Search

Background: The present study reviewed the clinicopathological features and outcomes of bilateral lacrimal gland lesions. Methods: The data of 113 patients who underwent lacrimal gland biopsy at the West China Hospital of Sichuan University, China, between January 1, 2010, and December 31, 2021, are presented in this case series. The patients all presented with bilateral lacrimal gland lesions. The collected data included patient demographics, clinical features, the results of laboratory examinations, imaging presentations, histopathological diagnoses, treatments, and outcomes. Results: The mean age of the 113 enrolled patients was 47.4 ± 14.9 years (range, 11–77 years) with a predominance of females (54.9%, n = 62). The lacrimal gland was the source of the majority of biopsy tissue (98.2%, n = 111). The most prevalent etiology was immunoglobulin G4-related ophthalmic disease (IgG4-ROD) (32.7%, n = 37), followed by idiopathic orbital inflammation (IOI) (28.3%, n = 32), mucosa-associated lymphoid tissue (MALT) lymphoma (17.7%, n = 20), reactive lymphoid hyperplasia (RLH) (10.6%, n = 12), and mantle cell lymphoma (4.4%, n = 5). Patients with IOI were significantly younger than those with IgG4-ROD and MALT lymphoma (t = 2.932, P = 0.005; t = 3.865, P<0.001, respectively). Systemic symptoms were more prevalent among patients with IgG4-ROD (χ2 = 7.916, P = 0.005). The majority of patients were treated with surgery (53.1%, n = 60), with surgery combined with corticosteroid therapy (21.2%, n = 24) being the second most common treatment. The majority of patients (91.2%, n = 103) attained complete resolution, stable disease, or significant improvement. Conclusion: In conclusion, there are several aetiologies associated with bilateral lacrimal gland lesions, the most prevalent being IgG4-ROD, IOI, and MALT lymphoma. Systemic symptoms were more common in patients with IgG4-ROD. The majority of patients who presented with bilateral lesions of the lacrimal glands responded satisfactorily to treatment, with favorable results. [ABSTRACT FROM AUTHOR]

Objectives: The red panda is currently the only surviving member of the Ailuridae family in the Caniformia suborder. In this study, we provide data on anatomical, morphometric, histological and histochemical examination of the orbital region, eyelids, orbital gland, and eye tunics in two adult males Ailurus fulgens fulgens from the Wroclaw Zoological Garden, Poland. Methods: The study involved morphometric analysis of the eyeball and selected accessory organs of the eye, along with analysis of the bony orbit, including its morphometry, macroscopic, and microscopic evaluation. Microscopic evaluation encompassed histological and histochemical staining, with the former involving hematoxylin & eosin (H&E), Movat pentachrome, picro-Mallory trichrome, Fontana-Masson, and the latter including PAS, AB pH 1.0, AB pH 2.5; AB pH 2.5/PAS, and HDI. Results: The upper (UE) and lower (LE) eyelids presented well-developed tarsal glands, sebaceous glands, and a characteristic simple alveolar gland (producing a mucous secretion). The palpebral part of the lacrimal gland was present. A single lymphoid follicle was observed only in the upper eyelids. The superficial gland of the third eyelid (SGTE) was a multilobar acinar complex that produces mucous secretion and is contained within the interlobular ducts of numerous aggregates of lymph nodes. The third eyelid (TE) was T-shaped and composed of hyaline tissue, containing CALT. The lacrimal gland (LG) also revealed a multilobar acinar complex that produced mucous secretion, with a single lymphoid follicle. The cornea consisted of 4 layers, as Bowman's membrane was absent. The Vogt palisades composed of 7–10 layers of epithelial cells were demonstrated. The pupil was horizontally ovoid at rest (post-mortem). The sphincter pupil and the dilator pupil were well developed. Macroscopically, the tapetum lucidum appeared as a milky, non-opalescent crescent. Histologically, the choroidal tapetum lucidum cellulosum consisted of 5 to 9 layers of loosely packed oval cells. The retina showed a composition similar to that of terrestrial nocturnal carnivores. Conclusions: The results of our research indicate that the anatomical features of the eye and orbital region in the red panda share similarities with those described in the Musteloidea clade, as well as the Canidae and Ursidae families. [ABSTRACT FROM AUTHOR]

Orbital inflammatory disease (OID) is a heterogeneous group of immunologic disorders whose etiology is often non-specific despite routine investigation. In this proof-of-concept study, metagenomic deep sequencing (MDS) is applied to examine host gene expression in two subtypes of OID. Prospectively collected lacrimal gland tissue from patients with OID was processed for MDS. Differential gene expression analysis was performed to evaluate for host transcriptome signatures. Proof-of-concept comparison was made between histologically confirmed samples of idiopathic dacryoadenitis and IgG4-related disease (IgG4-RD). Twelve genes were identified to be differentially expressed between idiopathic dacryoadenitis and IgG4-RD. Differences in innate humoral immunity gene expression were observed. Several additional genes of interests were also found to be upregulated in idiopathic dacryoadenitis. A unique transcriptome signature was found when comparing idiopathic dacryoadenitis to IgG4-RD. This suggests that MDS can identify differentially expressed genes in OID. Such insight could potentially provide a better understanding of host gene expression and the inflammatory pathways involved in OID. [ABSTRACT FROM AUTHOR]

To investigate the utility of a hand-held digital otoscope for nasal endoscopy and as a pedagogy tool for residents and fellows in patients undergoing external dacryocystorhinostomy (DCR) surgery A digital otoscope (MS450-NTE, Teslong Inc., USA) comprising a digital screen device and a connectible camera probe was used for performing nasal endoscopy. Inspection of nasal cavities was performed pre-, intra-, and post-operatively in sequential patients with nasolacrimal duct obstruction, who underwent DCR or lacrimal probing. Images (1920 × 1080 pixels) and videos (1280 × 720 pixels) were captured. The device was also used for training residents and fellows in performing nasal endoscopy, and to teach basic concepts. The digital otoscope could be used for routine outpatient nasal examination and for performing minor procedures. 53.8% (n = 13) of ophthalmology trainees had never observed nasal endoscopy and 84.6% could not identify more than one major structure correctly prior to the current training. Post-training, all trainees could independently perform nasal endoscopy with the device and 76.9% identified all structures correctly. A digital otoscope with a camera probe is a handy tool for nasal endoscopy and pedagogy. Low-cost gadgets such as this device can effectively be used for performing outpatient nasal endoscopy when expensive endoscopes are unavailable and in peripheral healthcare centers. [ABSTRACT FROM AUTHOR]

Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo assess the management of patients with congenital nasolacrimal duct obstruction (CNLDO) in a paediatric population and review the long-term outcomes over a 5-year interval, with particular emphasis on the difference between patients with trisomy 21 and those without trisomy 21.This single-centre, retrospective, cross-sectional, case review study included patients suffering from CNLDO at Alder Hey Children’s Hospital NHS foundation Trust. Patients were divided into two groups: Non-trisomy 21 and trisomy 21. Patients were followed-up for a 60-month interval. Patients aged <12 months at the time of surgery, patients with <60 months of follow-up data and patients with acquired nasolacrimal duct obstruction were excluded. The main outcome measures were discharge rates in patients undertaking primary intervention with syringe and probe (S&P), number of patients requiring further treatment with lacrimal intubation or dacryocystorhinostomy (DCR) and overall symptom-free periods post-treatment.Ninety-three patients (142 eyes) were included. The mean number of surgical interventions was 1.53 ± 0.65. The mean interval between the 1st and 2nd intervention was 15.54 ± 16.33 months. There was a trend towards greater success rates non-trisomy 21 patients versus patients with trisomy 21 (p = 0.1352). The average symptom-free period after the final intervention was 44.31 ± 20.68 months, significantly longer in the non-trisomy 21 group compared to the trisomy 21 group (p = 0.0074).The overall success rate after primary S&P was 55.9%. Our results suggest that in trisomy 21 patients suffering from CNLDO, a one-stage intervention with primary monocanalicular intubation should be considered instead of sequential approach. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). Methods: Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. Results: Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p < 0.05). The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were independently associated with active TAO (all p < 0.05). The combination of the EOM-SIRmean, LG-SIRmean, and LG-FFmean values showed better performance than the EOM-SIRmean value alone in staging TAO in both the training (AUC, 0.820 vs 0.793; p = 0.016) and validation (AUC, 0.751 vs 0.733, p = 0.341) cohorts. Conclusion: Dixon MRI-based parameters of EOMs, LGs, and IF are useful for differentiating active from inactive TAO. The integration of multiple parameters can further improve staging performance. Critical relevance statement: In this study, the authors explored the combined value of quantitative parameters of EOMs, IF, and LGs derived from Dixon MRI in staging TAO patients, which can support the establishment of a proper therapeutic plan. Key Points: The quantitative parameters of EOMs, LGs, and IF are useful for staging TAO. The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were found to independently correlate with active TAO. Joint evaluation of orbital tissue improved the ability to assess TAO activity. [ABSTRACT FROM AUTHOR]

Background and Purpose: to compare the results of probing alone versus primary silicone intubation in cases of complex congenital NLDO. Methods: The study was done in ophthalmology department, Zagazig university hospitals from May 2022 to December 2023. Patients with complex CNLDO in children aged 1 - 4 years were included. We excluded cases of simple CNLDO, failed previous probing or intubation. Patients were divided randomly into two groups. The first group (group I) (32) eyes were treated with intubation and the second group (group II) (32) eyes were treated with probing and syringing. Results: 64 patients with complex type of CNLDO were enrolled. There was no significant difference between both groups regarding age (P = 0.990) and gender (P = 0.448). Failure rates were significantly higher in group II than in group I at one week (40.6 percent vs. 15.6 percent, P = 0.026). The results remained constant at the first and third month postoperative in which the failure rates at group II vs group I were (56.3 % vs. 15.6 %, P 0.001), and the results were also the same at the fourth and sixth month with the failure rates at group II vs group I were (68.8 % vs 15.6 %, P 0.001). Conclusion: Primary silicone intubation is recommended in cases of complex CNLDO because it produces better results than probing and has a longer success rate. [ABSTRACT FROM AUTHOR]

Simple Summary: Adenylyl cyclase is an enzyme that plays an important role in cellular signalling in mammals. This review gathers current understanding of the role of adenylyl cyclase in the eye, covering the cornea, lens, retina, lacrimal gland and tear film, and explores their potential as targets for therapeutic innovation. Adenylyl cyclases (ACs) are a group of enzymes that convert adenosine-5′-triphosphate (ATP) to cyclic adenosine 3′,5′ monophosphate (cAMP), a vital and ubiquitous signalling molecule in cellular responses to hormones and neurotransmitters. There are nine transmembrane (tmAC) forms, which have been widely studied; however, the tenth, soluble AC (sAC) is less extensively characterised. The eye is one of the most metabolically active sites in the body, where sAC has been found in abundance, making it a target for novel therapeutics and biomarking. In the cornea, AC plays a role in endothelial cell function, which is vital in maintaining stromal dehydration, and therefore, clarity. In the retina, AC has been implicated in axon cell growth and survival. As these cells are irreversibly damaged in glaucoma and injury, this molecule may provide focus for future therapies. Another potential area for glaucoma management is the source of aqueous humour production, the ciliary body, where AC has also been identified. Furthering the understanding of lacrimal gland function is vital in managing dry eye disease, a common and debilitating condition. sAC has been linked to tear production and could serve as a therapeutic target. Overall, ACs are an exciting area of study in ocular health, offering multiple avenues for future medical therapies and diagnostics. This review paper explores the diverse roles of ACs in the eye and their potential as targets for innovative treatments. [ABSTRACT FROM AUTHOR]

Sjögren's disease (SjD) is a chronic, progressive autoimmune condition of exocrine and extraglandular tissues. It can present with isolated disease characterized by lymphocytic infiltration of salivary or lacrimal glands, but in approximately one-third of the patients, lymphocytic infiltration extends beyond exocrine glands to involve extraglandular organs such as the lungs. Pulmonary complications have been reported to occur between 9 and 27% of patients with SjD across studies. Respiratory manifestations occur on a spectrum of severity and include airways disease, interstitial lung disease, cystic lung disease, and lymphoma. Lung involvement can greatly affect patients' quality of life, has a major impact on the overall prognosis, and frequently leads to alteration in the treatment plans, highlighting the importance of maintaining a high index of clinical suspicion and taking appropriate steps to facilitate early recognition and intervention. [ABSTRACT FROM AUTHOR]

Basement membrane (BM) component deposition is closely linked to the establishment of cell polarity. Previously, we showed that Prickle1 is crucial for BM deposition and cell polarity events in tear duct elongation. To gain a deeper understanding of the intimate relationship between BM formation and cell polarity, we generated induced pluripotent stem cells (iPSCs)‐derived embryoid bodies (EBs) with a basement membrane separating the visceral endoderm (VE) and inner EB cell mass. We found that Prickle1 was highly expressed in VE of the normal EBs, and the Prickle1 mutant EBs displayed severely impaired BM. Notably, the formation of the basement membrane appeared to rely on the proper microtubule network of the VE cells, which was disrupted in the Prickle1 mutant EBs. Moreover, disruption of vesicle trafficking in the VE hindered BM secretion. Furthermore, reintroducing Prickle1 in the mutant EBs completely rescued BM formation but not the apicobasal cell polarity of the VE. Our data, in conjunction with studies by others, highlight the conserved role of Prickle1 in directing the secretion of BM components of the VE cells during embryonic germ layer differentiation, even in the absence of established general polarity machinery. Our study introduces a novel system based on iPSCs‐derived EBs for investigating cellular and molecular events associated with cell polarity. [ABSTRACT FROM AUTHOR]

The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells. Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination. Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED. The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence and risk factors for inflammatory conditions among patients with primary acquired nasolacrimal duct obstruction (PANDO). Methods: A retrospective case-control study was conducted among patients of Clalit Health Services (CHS) in Israel from 2001 to 2022. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Differences in demographic characteristics, ocular surface, eyelid, upper airway, and systemic diseases were assessed between the groups, and odds ratios (OR) were calculated. Results: A total of 60,726 patients diagnosed with PANDO were included. The average age of PANDO patients was 63 ± 18 years, 63% were female. Significant associations were found between PANDO and various ocular surface and eyelid conditions, including chronic conjunctivitis (OR 2.96, 95% CI [2.73–3.20]), vernal keratoconjunctivitis (OR 2.89, 95% CI [2.45–3.29]), and blepharitis (OR 2.75, 95% CI [2.68–2.83]). There was a significant association with various upper airway conditions, including rhinitis (OR 1.62, 95% CI [1.58–1.66]), chronic sinusitis (OR 1.71, 95% CI [1.62–1.80]), and deviated nasal septum (OR 1.76, 95% CI [1.69–1.84]). Association was also observed with systemic conditions, including asthma (OR 1.34, 95% CI [1.27–1.41]) and atopic dermatitis (OR 1.36, 95% CI [1.32–1.41]). Conclusion: Ocular surface, eyelid, upper airway, and systemic inflammatory-related diseases were found to be associated with PANDO, supporting the theory that inflammation has a prominent role in the pathophysiology of PANDO. [ABSTRACT FROM AUTHOR]

