[Cell technologies as a basis for the development of regenerative principles for the treatment of lacrimal gland diseases]. / Kletochnye tekhnologii kak osnova razrabotki regeneratornykh printsipov lecheniya zabolevanii sleznoi zhelezy.

The lacrimal gland (LG) is a tubuloacinar exocrine gland composed of acinar, ductal, and myoepithelial cells. Three-dimensional distribution of acinar lobules, ducts, and myoepithelial cells is necessary for the effective functioning of the organ. LG is the main organ of immune surveillance of the ocular surface system. The embryogenesis of the gland is regulated by the interaction of genetic mechanisms, internal epigenetic (enzyme systems, hormones) and exogenous factors. There is no doubt that there is a clear genetic program for the implementation of the complex process of embryonic development. The mechanisms regulating LG organogenesis initiate the work of a huge number of structural oncogenes, transcription and growth factors, etc. Studying the expression and selective activity of regulatory genes during organ development, their participation in the differentiation of different cell types is a current trend at the nexus of clinical genetics, molecular biology, embryology and immunocytochemistry. Due to its relatively simple structure and accessibility, human LG is a suitable object for potential application in regenerative medicine. Development of a universal protocol for obtaining functional differentiated secretory epithelium of LG capable of expressing tissue-specific markers is an urgent task. Determining the nature and origin of stem cells and progenitor cells will allow the isolation and multiplication of these cells in culture. After obtaining a functionally active culture of LG cells, it is possible to create a model of autoimmune diseases.

Post-traumatic canalicular fistula: description and review of literature - SALDO update study (SUP) - paper II.

PURPOSE: To discuss the clinical spectrum and management strategies in patients with post-traumatic canalicular fistula (PTCF). METHODS: Retrospective, interventional case series of consecutive patients diagnosed with PTCF over a 6-year study period between June 2016 and June 2022. The demographics, mode of injury, location, and communication of the canalicular fistula were noted. The outcomes of several management modalities including dacryocystorhinostomy, lacrimal gland therapies, and conservative approaches were assessed. RESULTS: Eleven cases with PTCF over the study period were included. The mean age at presentation was 23.5 years (range: 6-71 years), with male: female ratio of 8:3. The median time interval between trauma to presentation at the Dacryology clinic was 3 years (range: 1 week to 12 years). Seven had iatrogenic trauma and four had the canalicular fistula following primary trauma. Management modalities pursued include conservative approach for minimal symptoms, and dacryocystorhinostomy, dacryocystectomy, and lacrimal gland botulinum toxin injection. The mean follow-up period was 30 months (range: 3-months-6 years). CONCLUSION: PTCF is a complex lacrimal condition and the management of the PTCF needs a tailored approach guided by its nature and location and patient symptomatology.

[Watery eyes: diagnostic and therapeutic considerations]. / Tranende ogen.

Tear complaints can arise from either an increased tear production or from a disturbed tear drainage. Increased tear production from the lacrimal gland is a neuroregulated response to a dried out or irritated ocular surface. Dryness often results from a reduced quality of the tear film, but can also be caused by eyelid malposition with increased globe exposure. Impaired tear drainage usually occurs when the lacrimal drainage system is blocked at the level of the ductus nasolacrimalis, the canaliculi or the lacrimal punctae. Anatomical knowledge of the lacrimal system is necessary to distinguish between the different causes. Using cases and illustrations, we provide insight into the diagnostic considerations for a patient with a watery eye.

Supernumerary lacrimal puncta: case series and review of the literature.

We report a case series of supernumerary puncta-canaliculi, a very rare congenital anomaly, and describe different clinical presentations and new treatment options. This is a retrospective chart review of patients diagnosed with supernumerary lacrimal puncta during the time between June 2015 and December 2021 at the Research Institute of Ophthalmology, Giza, Egypt. Four patients (two females and two males) with a mean presenting age of 54 ± 14 years had unilateral double puncta. Of those four patients, three had double puncta on the right lower eyelid whereas one had double puncta on the left upper and lower eyelid. In one of the three patients, the double puncta anomaly was an incidental finding, and the patient was asymptomatic. The other three patients had associated epiphora. All four patients were found to have patent double puncta with no mechanical obstruction. No surgical interventions were necessary for all four patients as one resolved after discontinuing the topical eye drops. Another patient resolved after the diagnostic probing of the puncta, and the third asymptomatic patient required no interventions. Epiphora in the fourth patient resolved with botulinum toxin injection in the lacrimal gland. Accessory lacrimal puncta can present in patients as an incidental asymptomatic finding or patients may present with epiphora. Patients who present with unilateral epiphora, dry eye, or canaliculitis should be carefully evaluated with a detailed slit-lamp examination using lid eversion to appreciate potentially easily missed supernumerary lacrimal puncta.

