL)-4- and IL-13-producing CD4(+) T cells were markedly higher in the circulation of the IgG4-RD patient than in that of healthy subjects. Moreover, those populations dramatically decreased after treatment. Thus, prurigo may be a skin manifestation of IgG4-RD and T-helper 2 cells may contribute to the pathogenesis.

Background We analyzed local control and early ocular toxicity after eye-sparing management of lacrimal gland carcinoma. Methods For consecutive patients with lacrimal gland carcinoma treated during 2007 to 2014, we reviewed tumor characteristics, treatment details, ocular toxic effects, and recurrence. Results Twenty patients, median age 55 years, were treated for lacrimal gland carcinoma during the study period; 11 had globe-sparing surgery. Seven patients had adenoid cystic carcinoma, 2 had carcinoma ex pleomorphic adenoma, and 1 each had high-grade and low-grade adenocarcinoma. Ten patients underwent postoperative radiotherapy, median 60 Gy (range, 52–64 Gy), 6 with concurrent chemotherapy. At a median of 30 months after radiation, all patients had dry eye syndrome, and 1 patient had severe corneal and conjunctival damage leading to enucleation. All 11 patients were disease free at last contact, median follow-up after surgery of 33 months. Conclusion An eye-sparing approach with surgery followed by adjuvant radiotherapy or chemoradiotherapy is feasible for selected patients with lacrimal gland carcinoma and is associated with a reasonable locoregional control and ocular toxicity profile. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Purpose Abnormalities of lacrimal punctum size and morphology probably contribute to excess tearing, with significant effects on quality-of-life for affected individuals. Our current understanding of normal punctal morphology originates from ex vivo studies, which are unlikely to capture the true nature of the living punctum. This study used enhanced depth anterior segment optical coherence tomography (OCT) to give improved characterization and understanding of lacrimal punctal structure. Methods Qualitative and quantitative assessments were performed on spectral domain OCT images collected prospectively from 40 lower puncta of 20 healthy volunteers. Results The average external lower lid punctal diameter was 0.646 mm (SD 150 μm) on OCT imaging, measured at the largest diameter, which was in parallel to the mucocutaneous junction. Fifty-five per cent of puncta appeared closed, whilst the eyelids were open. Fluid menisci were visible within 73% of puncta. A postpunctal ‘ampulla’ was visible within three systems, one of which was imaged through the conjunctival surface. Ampullary dilatation occurred laterally, rather than at the medial wall. Conclusion Optical coherence tomography provides quick and non-invasive assessment of the lacrimal punctum and its neighbouring tissue layers. This assessment of punctal size and morphology has the potential for further investigation of punctal physiology, for aiding diagnosis, and for monitoring the results of treatment. The average external diameter of the punctal opening measured in this study is greater than that recorded in anatomical textbooks.

Background Lacrimal gland carcinomas are rare. Identification of molecular abnormalities underlying lacrimal gland carcinogenesis is critical to the development of new targeted therapies for lacrimal gland carcinomas. The purpose of our study was to look for mutations that can be targeted as new treatments for lacrimal gland carcinomas. Methods Genomic DNA from patients with lacrimal gland epithelial neoplasms was analyzed. The Sequenom matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass ARRAY platform was used to profile 168 common oncogenic point mutations in 40 genes. Mutation frequency was assessed overall and by histologic diagnosis. These genetic mutations were then correlated with clinical outcomes in the patients. Results The study included 14 men and 10 women with a median age of 45 years (range, 17–75 years). The histologic diagnoses were as follows: adenoid cystic carcinoma (n = 16), low-grade carcinoma ex pleomorphic adenoma (n = 2), high-grade carcinoma ex pleomorphic adenoma (n = 2), squamous carcinoma (n = 1), and pleomorphic adenoma (n = 3). Analysis revealed 18 oncogenic mutations in 13 patients: KRAS mutations in 10 patients (46%), NRAS mutations in 2 patients (8%), MET mutations in 3 patients (13%), PIK3CA mutation in 1 patient (4%), and BRAF mutation in no patients. About half of the patients with adenoid cystic carcinoma had oncogenic mutations (7 of 16; 44%). Of the 16 patients with adenoid cystic carcinoma, 5 had KRAS mutations, 1 had MET mutations, and 1 had an NRAS mutation. Conclusion KRAS, NRAS, and MET mutations are frequent in epithelial neoplasms of the lacrimal gland, with the highest rate of mutations found in adenoid cystic carcinoma. Therapies targeting these genes may be effective treatments for lacrimal gland carcinomas. © 2015 Wiley Periodicals, Head Neck, 2015