A 33-year-old lady was referred to our clinic with a history of left upper eyelid swelling and difficulty to open her left eye for more than 4 years. Her globe was in infero-nasal displacement, and ocular movement was not full, with restriction to every direction. No clinical sign including eye redness, pain or visual loss was found on examination. Exophthalmometry confirmed 2 mm of left-sided proptosis. Computed tomography (CT) imaging of the orbit obtained in axial and coronal planes depicted an irregular and heterogeneous soft-tissue density mass in the left lacrimal gland, measuring 25 × 17 mm. Magnetic resonance imaging (MRI) revealed the mass of slightly longer T1 and slightly longer/shorter T2 signal, and Gd-enhanced MRI showed a significant enhancement. The tumor was first presumably diagnosed of pleomorphic adenomas. A surgery was applied to remove the tumor completely. Histopathological evaluation led to the diagnosis of PEComa. [ABSTRACT FROM AUTHOR]

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly recognised adult-onset multisystem autoinflammatory disease caused by a somatic mutation in the UBA1 gene in myeloid or erythroid precursor cells. This report describes an atypical presentation of recurrent dacryoadenitis associated with VEXAS syndrome and provides a review of the literature. A 68-year-old male presented with three episodes of unilateral alternating dacryoadenitis followed by bilateral involvement over a 4-year period. Each episode of orbital inflammation was characterised by upper lid swelling, oedema and enlarged lacrimal glands. In addition, he experienced intermittent flares of angioedema-like lesions involving the face and extremities, recurrent jaw aches, rash, progressive pulmonary fibrosis, and myelodysplastic syndrome. His inflammatory symptoms lessened with prednisolone but were refractory to methotrexate. Mycophenolate was subsequently trialled with a reasonable clinical response. Genetic testing established the diagnosis of VEXAS syndrome and tofacitinib, a JAK inhibitor, was commenced with resolution of inflammatory symptoms. [ABSTRACT FROM AUTHOR]

To provide a major review on the applications of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in evaluating orbital lesions. This review also outlines selected scenarios where DCE-MRI may be helpful. A comprehensive retrospective literature review of all English language publications on PubMed, EMBASE, and Google Scholar between 1994 and 2022. This literature review examined the specific applications and clinical scenarios surrounding the utility of DCE-MRI in orbital lesions and various findings that have been presented in the current literature. DCE-MRI provides information on tissue physiology and permeability, beyond the anatomical features displayed on static imaging. Various measured parameters (qualitative, semi-quantitative, and quantitative) obtained by DCE-MRI have been used to differentiate between benign and malignant lesions, specific orbital lymphoproliferative diseases (OLPD), lacrimal gland lesions, and various rare orbital tumours. DCE-MRI has a limited role as an initial diagnostic imaging modality. However, DCE-MRI may prove to have benefit in predicting and monitoring treatment response in orbital lymphoma as a critical imaging study, but literature specific to orbital malignancies remains limited. The value of DCE-MRI may be in situations of diagnostic uncertainty, where it may be an additional imaging aid following conventional imaging techniques. It may also act as a critical imaging modality for monitoring of orbital tumour treatment response, but the literature remains limited. Standardisation of imaging protocol, measured parameters, and statistical analysis remain limitations of this imaging technique. [ABSTRACT FROM AUTHOR]

Branching morphogenesis is a complex process shared by many organs including the lungs, kidney, prostate, as well as several exocrine organs including the salivary, mammary and lacrimal glands. This critical developmental program ensures the expansion of an organ's surface area thereby maximizing processes of cellular secretion or absorption. It is guided by reciprocal signaling from the epithelial and mesenchymal cells. While signaling pathways driving salivary gland branching morphogenesis have been relatively well-studied, our understanding of the underlying transcriptional regulatory mechanisms directing this program, is limited. Here, we performed in vivo and ex vivo studies of the embryonic mouse submandibular gland to determine the function of the transcription factor ΔNp63, in directing branching morphogenesis. Our studies show that loss of ΔNp63 results in alterations in the differentiation program of the ductal cells which is accompanied by a dramatic reduction in branching morphogenesis that is mediated by dysregulation of WNT signaling. We show that ΔNp63 modulates WNT signaling to promote branching morphogenesis by directly regulating Sfrp1 expression. Collectively, our findings have revealed a novel role for ΔNp63 in the regulation of this critical process and offers a better understanding of the transcriptional networks involved in branching morphogenesis. [ABSTRACT FROM AUTHOR]

Background: A common complication of bicanalicular intubation is dislocation of the silicone tube. Methods: Eleven patients with prolapsed silicone tubes who had undergone bicanalicular nasal intubation were injected with a 2 per cent lidocaine solution to infiltrate the lacrimal duct mucosa. A memory wire probe was used to pull a 4-0 suture through the lacrimal passage retrogradely, allowing the suture to grab the silicone tube. Paraffin oil was applied to the contact part of the rope and the silicone tube, then the distal end of the silk thread was removed from the nostril until the tube was pulled into place. Results: The prolapsed silicone tubes were restored by surgery in nine patients, with the drainage tube in the correct position in the eye and the lacrimal duct irrigation unobstructed. Conclusion: The optimisations made in this study are considered effective adjustments of reduction surgery for a prolapsed silicone tube. [ABSTRACT FROM AUTHOR]

Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix (ECM) destruction within the salivary and lacrimal glands, followed by immune cell infiltration. In this review, we have assessed the current understanding of epithelial–mesenchymal transition (EMT)-associated changes within the salivary epithelium potentially involved in salivary dysfunction and SjD pathogenesis. We performed a PubMed literature review pertaining to the determination of pathogenic events that lead to EMT-related epithelial dysfunction and signaling in SjD. Molecular patterns of epithelial dysfunction in SjD salivary glands share commonalities with EMT mediating wound healing. Pathological changes altering salivary gland integrity and function may precede direct immune involvement while perpetuating MMP9-mediated ECM destruction, inflammatory mediator expression, and eventual immune cell infiltration. Dysregulation of EMT-associated factors is present in the salivary epithelium of SjD and may be significant in initiating and perpetuating the disease. In this review, we further highlight the gap regarding mechanisms that drive epithelial dysfunction in salivary glands in the early or subclinical pre-lymphocytic infiltration stages of SjD. [ABSTRACT FROM AUTHOR]

Aplasia of lacrimal and salivary glands (ALSG) is a syndromic disorder characterized by aplasia of lacrimal and salivary systems. Reported ophthalmic manifestations of ALSG include aplasia of lacrimal glands, punctal agenesis, lacrimal sac mucocele, and membranous congenital nasolacrimal duct obstruction (CNLDO). Bony CNLDO, a rare clinical entity, has not been associated with any syndromic disorder. This study investigated the relationship between genetic mutations and bony CNLDO in 3 Chinese families with ALSG. Single-center observational case study. Three Chinese families with bony CNLDO, including 7 affected and 9 healthy family members. Slit-lamp ophthalmic examination, comprehensive physical examination, orbital computed tomography (CT) imaging, cervicofacial magnetic resonance imaging, audiometry, and whole exome sequencing on periphery blood were performed. Variants were cross-referenced with 1000 control genomes and various population databases. Pathologic variants were identified using bioinformatic tools. Clinical examination, diagnostic imaging, whole exome sequencing, and bioinformatic analysis findings. Affected patients showed decreased tear production on the Schimer I test and reduced tear breakup time. Bony CNLDO was observed on CT, showing unilateral or bilateral bony termination at the middle or terminal segment of the nasolacrimal canal. Magnetic resonance imaging showed aplasia or absence of lacrimal, parotid, and submandibular glands. Physical examination revealed normal ears, digits, and facial morphology. Audiometry and dental assessment were conducted on the pediatric patients and yielded normal results. The clinical characteristics of patients aligned with a diagnosis of ALSG. Genomic analysis revealed 3 novel heterozygous missense mutations of the Fgf10 gene: c.316T→C, c.327C→G, and c.332T→G. The inheritance pattern was autosomal dominant with variable penetrance. These variants were not observed in 1000 control genomes and population databases. These variant positions also were shown to be highly conserved across various animal species. Mutated genes and proteins were predicted as deleterious with most computational models, with a few suggesting they may be benign. Bony CNLDO was identified as a novel phenotype of ALSG implicated by missense mutations of highly conserved residues in the Fgf10 gene. These cases broadened our knowledge of Fgf10 -related phenotypes and prompted clinicians to consider syndromic associations in patients with bony CNLDO. The author(s) have no proprietary or commercial interest in any materials discussed in this article. [ABSTRACT FROM AUTHOR]