Lacrimal Sac Tumors: A Single-institution Experience, Including New Insights.

BACKGROUND/AIM: Lacrimal sac tumors are rare tumor types, with a long time interval from disease onset to diagnosis. We aimed to investigate the characteristics and outcomes of patients with lacrimal sac tumors. PATIENTS AND METHODS: The medical records of 25 patients with lacrimal sac tumors initially treated at the Kyushu university hospital from January 1996 to July 2020 were reviewed. RESULTS: Our analysis included 3 epithelial benign tumors (12.0%) and 22 malignant (88.0%) tumors (squamous cell carcinoma, n=6; adenoid cystic carcinoma, n=2; sebaceous adenocarcinoma, n=2; mucoepidermoid carcinoma, n=1; malignant lymphoma, n=10). The average time from symptom onset to diagnosis was 14.7 months (median=8 months; range=1-96 months). The analysis of patients revealed that lacrimal sac mass (22/25, 88.0%) was the most frequent symptom and a possible tumor marker. Most epithelial benign (n=3) and malignant epithelial (n=12) tumors were treated surgically (14/15, 93.3%). One malignant case was treated with heavy ion beam therapy. Eight patients were treated with postoperative (chemo)radiation therapy because of positive surgical margins (including one unanalyzed case). Local control was ultimately achieved in all but one case. The patient survived for 24 months with immune checkpoint inhibitors and subsequent chemotherapy for local and metastatic recurrence. CONCLUSION: We report our experience in the diagnosis and treatment of lacrimal sac tumors and analyze the clinical trends in cases involving these tumors. Postoperative radiotherapy and pharmacotherapy, including immune checkpoint inhibitors, may be useful for recurrent cases.

Adenoid Cystic Carcinoma from the salivary and lacrimal glands and the breast: Different clinical outcomes to the same tumor.

Adenoid cystic carcinoma (ACC) is a biphasic malignant lesion that can develop at various anatomical sites. Salivary and lacrimal ACC lesions have a high risk of local invasion, metastasis, and poor prognosis. In more distant organs, such as the breast, ACC is a rarer and less aggressive lesion. One of the major predictors of mortality of ACC is perineural invasion, which can be seen in 30 % of breast lesions, 85% of salivary lesions, and almost 100 % of lacrimal gland tumors. The biological differences between these three ACC tumors are still poorly understood. We focused on the current understanding of the genetic variations observed on ACC tumors and prognostic differences associated with distinct anatomical sites. A special effort was made to present the currently available therapies alongside the emerging strategies under development.

[Chinese expert consensus on the diagnosis and treatment of epithelial tumors of the lacrimal gland (2021)].

Orbital tumors frequently occur in the regions where the lacrimal gland is located. Lacrimal gland tumors account for about 10% of orbital space-occupying lesions. Among them, 20% to 50% were epithelial tumors, with benign tumors accounting for 55% and malignant tumors accounting for 45%. Epithelial lacrimal gland tumors usually have a special location with relatively distinctive manifestations, and the treatment principle is different from other orbital space-occupying lesions. Improper treatment often leads to recurrence and even malignant transformation, which compromise the prognosis and life quality of patients. In view of this, the Oculoplastic and Orbital Disease Group of Chinese Ophthalmological Society has put forward the expert consensus on the diagnosis and treatment of epithelial lacrimal gland tumors after serious discussion, in order to improve the level of diagnosis and treatment of this disease in China. (Chin J Ophthalmol, 2021, 57: 658-662).

Microbial Reconstitution Improves Aging-Driven Lacrimal Gland Circadian Dysfunction.

Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. The current study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. The rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle in the old ELG group. Intervention with serial FMT from young donors for 1 month rejuvinated the gut microbial community of the old mice. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the study shows that reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.