Objective The lacrimal gland (LG) and the third eyelid gland (TELG) are two intraorbital glands that, in dogs, secrete the aqueous component of the tear film. Despite the central importance of these structures for maintaining ocular surface health, the gross anatomy of the glands remains understudied. We investigated the macroscopic morphometric characteristics of the LG and TELG in three different dog breeds. Procedures Twenty-six dog heads were dissected to expose the LG and TELG; the length, width, thickness, and weight of each were measured. During the dissections, the relationships between the glands and adjacent ocular structures and the blood and nerve supplies to the LG were photo-documented. Results The LG had a flat and irregular shape with morphological variations among dogs. The LG was located on the dorsolateral aspect of the globe underneath the orbital ligament. The average length, width, and thickness (SEM) of the LG (mm) were 16.5 ± 0.7, 12.5 ± 0.4, and 2.7 ± 0.1 and of the TELG 10.5 ± 0.6, 11.0 ± 0.3, and 3.3 ± 0.1, respectively. The mean weights (SD) of the LG and TELG (mg) were 315.7 ± 21.1 and 263.3 ± 13.2, respectively. Beagles were observed to have significantly smaller LGs compared to pit bull terriers and pointer mixed-breed dogs. Conclusions The present study provides detailed normative anatomical and morphometric data for the LG and TELG. These data will aid researchers investigating alterations induced by disease states and should inform strategies for the local delivery of pharmacologic and cellular therapeutics.

The aim of this retrospective study was to evaluate the results obtained in 353 dogs (420 eyes) using two different surgical techniques for correction of a prolapsed gland of the third eyelid: the Morgan's pocket technique and a technique combining Morgan's approach with a slightly modified periosteal anchoring technique of Stanley and Kaswan. The pocket technique was used in 234 eyes and the combined technique in 186 eyes. Successful repositioning was obtained in 95% of all cases, with recurrence occurring in 5%. The recurrence rate in large breed dogs such as the English Bulldog and Boxer was lower with the combined technique than with the pocket technique.

PURPOSE To describe a nasolacrimal duct (NLD) obstruction secondary to an ectopic tooth in a 5-year-old male Border collie. The dog was presented with a 1-month history of mucopurulent discharge from the left eye (OS) preceded by a lifelong history of epiphora OS. Treatment with neomycin/polymyxin B/dexamethasone ophthalmic solution had not improved the clinical signs, and the NLD was not patent when irrigated by the referring veterinarian. METHODS A complete ophthalmologic examination was performed followed by dacryocystorhinography and computed tomography (CT). RESULTS The ophthalmologic examination revealed marked mucopurulent discharge, mild conjunctivitis, slightly elevated STT measurements, and a negative Jones test OS. Both nasolacrimal puncta OS could be cannulated without resistance for approximately 1.5 cm. Upon irrigation, copious amounts of mucopurulent discharge were exited through the corresponding punctum, while no fluid could be detected at the nares. Dacryocystorhinography was performed. Radiographs revealed an ectopic left canine tooth within the left nasal cavity. A cystic dilation of the NLD was observed proximal to the ectopic tooth. Computed tomography was performed to determine the exact position of the tooth and possible involvement of adjacent structures; CT confirmed the previous imaging findings. Treatment with systemic antibiotics, NSAIDs, and ofloxacin ophthalmic solution led to resolution of the clinical signs within several days. Surgery was declined by the owner. CONCLUSION This is the first case report describing a blocked NLD due to an ectopic tooth in a dog. Ectopic teeth should be included as a differential diagnosis in cases of dacryocystitis and chronic epiphora in dogs.