Pupose: In this study, we aimed to evaluate the anatomical features of the nasolacrimal groove in detail by providing a morphological classification based on morphometric evaluations of the nasolacrimal groove. Methods: A total of 150 sagittal dry bones in the Department of Anatomy, Faculty of Medicine, Istanbul University were evaluated. The length and the width at different points of the nasolacrimal canal were calculated. According to the widths of the nasolacrimal canal ten different morphological types were revealed. Results: The length of the canal was found as mean 13.62 ± 2.42 mm on the right and 12.44 ± 2.68 mm on the left side. The entrance, the base, the upper and the lower thirds of nasolacrimal canal were 6.22 ± 1.19 mm, 7.95 ± 1.85 mm, 5.85 ± 1.06 mm, 6.60 ± 1.54 mm, on the right and 6.08 ± 1.16 mm, 7.24 ± 1.64 mm, 5.45 ± 1.29 mm, 6.23 ± 1.48 mm, on the left side, respectively. The width of the entrance of the nasolacrimal canal was the narrowest width compared to the base, upper and lower thirds in 7/10 types of 71/150 cranial bones. Conclusion: This comprehensive morphological classification of the nasolacrimal groove sheds new light on its complex variations. We support that the finding of this study has the potential to improve the precision of diagnostic assessments and guide specific therapeutic interventions for patients with lacrimal drainage disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, increasing studies have focused on the abnormal proliferation and differentiation of acinous cells in the meibomian gland, suggesting that this process is closely related to the occurrence and development of dry eye. Structural and functional abnormalities such as blockage of the lumen of the meibomian gland and atrophy of the glands can cause or exacerbate dry eye. Therefore, the study of changes in the meibomian glands in dry eyes is important for understanding the pathogenesis of dry eyes in depth and finding new targets for the treatment and prevention of dry eyes. OBJECTIVE: To investigate the changes of the meibomian gland in a mouse model of aqueous deficient dry eyes. METHODS: Thirty-two female C57/B6 mice at 6-8 weeks were selected and randomly divided into experimental and control groups with 16 mice in each group. The mice in the experimental group were constructed by removing both the extra-orbital and intra-orbital lacrimal glands, while those in the control group were not treated. After 2 weeks of normal feeding, the corneal changes of both groups were observed under a slit lamp, and the tear secretion of both groups was measured. The meibomian glands of the two groups of mice were removed after decapitation. The changes in the gross morphology of the meibomian glands were observed and the meibomian glands were made into frozen sections. Hematoxylin-eosin staining was used to observe the structure of the meibomian glands, oil red staining was used to evaluate the function of the meibomian glands, and immunofluorescence staining and RT-qPCR were used to observe the expression of cytokeratin 14, Ki67 and abnormally differentiated small proline-rich protein 1B in the meibomian glands of mice. RESULTS AND CONCLUSION: Two weeks after modeling, lamellar defects were seen in the corneas of the experimental mice, and neovascularization of the limbal corneal was generated and invaded the central cornea. (2) Tear secretion volume was significantly reduced in the experimental group compared with the control group (P < 0.05). Microscopic findings showed that the ducts of the meibomian glands in the experimental group were interrupted and atrophied, and their arrangement was disorganized. Hematoxylin-eosin staining results showed a significant increase in lipid vacuoles in the meibomian glands of the experimental mice compared with the control group. Lipid deposition was seen in oil red staining in the experimental group. Immunofluorescence and RTqPCR results showed a significant increase in the expression of cytokeratin 14, Ki67 and small proline-rich protein 1B in the meibomian glands of mice in the experimental group compared with the control group (P < 0.05). To conclude, aqueous deficient dry eye can lead to compensatory hypertrophy, increased proliferation, and abnormal lipid metabolism in the meibomian gland, as well as abnormal differentiation of the meibomian gland. [ABSTRACT FROM AUTHOR]

To analyze the clinical characteristics of mucinous obstruction diagnosed by dacryoendoscopy and compared the cytological changes with membranous obstruction using a modified liquid-based thin prep cytology method. A retrospective chart review was conducted on 53 eyes of 51 patients with mucus obstruction based on dacryoendoscopic findings from January 2022 to October 2022. Liquid-based thin-prep cytology was performed by irrigating the inside of the nasolacrimal drainage system with saline during dacryoendoscopy-guided silicone tube intubation. Pathological findings were analyzed through a comparison of mucinous obstruction with membranous obstruction as determined by dacryoendoscopic findings. The modified liquid-based thin prep cytology technique had a higher cytology detection rate across all cases. Mucinous obstruction exhibited a significantly higher number of successful canalicular irrigation test cases compared to membranous obstruction. In mucinous obstruction, epithelial squamous cells were more frequently detected in pre-sac obstruction, whereas columnar epithelial cells were predominant in post-sac obstruction. Inflammatory cells showed a stronger correlation with primary change and post-sac obstruction. Bacterial colonies were observed exclusively in cases of mucinous obstruction. The use of a modified liquid-based thin prep cytology method enables the examination of histopathological changes in the lacrimal passage in primary acquired nasolacrimal duct obstruction (PANDO), particularly in cases of mucinous obstruction, without the need for invasive biopsies. These findings enhance the understanding of the etiopathogenesis of mucinous obstruction, complementing knowledge of membranous obstruction in PANDO. [ABSTRACT FROM AUTHOR]

The lacrimal gland is crucial for maintaining ocular health by producing the aqueous component of the tear film, which hydrates and nourishes the ocular surface. Decreased production of this component results in dry eye disease, a condition affecting over 250 million people worldwide. However, the scarcity of primary human material for studying its underlying mechanisms and the absence of a cell model for human lacrimal gland epithelial cells present significant challenges. Here, we describe the generation of immortalized human lacrimal gland cell lines through the introduction of an SV40 antigen. We successfully isolated and characterized three cell clones from a female lacrimal gland donor, confirming their epithelial identity through genomic and protein analyses, including PCR, RNAseq, immunofluorescence and cultivation in a 3D spheroid model. Our findings represent a significant advancement, providing improved accessibility to investigate the molecular pathogenesis mechanisms of dry eye disease and potential therapeutic interventions. We identified the expression of typical epithelial cell marker genes and demonstrated the cells' capability to form 2D cell sheets and 3D spheroids. This establishment of immortalized human lacrimal gland cells with epithelial characteristics holds promise for future comprehensive studies, contributing to a deeper understanding of dry eye disease and its cellular mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: To describe a novel endoscopic technique to approach the maxillary sinus (MS), the Modified Anterior Medial Maxillary Approach (MAMMA), preserving the inferior turbinate (IT) and the nasolacrimal duct (NLD). To perform radiological measurements and describe a case series to study the feasibility and limits of MAMMA. Methods: Computed tomography (CT) scans (n = 150 nasal cavities) were used to calculate areas of the MAMMA to define surgical limits and extensions. Measurement of distances to critical anatomy landmarks and total area for the MAMMA were calculated. An instructional case illustrating the surgical technique and outcome was also included. Results: Radiological analysis showed a mean distance from the Piriform Aperture (PA) to the anterior limit of the NLD of 1.03 ± 0.18 cm (range 0.59–1.48) and a mean distance from de PA to the posterior limit of the NLD of 1.57 ± 0.22 cm (range 1.02–2.11). The mean distance from the nasal floor to the Hasner's valve was 1.61 ± 0.27 cm (range 1.06–2.52) and the distance from the nasal floor to the insertion of the IT was 2.20 ± 0.36 cm (range 1.70–3.69). Finally, the mean total area for the MAMMA was 4.04 ± 0.52 cm2 (range 3.17–5.53). No complications or recurrence of the pathology were observed in operated patients. Conclusion: The MAMMA provides a wide surgical field of the MS walls comparable to more aggressive techniques, with preservation of the sinonasal and lacrimal function. MAMMA is an effective alternative to treat different MS pathologies including benign recurrent maxillary sinus tumors. [ABSTRACT FROM AUTHOR]