Tumor de glándula lacrimal: a propósito de un caso / Lacrimal gland tumor: a case proposal

INTRODUCCIÓN: El carcinoma adenoide quístico (CAQ) es conocido por su lento crecimiento, su tendencia a la recurrencia local y al desarrollo de metástasis a distancia incluso décadas después del diagnóstico inicial, y a pesar de terapias agresivas. OBJETIVO: Presentar el caso de una paciente con CAQ de la glándula lagrimal, tumor muy infrecuente que representa casi el 10% de las lesiones orbitarias ocupantes de espacio. De éstas el 20-30% son de origen epitelial, de las cuales el 55% son lesiones benignas y el 45% malignas. El CAQ es el más común de los tumores epiteliales malignos de la glándula lagrimal (65%). CASO CLÍNICO: Presentamos el caso clínico de una paciente con CAQ de glándula lacrimal diagnosticado de forma incidental tras la realización de TAC desde la consulta de psiquiatría. RESULTADOS Y CONCLUSIONES: El síntoma de presentación más frecuente suele ser la proptosis, acompañada o no de dolor, aunque también puede presentarse como ptosis mecánica, reducción de visión y diplopía. La cirugía radical no ha demostrado mejorar la supervivencia o reducir la recurrencia local en comparación con un abordaje quirúrgico, más conservador en pacientes con tumores de menor tamaño y sin afectación ósea. Las mayores tasas de supervivencia se han conseguido, en pacientes tratados con quimioterapia, con quimioterapia citorreductiva intra-arterial seguida de exenteración orbital y radioterapia.

INTRODUCTION:The adenoid cystic carcinoma (ACC) is known for its slow growth, a tendency to local recurrence and the development of distant metastases even decades after the initial diagnosis, and despite aggressive therapies. AIM:We present the case of a patient with a lacrimal gland tumor. They are very rare tumors that represent almost 10% of space-occupying orbital lesions, of which 20-30% are of epithelial origin, of these, 55% are benign and 45% are malignant. The ACC is the most common malignant epithelial tumor (65%). CASE REPORT :We present the clinical case of a patient with ACC of the lacrimal gland incidentally diagnosed after performing a CT scan from the psychiatric office. RESULTS AND CONCLUSIONS:The most frequent presentation symptom is usually proptosis, accompanied or not accompanied by pain, although it can also occur as mechanical ptosis, vision reduction, and diplopia. Radical surgery has not been shown to improve survival or reduce local recurrence compared to a more conservative surgical approach in patients with smaller tumors and without bone involvement. The highest survival rates have been achieved, in patients treated with chemotherapy, with intra-arterial cytoreductors (IACC) followed by orbital exenteration and radiotherapy.

New strategies for the management of ocular surface disease in glaucoma patients.

PURPOSE OF REVIEW: Glaucoma patients commonly suffer from ocular surface disease (OSD). As treatment strategies, medications and devices for the treatment of OSD as well as glaucoma surgical approaches evolve rapidly, it is important to consider their application to these patients. RECENT FINDINGS: OSD in glaucoma patients may lead to reduced reliability of diagnostic tests, decreased medication compliance, poor surgical outcomes, and overall decreased quality of life. Chronic use of topical glaucoma medications has been linked to the development of limbal stem cell deficiency, and the role of preservatives in OSD continues to be demonstrated. Preservative free glaucoma medications as well as new anti-inflammatory agents for the treatment of OSD are now available. Omega-3 fatty acid supplementation and punctal plugs have been shown to benefit glaucoma patients with OSD. Drop burden may be reduced through the use of the new sustained-release delivery systems, selective laser trabeculoplasty, and minimally invasive glaucoma surgery. SUMMARY: There are multiple emerging strategies for managing OSD that may be applied to patients with glaucoma. With continued research and clinical experiences, we hope to better understand the multifaceted relationship between glaucoma and OSD and develop evidence-based algorithms for the management of these complex patients.

Dacryops with extensive lacrimal and maxillary bone defects in four dogs.

OBJECTIVE: To describe and discuss ventromedial orbital lacrimal gland or duct cysts (dacryops) in dogs with extensive bone defects based on their symptoms, results of diagnostic imaging and histopathological examination, and therapy and discuss their potential origin based on the morphology. ANIMALS STUDIED: Four dogs of different breeds, age, and sex were presented with a unilateral round, slow growing, indolent, and non-tender process ventromedial to the nasal canthus of the eye. PROCEDURES: Transverse computed tomography showed a low-density, non-contrast-enhancing cystic process ventromedial to the globe with extensive defects in the lacrimal and maxillary bones in all cases. The cystic character of the structure was confirmed by the aspiration of the brownish fluid without cellular and microbiological contents. For treatment, the cystic fluid was aspirated, and the sclerosing agent polidocanol was injected in three cases. Cystorhinostomy (nasal marsupialisation) was performed in one case as the first choice and in another case following failure of sclerotherapy. Histopathological examination of the cyst walls was performed in two cases and confirmed the diagnosis of dacryops. RESULTS: Follow-up between 2 and 18 months showed no recurrence and very good to excellent cosmetic results. CONCLUSIONS: Aberrant lacrimal gland or duct tissue with secondary development of dacryops should be included in the differential diagnoses of ventromedial orbital cysts. Large cysts near the lacrimal drainage system with extensive bone defects in dogs should be treated by nasal marsupialization. Treatments such as evacuation of the cyst and inducing sclerosis (sclerotherapy) should be reserved for exceptional cases.