Background To review the distribution of pathology in lacrimal gland biopsies performed in an Australian cohort. Design Retrospective review. Participants Two hundred sixty-eight lacrimal gland biopsies from 263 patients. Methods Pathology archives in South Australia and Victoria were searched for lacrimal gland biopsies performed between 1 January 1997 and 31 December 2012. Data retrieved included the year of biopsy, the histopathological diagnosis, patient age and gender. Main Outcome Measures Distribution of pathology affecting the lacrimal gland; patient age and gender. Results The distribution of lacrimal gland pathology was: inflammations and vasculitides 50.0%, lymphomas 19.8%, lymphoid hyperplasias 12.3%, benign epithelial tumours 7.8% (all pleomorphic adenomas), malignant epithelial tumours 4.1%, dacryops 3.0% and miscellaneous 3.0%. The mean age was 52 years, with lymphoma affecting the oldest patient group (64.6 years) and sarcoidosis the youngest (40.6 years). Of the patients with biopsy-confirmed dacryoadenitis, biopsy revealed a specific diagnosis in 34% of cases. Immunoglobulin G4-related disease was the most common ‘specific’ dacryoadenitis. Significantly more pleomorphic adenomas were diagnosed in the period 1997–2004 than the period 2005–2012 inclusive, but there were no other significant changes in the distribution of pathology over time. Conclusions Two thirds of dacryoadenitis was ‘non-specific’, two thirds of epithelial tumours were pleomorphic adenomas and approximately two thirds of all lacrimal gland biopsies were accounted for by inflammations and lymphoid hyperplasias. The ratio of inflammations to neoplasias will be significantly influenced by the clinician's threshold for biopsying patients presenting with features of dacryoadenitis.

Purpose To investigate the changes in the tear flow velocities caused by ageing. Methods Ninety-nine subjects (41 men, mean age 48.3 ± 20.7 years) were recruited from the Department of Ophthalmology of the Ehime University Hospital. None of the subjects had serious abnormalities of the external surface of the eye. The Krehbiel flow of tears was determined by 40-μm polymethylmethacrylate (PMMA) beads suspended in a fluorescein sodium solution (PPF). The movement of the beads was video recorded through a slit-lamp during normal blinking. The flow of the beads was determined with a Motion analyzer®software (KEYENCE Co., Osaka, Japan). The velocity of the beads in young age, 20–40 years, middle age, 41–60 years and old age, ≥61 years, groups was determined. Results The equation describing the velocity (mm/second) of the PMMA particles as a function of age in the lower tear meniscus measured in the direction of the lacrimal punctum was Y = 2.49−0.04X, where Y = velocity and X = age (r2 = 0.214; p

Objective To evaluate endodontic paper point tear test (PPTT) in rabbits and compare changes in corneal touch threshold (CTT) induced by Schirmer tear test (STT) and PPTT. Normal corneal sensitivity recovery time after both tear tests was also measured. Also, mean PPTT and STT values were obtained. Methods Tear production of 20 eyes, from 10 rabbits, was evaluated using STT and the PPTT. Central corneal touch threshold was measured by a Cochet-Bonnet esthesiometer before any tear test was performed (zero time), immediately after the test (1 min), and consecutively at 6, 11, 16, and 26 min. Tests were conducted on three consecutive days: Day 1 – control condition, no tear tests performed only the CTT; Day 2 – CTT before and after PPTT; and Day 3 – CTT before and after STT. CTT values were compared using repeated measures ANOVA. Results Corneal touch threshold was significantly increased for at least 16 min after STT, indicating STT causes corneal discomfort. No difference was found between CTT following PPTT and controls, indicating PPTT caused minimal corneal discomfort. The mean (±SD) value for STT was 5.2 ± 1.0 mm/min and for PPTT was 13.8 ± 1.5 mm/min. Discussion The aqueous fraction of rabbit's tears can be successfully measured by PPTT. This report established reference values for PPTT in rabbits. Additionally, the absence of a significant difference in CTT after PPTT compared with controls shows that PPTT is well tolerated by rabbits. Considering the improved comfort (compared with STT), accuracy, and low cost, PPTT is a bona fide method of measuring aqueous tear production in rabbits.