To evaluate the outcome and complications of Endoscopic endonasal Dacryocystorhinostomy (DCR) using an inferiorly based mucosal flap as compared to a conventional posteriorly based mucosal flap with flap preservation and no stenting. 36 patients presenting with nasolacrimal duct obstruction were divided into two groups: the first group underwent endoscopic DCR using an inferiorly based mucosal flap, and the other group used a posteriorly based mucosal flap. In both groups, the mucosal flap was preserved, and bone was removed using Kerrison's punch. No stenting was done in any of the cases. The patency of the ostia was determined by syringing, and nasal endoscopy was done to look at the neo-ostium at follow-up visits to determine success and complications in each group. All 18 cases in the inferiorly based flap group had patent ostia with good mucosalization of the neo-ostium at 6-month follow-up. 3 of the 18 cases in the conventional posteriorly based flap group had failure due to granulation tissue formation around the neo-ostium. The use of an inferiorly based mucosal flap is easy to fashion and reposition at the end of the surgery. This technique has a good outcome with patent ostia during the follow-up period of 6 months. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) of the lacrimal gland is the most common malignant epithelial tumor of the lacrimal gland. The biological behavior of these tumors is characterized by a slow growth with frequent nerve invasion but rare invasion of the neck nodes. Local extension intracranially with bone erosions is seen in locally advanced tumors. Distant metastasis to lungs bone and liver are commonly reported. Treatments using surgery and radiotherapy are generally preferred for adequate tumor control. However there is still no consensus on the best treatment approach. [ABSTRACT FROM AUTHOR]

Of all the head and neck tumors, salivary gland tumors account to 3%. Pleomorphic adenomas are one of the most common benign tumors arising from major salivary glands, although it could also develop from minor salivary glands situated at accessory sites like nasal cavity, pharynx, parapharyngeal space, lacrimal glands etc. Tumors of infratemporal fossa are quite unusual, mainly because of its hidden location in retromaxillary region. We report an unusual case of 65 years old male presenting with complaint of progressive left cheek swelling for 4 years. FNAC revealed pleomorphic adenoma of minor salivary gland tumor. Intraoperatively a giant lobulated tumor was seen occupying almost whole space of infratemporal fossa, which was removed in-toto via open approach. Patient was kept on regular follow up with no evidence of recurrence reported till date. [ABSTRACT FROM AUTHOR]

Primary Mucinous eccrine carcinoma (MEC) is a rare malignant neoplasm of skin believed to arise from eccrine sweat gland commonly with periocular involvement. Here we report a case of 60-year male with a recurrence of unilateral nasomaxillary mass and epiphora. Imaging suggested nasolacrimal duct as probable site of origin. Histopathology and immunochemistry confirmed the diagnosis and managed surgically. This case report emphasizes the significance of including primary MEC in the differential diagnosis of nasomaxillary mass for its recurrence nature and histological similarity with metastasis from other viscera. [ABSTRACT FROM AUTHOR]

Open imaging fluorescence devices have been utilized in surgical oncology, vascular and plastic surgery; however, the role of indocyanine green (ICG) in periorbital surgery and lymphatics has not been explored. A prospective, single-center diagnostic study was conducted from 2021 to 2022 utilizing ICG to assess both the periorbital vasculature and lymphatics. Fluorescence was captured with open-imaging fluorescent devices. For ICG angiography, a total of 5–10 mg of ICG was given intravenously at various time points to visualize intraoperative blood flow to eyelid flaps, vascular tumors, or extraocular muscles. For ICG lymphography, 0.03–0.06 mg of ICG was injected subcutaneously to visualize the periorbital and facial lymphatic drainage. Twenty-two patients underwent ICG angiography. Periorbital vascular supply was seen in eyelid reconstructions (n = 8), anophthalmic reconstructions (n = 2), lacrimal gland tumors (n = 2), orbital venous malformations (n = 2), tumor metastasis (n = 1) and benign tumors (n = 1). The anterior ciliary arteries were visualized to the extraocular muscles in fracture repairs (n = 3) and muscle biopsies (n = 2). Ten patients underwent ICG lymphangiography highlighting the global periorbital lymphatic system. ICG allows for visualization of the vasculature of extraocular muscles and tumors, assessing perfusion of flaps during reconstruction and the global periorbital lymphatic drainage pathways. [ABSTRACT FROM AUTHOR]

A pilot study to identify bacterial biofilm in the lacrimal sacs of patients with chronic dacryocystitis, and in patients with epiphora but without discharge, using scanning electron microscopy. Five patients: two with nasolacrimal duct obstruction without dacryocystitis, and three with dacryocystitis refractory to antibiotics, underwent external dacryocystorhinostomy. One control patient without infection was included. Bacterial cultures were obtained from the lumen of the lacrimal sac to analyze possible bacterial growth, including antibiotic resistance. Biopsies were taken from all lacrimal sacs and prepared for light and scanning electron microscopy. Scanning electron microscopy of all the lacrimal sac samples revealed structures consistent with bacterial communities and adjacent extracellular material, indicating biofilm formation. This was most prominent in one of the patients with chronic dacryocystitis. Bacteria were found not only on the luminal surface of the sac, but also within the tissue of the sac. Bacterial growth was identified in samples from two patients with chronic dacryocystitis, whereas samples from the other three patients showed no bacterial growth. Lack of patency of the lacrimal duct predisposes to bacterial growth, even in patients with no clinically confirmed infection of the lacrimal sac. The finding of a biofilm in patients with chronic dacryocystitis explains the lack of efficiency of antibiotic treatment at the concentrations used in clinical practice. [ABSTRACT FROM AUTHOR]

The aim is to increase the understanding of lacrimal gland pleomorphic adenoma's recurrence rate and the factors that influence it. A systematic search of PubMed, SCOPUS, Cochrane Library, and CINAHL was conducted following PRISMA guidelines. The data in the included studies were extracted and analyzed. Twenty-two studies were included representing 963 patients from 12 different countries. The pooled analysis of the recurrence rate was 8.83% (95% CI: 5.08–13.50). In the event of recurrence, there was a 75.17% (95% CI: 65.98–82.94) chance of benign recurrence and a 28.35% (95% CI: 19.66–38.41) chance of malignant recurrences, with malignant recurrence occurring almost exclusively after a benign recurrence. The results showed that 47.09% (95% CI: 24.60 to 70.22) of recurrent tumors had a ruptured pseudocapsule and 6.35% (95% CI: 0.82 to 16.54) had an intact pseudocapsule with a significant difference between the two. Of the recurrent tumors, 51.50% (95% CI: 9.28 to 92.39) were biopsied compared to 8.83% (95% CI: 3.40 to 16.49) of the total; the difference between these two proportions was also found to be significant. There was a statistically significant difference in the rates of recurrence between tumors that were either biopsied or had a ruptured pseudocapsule compared to those that did not. This evidence adds additional support for excisional biopsy being the procedure of choice for LGPA and reinforces the importance of keeping the pseudocapsule intact during surgical resection. [ABSTRACT FROM AUTHOR]