Prognostic factors for local recurrence and survival and impact of local treatments on survival in lacrimal gland carcinoma.

BACKGROUND/AIMS: To identify prognostic factors for local recurrence, distant metastasis and disease-specific survival (DSS) for lacrimal gland carcinoma. METHODS: All consecutive patients with lacrimal gland carcinoma treated from January 1998 through December 2018 were included. Log-rank tests and univariate Cox proportional hazards regression models were used to study risk factors and survival. RESULTS: Overall, 55 patients were included in this study, and 5 patients were excluded from the survival analysis. Median age was 46 years (range: 10-76). 43 patients (78%) had adenoid cystic carcinoma (ACC). 31 patients (56%) had T2 disease at presentation. 28 patients (51%) underwent orbital exenteration with or without adjuvant radiotherapy or chemoradiation, 26 (47%) underwent eye-sparing surgery with or without adjuvant radiotherapy or chemoradiation, and 1 received palliative chemoradiation. 11 patients (22%) experienced local recurrence; 14 (29%) experienced distant metastasis. Five- and 10-year local-recurrence-free survival rates were 0.71 (95% CI 0.58 to 0.88), and 5- and 10-year distant-metastasis-free survival rates were 0.67 (95% CI 0.53 to 0.85) and 0.49 (95% CI 0.30 to 0.81), respectively. There was no significant difference in risks of local recurrence, distant metastasis or DSS between ACC patients who had orbital exenteration and those who had eye-sparing surgery. Perineural invasion was negatively associated with local-recurrence-free survival (p=0.02). Among patients with ACC, basaloid/solid histologic type was associated with significantly worse DSS than non-basaloid/solid histologic type (p<0.01). CONCLUSIONS: For lacrimal gland carcinoma, orbital exenteration with adjuvant therapy and eye-sparing surgery with adjuvant therapy are associated with similar recurrence outcomes. Eye-sparing surgery is associated with better DSS. Perineural invasion is a risk factor for local recurrence. ACC with basaloid/solid subtype correlates with worse DSS.

Residual Epiphora After Successful Periocular Surgery for Facial Paralysis: Pathophysiology and Management.

The prevalence of residual epiphora following successful periocular surgery for facial nerve paralysis can be as high as 30% or more. The pathophysiology of residual epiphora is complex, but identification of the etiology is paramount because the therapeutic approach varies accordingly. Treatments range from medical management of systemic disease to botulinum toxin injections for conditions that arise from aberrant reinnervation to surgical procedures that bypass the lacrimal drainage system completely. We describe a case report and review the pathophysiology and management of residual epiphora to provide a treatment algorithm for clinical use by facial plastic and oculoplastic surgeons. Laryngoscope, 131:E420-E422, 2021.

Primary Malignant Epithelial Tumors of the Lacrimal Drainage System: A Major Review.

Purpose: To perform a literature review on the primary malignant epithelial tumors (PMET) involving the lacrimal drainage system (LDS).Methods: The authors performed a PubMed search of all articles published in English on primary malignant epithelial tumors of the lacrimal sac and the nasolacrimal duct. Data analyzed include prevalence, demographics, clinical presentation, histopathological subtypes, management modalities, outcomes, and recurrence rates.Results: Malignant epithelial tumors of the lacrimal sac are commonly diagnosed in the fifth to seventh decades of life (mean age: 58 years) and have no gender predilection. Typical clinical presentation includes epiphora (84%) and lacrimal fossa mass lesion (78%). Pain (9%) and blood-stained epiphora (4%) were inconsistent findings. Among the PMET, squamous cell carcinomas (SCCs) were the most common (61%) followed by transitional cell carcinomas (TCC; 15%), and mucoepidermoid carcinoma (MEC; 7%). Complete surgical excision followed by radiotherapy (59%) was the preferred modality of management, and only 18% required orbital exenteration. Of the 331 tumors with available treatment details, 85% survived at a mean follow-up of 33 months. The overall recurrence rate following treatment was 20% (65/331). MECs of the lacrimal sac had the best while adenoid cystic carcinoma had the worst prognosis.Conclusion: Blood-stained epiphora was not the classical presentation for primary epithelial malignancies of the LDS. No validated staging system exists for lacrimal drainage tumors. There is a need for consistent and detailed reporting in the literature, more so on the histological subtypes and their management.