Objectives To determine the prevalence of selected coagulase-positive methicillin-resistant Staphylococcus aureus (MRS) in the conjunctival sac in a group of healthy dogs and to compare the prevalence of ocular MRS colonization with colonization of typically assessed body sites including the nasal cavity and rectum. Animals studied 123 healthy dogs were used in the prevalence study: 40 dogs from a shelter and 83 privately owned dogs. Procedures The sampling procedure included culturing three separate sites per subject in the following order: the lower conjunctival fornices, the nares, and rectum. Results A low prevalence of 1.6% (2/123) of MRS was detected in healthy dogs. Methicillin-resistant Staphylococcus pseudintermedius was isolated from two dogs, one from a conjunctival swab and the other from a rectal swab. Conclusion The survey data indicate the ocular surface is a potential site of MRS colonization, although the prevalence was low in healthy dogs.

Objective Primary Sjogren's syndrome (SS) is characterized by autoimmune activation and loss of function in secretory epithelia. The present study was undertaken to investigate and characterize changes in the epithelia associated with the loss of gland function in primary SS. Methods To identify changes in epithelial gene expression, custom microarrays were probed with complementary RNA (cRNA) isolated from minor salivary glands (MSGs) of female patients with primary SS who had low focus scores and low salivary flow rates, and the results were compared with those obtained using cRNA from the MSGs of sex-matched healthy volunteers. The effect of bone morphogenetic protein 6 (BMP-6) on salivary gland function was tested using adeno-associated virus–mediated gene transfer to the salivary glands of C57BL/6 mice. Results A significant increase in expression of BMP-6 was observed in RNA isolated from SS patients compared with healthy volunteers. Overexpression of BMP-6 locally in the salivary or lacrimal glands of mice resulted in the loss of fluid secretion as well as changes in the connective tissue of the salivary gland. Assessment of the fluid movement in either isolated acinar cells from mice overexpressing BMP-6 or a human salivary gland cell line cultured with BMP-6 revealed a loss in volume regulation in these cells. Lymphocytic infiltration in the submandibular gland of BMP-6 vector–treated mice was increased. No significant changes in the production of proinflammatory cytokines or autoantibodies associated with SS (anti-Ro/SSA and anti-La/SSB) were found after BMP-6 overexpression. Conclusion In addition to identifying BMP-6 expression in association with xerostomia and xerophthalmia in primary SS, the present results suggest that BMP-6–induced salivary and lacrimal gland dysfunction in primary SS is independent of the autoantibodies and immune activation associated with the disease.

Tumours of the lacrimal gland are rare, but the prognosis may be grave. To date, no population-based incidence and distribution data on lacrimal gland tumours exist. In addition, almost nothing is known about the genetic profile of epithelial tumours of the lacrimal gland. We collected specimens and clinical files on all biopsied lacrimal gland lesions in Denmark over a 34-year period and re-evaluated the diagnosis to provide updated population-based incidence rates and epidemiological characteristics. Clinical data regarding symptoms, clinical examinations, treatment and follow-up were collected for patients with adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (Ca-ex-PA) and mucoepidermoid carcinoma (MEC). Using RT-PCR, FISH, immunohistochemistry, Q-PCR and high-resolution array-based comparative genomic hybridization (arrayCGH) we explored the genetic characteristics including copy number alterations (CNA) in ACC, PA, Ca-ex-PA and MEC. The incidence of biopsied lacrimal gland lesions was 1.3/1,000,000/year, and ~50% were neoplastic lesions. Of these, 55% were malignant tumours with epithelial tumours as the most frequent. The overall incidence was increasing, and this was caused by an increase in biopsied non-neoplastic lesions. We found that 10/14 ACCs either expressed the MYB-NFIB fusion gene and/or had rearrangements of MYB. All ACCs expressed the MYB protein. ACC was characterized by recurrent copy number losses involving 6q, 12q and 17q and gains involving 19q, 8q and 11q. ArrayCGH revealed an apparently normal genomic profile in 11/19 PAs. The remaining 8 PAs had recurrent copy number losses involving 1p, 6q, 8q and 13q and gain involving 9p. PA expressed PLAG1 in all tumours whereas only 2/29 tumours expressed HMGA2. Ca-ex-PA was characterized by recurrent copy number gain involving 22q. PLAG1 was expressed in 3/5 Ca-ex-PA whereas none of these tumours expressed HMGA2. MEC expressed the CRTC1-MAML2, and this fusion was found to be tumour-specific for lacrimal gland MEC. In conclusion, lacrimal gland lesions that require pathological evaluation are rare in the Danish population, and the incidence rate of biopsied benign lesions is increasing. Epithelial tumours of the lacrimal gland are molecularly very similar to their salivary gland counterparts in the expression of the tumour-specific fusion genes and in their genomic imbalances as demonstrated by arrayCGH. MYB-NFIB is a useful biomarker for ACC and MYB, and its downstream target genes may be potential therapeutic targets for these tumours.