To study the efficacy of cyclosporin 0.05% eye drops in the management of grade 1 and 2 acquired punctal stenosis and to compare the results with the clinical outcomes of mini-Monoka insertion. A prospective, controlled, interventional clinical study includes all patients (16 years and older) with symptomatic epiphora and diagnosed with grade 1 or grade 2 acquired punctal stenosis. All patients undergo punctal dilatation, canalicular probing, and nasolacrimal duct irrigation. Afterwards, patients are divided into two groups: Group A: patients receive only medical treatment in the form of topical 0.05% cyclosporin (Restasis®, Allergan Inc.) twice daily for 6 months. Group B: patients receive mini-Monoka stent insertion in the lower canaliculus for 6 weeks. Outcome measures are changes in Munk scoring, grading of the punctum, and functional and anatomical success. Functional success is defined as Munk score 0 to 1 and FDDT grade 0–2. Anatomical success is defined as grade 3 punctum. Forty-two patients are included in the study, with 21 patients in each group. There were no significant differences in the Munk score between the two groups before treatment; however, group B had a significantly higher mean rank at 6 months after treatment. After treatment, the punctal size was significantly larger in group B at 4 weeks and 3 months. However, no significant difference in punctal size was detected at 6 months after treatment between the two groups. Application of cyclosporin 0.05% eye drops is a simple and efficient non-interventional method in the management of grade 1 and 2 acquired punctal stenosis. [ABSTRACT FROM AUTHOR]

The current case presentation highlights the potential of cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, as first-line treatment for periocular metastatic cutaneous squamous cell carcinoma (SCC) without requiring curative surgery or radiotherapy. A 64-year-old male presented with a progressing 4.5 × 3.0 cm left upper eyelid lesion initially diagnosed as psoriasis. Work-up revealed cutaneous SCC with tumor invasion into extraconal fat and lacrimal gland, and metastasis to the left parotid lymph node. The patient also presented with a suspicious lesion on his left medial thigh found to be a second primary on pathology. To avoid orbital exenteration and treat the multifocal disease, the patient was started on intravenous cemiplimab immunotherapy. Following six doses, repeated FGD-PET-CT revealed a complete response of the left eyelid lesion and residual low-grade hypermetabolic activity of the left medial thigh lesion. Biopsy confirmed chronic inflammation and fibrosis with no signs of malignancy. This unique case with dual primary cutaneous SCC provides support for cemiplimab in treating locally invasive periocular SCC, and potentially abrogating the need for highly morbid exenteration procedures to preserve binocular vision. [ABSTRACT FROM AUTHOR]

A 14-year-old female presented with 2 weeks of progressive right eye pain, erythema, and proptosis. Examination demonstrated an enlarged palpable mass along the right superior lateral orbit and bilateral conjunctival petechiae. Of note, she was asymptomatic on the left side, and the petechiae were present only on the superior bulbar conjunctiva with eyelid eversion. Imaging demonstrated bilateral lacrimal gland enhancement. Testing was significant for elevated inflammatory markers, but otherwise negative workup. Biopsy of the right lacrimal gland demonstrated acute-on-chronic inflammation without evidence of lymphoproliferative disease. On repeat testing, myeloperoxidase antibody levels (MPO/p-ANCA) were elevated, indicative of an underlying immune-mediated vasculitis. This case illustrates a rare presentation of ANCA-associated vasculitis in a pediatric patient. It further demonstrates the phenomenon of initial negative serology and subsequent auto-antibody seroconversion in a patient with localized granulomatosis with polyangiitis. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common and frequent ocular surface disease worldwide, which can cause severe ocular surface discomfort and blurred vision. Inflammation and reactive oxygen species (ROS) play decisive roles in the development of DED. However, existing treatments usually focus on anti-inflammation while ignore the role of ROS in DED. Ever worse, the clinical preparations are easily cleared by nasolacrimal ducts, resulting in poor therapeutic effect. To circumvent these obstacles, here we designed a phenylboronic acid (PBA) modified liposome co-loading immunosuppressant cyclosporin A (CsA) and antioxidant crocin (Cro). The CsA/Cro PBA Lip achieved mucoadhesion through the formation of covalent bonds between PBA and the sialic acid residues on mucin, and consequently improved the retention of drugs on the ocular surface. By inhibiting ROS production and blocking NF-κB inflammatory pathway, CsA/Cro PBA Lip successfully promoted the healing of damaged corneal epithelium, eventually achieving the goal of relieving DED. CsA/Cro PBA Lip is proven a simple yet effective dual-drug delivery system, exhibiting superior antioxidant and anti-inflammatory effects both in vitro and in vivo. This approach holds great potential in the clinical treatment of DED and other related mucosal inflammations. [Display omitted] • PBA modification prolongs the retention time of liposome on the ocular surface. • Synergistic anti-inflammatory and anti-oxidant strategy for better efficacy. • The mucoadhesive dual-drug delivery system significantly alleviates DED. [ABSTRACT FROM AUTHOR]

Background: Anti-glaucoma eye drops have been investigated due to their production of fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal drainage system. We aimed to assess whether these effects may impair the effectiveness of endoscopic endonasal dacryocystorhinostomy (EE-DCR). Methods: This is a single-center observational retrospective study on EE-DCR via a posterior approach. Resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Results: Twenty patients (32 sides) were enrolled. Preoperatively, 93.75% (n = 30/32) presented severe (Munk 3–4) epiphora and 68.75% (n = 22/32) recurrent dacryocystitis. At T1, 50.0% (n = 16/32) were referred with residual epiphora (Munk ≥ 1) and 18.75% (n = 6/32) dacryocystitis. At T2, 31.25% (n = 10/32) still complained of epiphora (Munk ≥ 1) and 6.25% (n = 2/32) dacryocystitis. Difference of outcomes at aggregate and paired timepoints (except for T1 versus T2) resulted in statistical significance (p < 0.05). At T2, 22 (68.75%) complete, 8 (25.0%) anatomical successes and 2 (6.25%) surgical failures were observed. Conclusions: Despite the chronic uptake of anti-glaucoma eye drops, EE-DCR guaranteed high rates of clinical relief from epiphora and remarkable decreases in the rates of recurrent dacryocystitis. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is a common chronic autoimmune disease that manifests as dry mouth, dry eyes and systemic complications. There are sex differences in the clinical manifestations between men and women, with the average age of onset being around 55 years and the majority of female patients developing the disease during the menopausal years. Understanding the impact of sex differences on SS may help in the treatment and prognosis of patients. Studies have confirmed that a number of factors are associated with the onset of SS, but the exact mechanisms are not fully understood. Sex hormones (especially oestrogens and androgens) play a very important role, and the balance of sex hormone levels in the body is crucial for maintaining homeostasis in the acinar cells of the lacrimal and salivary glands. In addition, chromosomes play a very important role in the sex differences in SS. The gut microbiota also has some influence on sex differences in SS. In this review, we focus on oestrogens and androgens, which are important in the pathogenesis of SS, and summarize the progress of non‐clinical studies. Sex differences may influence differences in individualized treatment regimens and further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder characterized by organ-specific symptoms in the salivary and lacrimal glands, as well as systemic manifestations. Fatigue, a prominent aspect, significantly influences the overall quality of life for individuals with pSS. Methods: This review seeks to evaluate the impact of fatigue by exploring its consequences, potential causes, and effects on physical and psychological well-being, while also investigating its management strategies. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Initially identifying 78 articles in reputable international medical databases, we applied eligibility criteria and removed duplicates, resulting in 19 articles for qualitative synthesis. Results: This review delves into the predictive factors for heightened fatigue in pSS, encompassing rheumatoid factor levels, erythrocyte sedimentation rate, and immunoglobulin G levels. Sleep disturbances, specifically nighttime pain and nocturia, emerged as determinants of persistent daytime fatigue. Cognitive impairment in pSS involves deteriorations in global memory, executive functioning, and attentional resources. Furthermore, functional limitations in pSS impact patients' quality of life. Conclusions: The significance of fatigue in pSS, its consequences, and profound influence on the quality of life necessitate further research for a more comprehensive understanding of this complex issue. [ABSTRACT FROM AUTHOR]

Simple Summary: The corneal epithelium is a protective barrier and refractive structure in the eye maintained through a complex regenerative process involving the lacrimal gland, tear film, and corneal nerves. This review explores the insulin-like growth factor (IGF) system and its role in corneal epithelium homeostasis. Emphasis is placed on the significance of limbal epithelial stem cells and potential therapeutic applications targeting the system components. The corneal epithelium, comprising three layers of cells, represents the outermost portion of the eye and functions as a vital protective barrier while concurrently serving as a critical refractive structure. Maintaining its homeostasis involves a complex regenerative process facilitated by the functions of the lacrimal gland, tear film, and corneal nerves. Crucially, limbal epithelial stem cells located in the limbus (transitional zone between the cornea and the conjunctiva) are instrumental for the corneal epithelium integrity by replenishing and renewing cells. Re-epithelialization failure results in persistent defects, often associated with various ocular conditions including diabetic keratopathy. The insulin-like growth factor (IGF) system is a sophisticated network of insulin and other proteins essential for numerous physiological processes. This review examines its role in maintaining the corneal epithelium homeostasis, with a special focus on the interplay with corneal limbal stem cells and the potential therapeutic applications of the system components. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, tissue infiltration of IgG4-positive cells, and fibrosis. Although a number of IgG4-RD patients show sinonasal involvement, there is little known about sinonasal inflammation associated with IgG4-RD. This study aimed to describe the clinicopathological features of sinonasal inflammation associated with IgG4-RD and to compare with other inflammatory diseases, such as eosinophilic chronic rhinosinusitis (ECRS) and granulomatosis with polyangiitis (GPA). Methods: A retrospective analysis of clinicopathological features of patients with sinonasal lesions and high serum IgG4 was performed. Patient data were reviewed to determine whether they fulfilled the diagnostic criteria for other inflammatory diseases. Results: Six of 7 patients were diagnosed with IgG4-RD, while 1 patient was diagnosed with GPA. In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and nasal crusting in the 3 patients (50%). Computed tomography showed ethmoid sinus involvement in 5 patients (83%). Five of the 6 patients (83%) were diagnosed with IgG4-RD based on nasal biopsy, whereas 1 patient (17%) was diagnosed based on lacrimal gland biopsy. Four patients fulfilled the Japanese epidemiological survey of refractory ECRS (JESREC) criteria. However, none of the patients showed eosinophil infiltration. Although the patient with GPA showed high levels of serum IgG4 and tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient showed common clinical features of GPA. Conclusion: Patients with sinonasal inflammation associated with IgG4-RD had similar clinical characteristics with ECRS and GPA. Histopathological findings of the nasal biopsy from clinically diagnosed GPA was consistent with that of IgG4-RD. Sinonasal inflammation associated with IgG4-RD should be diagnosed based not only on tissue infiltration of IgG4-positive cells but in conjunction with clinical findings such as local nasal characteristics, involvement of other organs, and serum antineutrophil cytoplasmic antibody levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration. Plain Language Summary: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related Disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that affects multiple organs, resulting in tumefactive lesions and/or organ dysfunction. This chronic, multiorgan inflammatory process is characterised by the infiltration of IgG4-positive plasma cells and has a variable clinical presentation depending on the organ involved. The present case series discusses four cases (two males and two females) of IgG4-RD involving different sites in patients presented to present Institution. The authors reviewed four cases of IgG4-RD, including clinical details, biochemical, radiological, and histopathological features. The case series includes IgG4-RD masquerading as meningioma, IgG4-related sclerosing cholangitis, IgG4-RD of the thyroid gland, and IgG4-RD of the lacrimal gland. Since IgG4-RD has non specific clinical features, histopathological analysis and immunohistochemistry play a pivotal role in diagnosis. Despite its diagnostic difficulties, earlier recognition is crucial to prevent significant morbidity and extensive fibrosis leading to organ failure. [ABSTRACT FROM AUTHOR]

Graft‐versus‐host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments. [ABSTRACT FROM AUTHOR]

Adult stem cells, present in various parts of the human body, are undifferentiated cells that can proliferate and differentiate to replace dying cells within tissues. Stem cells have specifically been identified in the cornea, trabecular meshwork, crystalline lens, iris, ciliary body, retina, choroid, sclera, conjunctiva, eyelid, lacrimal gland, and orbital fat. The identification of ocular stem cells broadens the potential therapeutic strategies for untreatable eye diseases. Currently, stem cell transplantation for corneal and conjunctival diseases remains the most common stem cell‐based therapy in ocular clinical management. Lens epithelial stem cells have been applied in the treatment of paediatric cataracts. Several early‐phase clinical trials for corneal and retinal regeneration using ocular stem cells are also underway. Extensive preclinical studies using ocular stem cells have been conducted, showing encouraging outcomes. Ocular stem cells currently demonstrate great promise in potential treatments of eye diseases. In this review, we focus on the identification, characterisation, and therapeutic application of adult stem cells in the eye. [ABSTRACT FROM AUTHOR]

Purpose: Topical antihistamines, such as olopatadine hydrochloride, an H1 receptor antagonist, are commonly prescribed for treating allergic conjunctivitis. Drug delivery via eye drops has many deficiencies including a short residence time due to tear drainage via the nasolacrimal duct, which results in a low bioavailability and potential for side effects. These deficiencies could be mitigated by a drug-eluting contact lens such as the recently approved ACUVUE® THERAVISION™ WITH KETOTIFEN which is a daily disposable etafilcon, a drug-eluting contact lens with ketotifen (19 μg per lens). Here, we investigate the feasibility of designing a drug-eluting lens with sustained release of olopatadine for treating allergies using an extended wear lens. Methods: Nanobarrier depots composed of vitamin-E (VE) are formed through direct entrapment by ethanol-driven swelling. The drug-loaded lenses are characterized for transparency and water content. In vitro release is measured under sink conditions and fitted to a diffusion control release model to determine diffusivity and partition coefficient. Results:In vitro studies indicate that ACUVUE OASYS® and ACUVUE TruEye™ lenses loaded with ∼0.3 g of VE/g of hydrogel effectively prolong olopatadine dynamics by 7-fold and 375-fold, respectively. Incorporation of VE into the lenses retains visible light transmission and other properties. Conclusion: The VE incorporation in commercial lenses significantly increases the release duration offering the possibility of antiallergy extended wear lenses. [ABSTRACT FROM AUTHOR]