Purpose To describe a new method of measuring early phase tear clearance by anterior segment optical coherence tomography (AS-OCT). Methods Sixty normal subjects were divided into a young group (30 subjects; 29.6 ± 7.2 years) and an elder group (30 subjects; 71.4 ± 10.8 years). AS-OCT (CASIA SS-1000, Tomey, Japan) with customized software was used to record the tear meniscus at the centre of the lower eyelid. Five microlitres of lukewarm saline solution was dropped into the lower conjunctival sac, and an image of the tear meniscus was obtained immediately and again 30 seconds after natural blinking. The tear meniscus height (TMH) and tear meniscus area (TMA) were measured in the AS-OCT images, and the percentage decrease in the TMH and TMA was used as a measure of the tear clearance. Correlations between tear clearance and clinical features including degree of conjunctivochalasis, degree of protrusion of inferior lacrimal punctum, distance of lacrimal punctum from the Marx line and fluorescein clearance rates were also determined in another healthy population consisting of 30 subjects. Results The OCT tear clearance rate was 35.2 ± 11% for TMH and 28.1 ± 12.4% for TMA in the young group, and 12.4 ± 7.3% and 6.2 ± 9.1%, respectively in the elder group. The differences were significant for both the TMH (p = 0.017) and the TMA (p = 0.024). The OCT-determined tear clearance was positively correlated with the fluorescein clearance rate, and negatively correlated with the distance between the lacrimal punctum and Marx line, degree of conjunctivochalasis and degree of lacrimal punctum protrusion. Conclusion AS-OCT can be used as a rapid, non-invasive and quantitative method of determining the early phase tear clearance rate in a normal healthy population.

Diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) constitute two distinct subtypes of non-Hodgkin lymphoma (NHL) associated with considerable morbidity and mortality. Marked diversities with regard to molecular biology and clinical features are recognized in different subsets of the two lymphomas. Because these differences could be related to the location of the lymphoma, it is of interest to investigate the clinical and histopathological features of DLBCL and MCL involving the ocular adnexal region (i.e. the orbit, eyelids, conjunctiva, lacrimal gland and lacrimal sac). Similarly, the lacrimal gland is the only glandular structure within the orbit. Because the lacrimal gland represents an important part of the immunological system, it is of interest to investigate lymphomas involving this location with regard to clinical and histological characteristics. Purpose: To characterize the clinical and histopathological features of Danish patients with DLBCL of the ocular adnexal region between 1980 and 2009 and of Danish ocular adnexal MCL patients from 1980 to 2005. Furthermore, the aim of this PhD was to review all specimens from patients with lymphoma of the lacrimal gland in Denmark between 1975 and 2009 to determine the distribution of lymphoma subtypes of the lacrimal gland and to describe the clinicopathological features of these patients. Results: A total of 34 patients with DLBCL and 21 with MCL of the ocular adnexal region were identified. Twenty-seven patients had lacrimal gland lymphoma, including four DLBCLs and three MCLs from studies I and II. Elderly patients predominated in all three groups, with median ages of 78, 75 and 69 years in the DLBCL, the MCL and the lacrimal gland lymphoma groups, respectively. MCL patients had a preponderance of males, whereas females prevailed among lacrimal gland lymphoma patients. The orbit was the most common site of involvement in DLBCL and MCL. Most DLBCL patients had unilateral involvement, while MCL patients had a high frequency of bilateral involvement. Similarly, localized lymphoma was relatively frequently seen in DLBCL patients in contrast to the predominance of disseminated lymphoma in the MCL group. The majority of lacrimal gland lymphomas were low grade, and the distribution of subtypes was as follows: extranodal marginal zone lymphoma, 10 (37%); follicular lymphoma, 5 (19%); DLBCL, 4 (15%); MCL, 3 (11%); chronic lymphocytic leukaemia/small lymphatic lymphoma, 2 (7%); and unclassified B-cell lymphoma, 3 (11%). The overall survival rates at 3 and 5 years for the entire study group of DLBCL were 42% and 20%, whereas 58% and 22% of MCL patients were alive 3 and 5 years after the time of diagnosis. The 5-year overall survival rate of lacrimal gland lymphoma patients was 70%. Concordant bone marrow involvement and the International Prognostic Index score were predictive factors for the overall survival in the DLBCL group in Cox regression analysis. Rituximab-containing chemotherapy was associated with an improved survival rate in MCL patients. Conclusions: Diffuse large B-cell lymphoma and MCL involving the ocular adnexal region and lymphoma of the lacrimal gland are prevalent among elderly patients. The overall prognosis in DLBCL and MCL was poor, whereas the prognosis for lacrimal gland lymphoma patients was relatively good. Concordant bone marrow involvement and the International Prognostic Index score were independent predictive factors for mortality in the DLBCL group. Chemotherapy containing rituximab significantly improved survival in the MCL group.

Fine-needle aspiration cytology (FNAC) of orbital lesions is now increasingly popular. Because of its unique location and the occurrence of varieties of lesions, diagnosis of orbital lesion is a challenge to the cytopathologists. FNAC of orbital and eyelid tumors is a suitable diagnostic technique that necessitates close co-operation between the ophthalmologist and pathologist. No radical procedure should be planned on the basis of FNAC, but it allows the diagnosis of a new primary lesion or the recurrence or metastasis of a tumor and can be done to identify lesions that require either specific medical therapy, as in nonresectable, inflammatory, and lymphoid tumors, or limited surgery for benign resectable neoplasms. With the help of various ancillary techniques a definitive diagnosis is possible on orbital and adnexal lesions. It is essential to have a detailed knowledge on the FNAC of these lesions and their potential pitfalls. In this present review, we have discussed various orbital lesions, their clinical presentations, cytomorphology, and ancillary techniques to confirm the diagnosis.

Immunoglobulin G4-related disease (IgG4-RD) is a recently described entity with protean manifestations. We describe a novel case of IgG4-RD with hypergammaglobulinemic hyperviscosity responsive to fludarabine and rituximab. A 33-year-old Asian man developed bilateral lacrimal gland and submandibular salivary gland swelling with cervical lymphadenopathy. Biopsies of the affected tissues revealed reactive follicular hyperplasia. Seven years later, he presented with bilateral retinal hemorrhages due to hyperviscosity syndrome from profound polyclonal increase in IgG, including marked IgG4 elevation. Despite plasmapheresis, overproduction of IgG continued and he was refractory to systemic steroids, azathioprine, interferon alpha, and cyclophosphamide. IgG4-RD was suspected following a myocardial infarction and detection of aneurysmal coronary arteries indicating large vessel vasculitis. Review of the cervical lymph node and lacrimal gland biopsies with immunohistochemical staining for IgG4-positive plasma cells confirmed IgG4-RD. B-cell depletion with rituximab produced a partial response, but clinical symptoms and elevated protein levels persisted. Fludarabine was added to rituximab to suppress T-cell activity, and this resulted in an excellent clinical and biochemical response. Combination therapy with fludarabine and rituximab in IgG4-RD has not previously been reported and can be considered in patients with severe refractory disease.

Objective To investigate the density and distribution of conjunctival goblet cells (GC) and study the anatomy and microscopic characteristics of glands associated with the eye in chinchillas (Chinchilla Laniger). Procedure 12 chinchillas were included in the study. Conjunctiva (divided into four regions), eyelids, and glands were embedded in paraffin wax, sectioned, stained, and analyzed. Results Highest GC densities were found in the palpebral region of the nasal and temporal conjunctiva of both eyelids (GC index: 25.1–18.2%), and lowest densities, in the bulbar and marginal region of the nasal and temporal conjunctiva of both eyelids (GC index: 1.5–0.0%). Meibomian glands extend along the entire length of both eyelids, and the whole glandular complex broadens toward the temporal canthus. This is macroscopically visible through the conjunctiva. The openings of the Meibomian glands are macroscopically not discernible. The light pink, smooth, and crescent-shaped lacrimal gland lies next to the aforementioned broadened part of the Meibomian glands in the temporal canthus. The whitish, 0.9-cm-long, smooth Harderian gland is firmly attached to the posterior part of the globe and extends nasally from the optic nerve to the equator. Furthermore, chinchillas possess two lacrimal puncta, situated on the inner conjunctival surface of both eyelids near the medial canthus. A pigmented lacrimal canaliculus originates from each punctum. The vestigial nictitating membrane is supported by a hyaline cartilage and is pigmented at its free margin. Conclusions Chinchillas possess a Harderian gland, a lacrimal gland, and Meibomian glands. The GC density in the nasal and temporal palpebral conjunctiva is higher than in guinea pigs.