To establish the diagnostic value of the quantitative parameters of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) combined with conventional MRI in differentiating of benign and malignant lacrimal gland epithelial tumours. A retrospective analysis of primary lacrimal gland epithelial tumours confirmed by histopathology was conducted. Conventional MRI features and DCE-MRI quantitative parameters were collected and subjected to analysis. The diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis. A total of 53 patients were enrolled of which 29 had malignant, whereas 24 had benign tumours. Conventional MRI revealed statistically significant differences between benign and malignant tumours regarding maximum tumour diameter, posterior margin characteristic, bone destruction, and erosion. The Ktrans and K ep values obtained by DCE-MRI were higher in malignant than in benign tumours, with a statistically significant (p< 0.001 and p= 0.022). A type I time–signal intensity (TIC) curve was more frequent in benign tumours, whereas a type II TIC curve was prevalent in malignant tumours (p= 0.001). ROC analysis showed that Ktrans had the best diagnostic value of the DCE-MRI parameters (area under the ROC curve [AUC] of 0.822, 75.9% sensitivity, and 83.3% specificity, p< 0.001). The combination of conventional MRI and DCE-MRI factors had the best diagnostic value and balanced sensitivity and specificity (AUC of 0.948, 93.1% sensitivity, and 91.7% specificity, p< 0.001). The present findings indicate that the combination of quantitative parameters of DCE-MRI and image characteristics of conventional MRI have a high diagnostic value for the diagnosis of benign and malignant lacrimal gland epithelial tumours. • Conventional MRI features had higher diagnostic specificity. • DCE-MRI quantitative parameters had higher diagnostic sensitivity. • The combination showed the best diagnostic value. [ABSTRACT FROM AUTHOR]

Purpose: To compare endonasal dacryocystorhinostomy (EN-DCR) with sheath-guided dacryoendoscopic probing and bicanalicular intubation (SG-BCI) by evaluating tear meniscus area (TMA) and total high-order aberrations (HOAs) for primary acquired nasolacrimal duct obstruction (PANDO). Method: We retrospectively reviewed 56 eyes of 42 patients (7 men, 35 women; age, 72.7±13.1 years) who underwent EN-DCR or SG-BCI for PANDO in Toyama University Hospital from February 2020 to June 2022. In the EN-DCR and SG-BCI groups, we measured the patency of the lacrimal passage, preoperative and postoperative TMA, and HOAs of the central 4 mm of the cornea using optical coherence tomography (AS-OCT), six months postoperatively. Results: There was a positive correlation between preoperative TMA and preoperative HOAs in all cases. Postoperative patency of lacrimal passage was 100% in the EN-DCR and 80.8% in the SG-BCI group. There was a significant difference in the number of passages between the two groups (p = 0.01). Preoperative TMA and HOAs showed a significant postoperative decrease in both groups (EN-DCR group: p<0.01, p<0.01, SG-BCI group: p<0.01, p=0.03, respectively). We then calculated the rate of change of preoperative and postoperative TMA and HOAs and compared them between the two groups. The rate of change was significantly higher in the EN-DCR group than that in the SG-BCI group (TMA, p=0.03; HOAs, p=0.02). Conclusion: Although both EN-DCR and SG-BCI are effective for PANDO, our results suggest that EN-DCR is more effective in improving TMA and HOAs. [ABSTRACT FROM AUTHOR]

Background: Pilocarpine HCl is a non-selective muscarinic receptor agonist that is prescribed for the treatment of glaucoma. The use of pilocarpine conventional eye drops is associated with several side effects, such as loss of visual acuity, and the need for several applications due to rapid drainage away via the nasolacrimal duct, especially for elderly people. Such adverse effects can lead to low patient compliance and poor clinical outcomes. Therefore, the aim of this project was to develop, optimise and characterise a biodegradable pilocarpine HCl ocular insert using niosomes as a drug delivery vehicle. To achieve that, various polymers such as hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), and a blend of both were investigated to prepare the ocular inserts using solvent casting technique. The niosomes of pilocarpine HCl were prepared using span-60 and cholesterol by thin film hydration method. The produced noisome-loaded ocular inserts were characterised using various analytical techniques, including Fourier Transform Infrared (FTIR), X-ray Diffractions (XRD), thermal analysis, particle size analysis, weight and content uniformity, surface pH and drug release profile, among others. Results: The results indicated that drug-free ocular inserts of the two polymers (HPMC + PVA) were better than single polymer-based ocular inserts (HPMC or PVA alone). The formed niosomes demonstrated good entrapment efficiency of 49.7% ± 7.0, with an average particle size of 325.7 ± 3.5 nm. The FTIR analysis showed no interaction between the compositions of niosomes. Four optimal formulations with various co-polymer ratios and pilocarpine content were further evaluated. Pilocarpine-containing niosomes-loaded ocular inserts provided uniformity in pilocarpine content (89–96%), with 34.8% moisture content and an average pH of 7. The release profile of niosomes-loaded inserts demonstrated an initial burst release within 2 h ranging from 26.54% (T4) to 41.22% (T2), and continuous sustained release for the next 24 h (68.32 ± 5.11% (T4) to 82.11 ± 6.01% (T2)). Conclusions: This work successfully optimised biodegradable ocular inserts containing slow-release pilocarpine HCl encapsulated in niosomes for the treatment of glaucoma without dose dumping, resulting in a user-friendly drug delivery system. [ABSTRACT FROM AUTHOR]

Patient: Male, 7-month-old Final Diagnosis: Coloboma • congenital • eyelid Symptoms: Defect • lagophthalmos Clinical Procedure: -- Specialty: Ophthalmology Objective: Congenital defects/diseases Background: Congenital eyelid coloboma in children often faces complications such as keratitis, symblepharon, and amblyopia. Repairing defects involving at least 50% of the eyelid margin can be challenging. Acellular dermal allograft (ADA) has achieved excellent results as a substitute in adult eye plastic surgery, with minimal morbidity. This report describes a case of reconstruction of an eyelid defect in a 7-month-old male infant using an ADA. Case Report: A 7-month-old male infant was referred due to congenital eyelid coloboma in the left eye, which affected nearly one-half of the upper and lower eyelids medially, with more than 9 mm of lagophthalmos and lacrimal duct malformation inducing dacryocystitis. Under general anesthesia, A U-shaped silicone drainage tube was inserted in the nasolacrimal duct to ensure an unobstructed lacrimal duct. The symblepharon release, pseudopterygium excision, and medial canthus reconstruction were performed sequentially. Then, the upper eyelid defect was repaired through the advancement of the lateral segment of the eyelid, following lateral cantholysis. A trimmed ADA was placed as a substitute for the tarsal plate in the lower eyelid defect area and sutured with the free edge of the retractor. Finally, the lower and lateral skin orbicular muscle flap was advanced to cover the acellular dermis composite graft. The postoperative eyelid morphology was satisfactory. At 6 months after surgery, lower eyelid retraction gradually appeared. Conclusions: ADA is presented as an effective solution for reconstructing significant eyelid defects of infants. However, the potential of postoperative eyelid retraction still deserves future research and refinement in surgical techniques. [ABSTRACT FROM AUTHOR]

Malignant melanoma of the conjunctiva is a rare tumor of the ocular surface with potential fatal consequences and a high likelihood of recurrence. Although routes for extending the tumor, including local, hematogenous, and lymphatogenous, are pretty straightforward, the indirect extension through free-floating tumoral cells to the nasolacrimal duct is not described thoroughly. We report a case of malignant melanoma of the conjunctiva which presented with local recurrence in the intranasal cavity and lacrimal sac two years after the primary surgery (without involvement of the ocular surface and punctum on the second occasion). However, there was no evidence of distant metastasis on either occasion. This case demonstrates the possible noncontiguous spreading route of melanoma tumoral cells and highlights the need for attention to the surgical technique, and careful follow-up to detect further disease activity. [ABSTRACT FROM AUTHOR]