We have read the article by Green et al.1 with great interest, given the results from their review, the recommendation of performing a mucosal sparing technique when performing dacryocystorhinostomy seems logical. However, based on our experience we would like to make some comments on this subject. This article is protected by copyright. All rights reserved.

Objective: The aim of the current study was to determine the proportion of trigeminal primary afferent neurons that innervate the intracranial vasculature, and other craniofacial tissues, that are also 5 hydroxy triptamine (5-HT)1D receptor immunoreactive. Methods: Retrograde tracing and immunohistochemistry was used to identify 5-HT1D receptor labeled trigeminal primary afferent neurons that innervate the lacrimal gland (n = 3 animals), nasal mucosa (n = 3 animals), and the intracranial vasculature (middle meningeal artery in the dura [n = 3 animals] and middle cerebral artery [n = 3 animals]). Results: The percentage of neurons that were 5-HT1D receptor immunoreactive was greater for primary afferent neurons innervating the middle meningeal artery (41.8 ± 1%) than those innervating the middle cerebral artery (28.4 ± 0.8%), nasal mucosa (25.6 ± 1%), or lacrimal gland (23.5 ± 3%). For each retrograde labeled population, the 5-HT1D receptor immunoreactive cells were among the smallest of the retrograde labeled cells. Conclusions: These findings provide a basis for understanding the role of 5-HT1D receptor agonists (eg, triptans) in the treatment of primary vascular headaches and suggest that the selectivity of triptans in the treatment of these headaches does not appear to result from specific localization of the 5-HT1D receptor to trigeminovascular neurons alone.

BACKGROUND: Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye-sparing surgery) and clarify the role of adjuvant RT for this rare disease. METHODS: Forty-six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty-seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye-sparing surgery; 64% of the orbital exenteration group and 83% of the eye-sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow-up time for all patients was 38 months (range, 3-460 months). RESULTS: For the orbital exenteration and eye-sparing surgery groups, the 5-year overall survival (OS) rates were 59% and 62%, and the 5-year disease-free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1-2 vs T3-4) was associated with OS (P = .02), and tumor size ( 3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye-sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT. CONCLUSIONS: For appropriately selected patients, an eye-sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors. Cancer 2011. © 2011 American Cancer Society.

Cytosolic and secretory carbonic anhydrase isoenzymes (CA-II and CA-VI, respectively) were detected by immunohistolocalization using specific canine CA-II and CA-VI antisera. CA-II and CA-VI were identified in glands associated with the canine lacrimal apparatus, such as lacrimal gland, superficial gland of the third eyelid (third eyelid gland) and tarsal gland. CA-II and CA-VI mRNA signals were also detected by reverse-transcriptase polymerase chain reaction in the same tissues. Some serous acinar cells and duct segments in the lacrimal gland and serous acinar cells in the third eyelid gland were immunopositive for anti-CA-II and CA-VI antisera. In particular, some immunopositive acini to CA-II and CA-VI on the edge of the third eyelid gland are histologically similar to sebaceous gland cells. Sebaceous gland cells in the tarsal and ciliary glands also showed immunopositivity to both CA antisera. CA-II and CA-VI gene transcripts were detected in the same regions. These results suggest that secreted CA-VI may form together with cytosolic CA-II, a high-activity isozyme mostly considered as a bicarbonate producer, in a mutually complementary system for the maintenance of bicarbonate levels to regulate pH in tear fluid and protect the corneal epithelia against injuries. In sebaceous gland cells in the lacrimal apparatus, CA-VI may be related to lipogenesis in an unknown function.