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Current Opinion in Ophthalmology Jul 2021Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited... (Review)
Review
PURPOSE OF REVIEW
Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED.
RECENT FINDINGS
Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types.
SUMMARY
Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.
Topics: Complementary Therapies; Dry Eye Syndromes; Humans; Lacrimal Apparatus
PubMed: 34010229
DOI: 10.1097/ICU.0000000000000768 -
Cell Stem Cell Jul 2021The lacrimal gland is essential for lubrication and protection of the eye. Disruption of lacrimal fluid production, composition, or release results in dry eye, causing...
The lacrimal gland is essential for lubrication and protection of the eye. Disruption of lacrimal fluid production, composition, or release results in dry eye, causing discomfort and damage to the ocular surface. Here, we describe the establishment of long-term 3D organoid culture conditions for mouse and human lacrimal gland. Organoids can be expanded over multiple months and recapitulate morphological and transcriptional features of lacrimal ducts. CRISPR-Cas9-mediated genome editing reveals the master regulator for eye development Pax6 to be required for differentiation of adult lacrimal gland cells. We address cellular heterogeneity of the lacrimal gland by providing a single-cell atlas of human lacrimal gland tissue and organoids. Finally, human lacrimal gland organoids phenocopy the process of tear secretion in response to neurotransmitters and can engraft and produce mature tear products upon orthotopic transplantation in mouse. Together, this study provides an experimental platform to study the (patho-)physiology of the lacrimal gland.
Topics: Animals; Dry Eye Syndromes; Humans; Lacrimal Apparatus; Mice; Organoids; Stem Cells; Tears
PubMed: 33730555
DOI: 10.1016/j.stem.2021.02.024 -
Arquivos Brasileiros de Oftalmologia 2021The purpose of this article was to report a case of intraconal lacrimal gland tissue and to review the literature on lacrimal gland choristoma. The magnetic resonance... (Review)
Review
The purpose of this article was to report a case of intraconal lacrimal gland tissue and to review the literature on lacrimal gland choristoma. The magnetic resonance imaging findings of a biopsy-proven orbital case are also presented. A PubMed database search was performed using the key terms heterotopic, ectopic, aberrant, choristoma, and lacrimal gland to identify all the previously documented studies on lacrimal gland choristoma, in English, Spanish, and French. We classified the lacrimal gland choristoma cases classified according to the location of the lesions, clinical appearance, management, and outcome. The search targeting the period between 1887 and 2019 returned 79 articles, which were reviewed. We found a total of 113 cases of choristomas with normal lacrimal gland tissue. Only two of them were not associated with the eye or its adnexa while the remaining 111 lesions were found either on the ocular surface (n=46) or in the orbit (n=34). Intraocular choristomas were found in 18 patients, and the rest of the lesions were noted either on the eyelids (n=10) or in the lacrimal drainage system (n=3). Orbital and intraocular choristomas are the most harmful lesions as orbital choristomas are frequently associated with permanent diplopia while intraocular lacrimal gland choristomas have a poor visual prognosis and are a common cause of enucleation of the eye. In one of the reported cases, a corneal lacrimal gland choristoma had been experimentally induced by activating the FGF10 signaling pathway. Lacrimal gland choristomas are not uncommon. This peculiar type of lesion has been experimentally induced and may appear in a variety of locations associated with the globe and its adnexa.
Topics: Choristoma; Cornea; Humans; Lacrimal Apparatus; Orbit
PubMed: 35416898
DOI: 10.5935/0004-2749.20220029 -
Investigative Ophthalmology & Visual... Mar 2022To investigate microenvironment changes of the lacrimal gland after obstruction of lacrimal gland ducts.
PURPOSE
To investigate microenvironment changes of the lacrimal gland after obstruction of lacrimal gland ducts.
METHODS
The ducts of rat exorbital lacrimal gland were ligated by sutures for different durations. After that, the sutures in some animals were released, and they were observed for 21 days to evaluate the recovery of the lacrimal gland. Slit lamp and tear secretion test was performed to evaluate ocular surface and lacrimal gland function. The lacrimal gland and cornea were harvested and processed for hematoxylin and eosin staining, oil red O staining, LipidTOX staining, Masson staining, quantitative real time polymerase chain reaction, and immunofluorescence staining.
RESULTS
After the lacrimal gland ducts were blocked, tear secretion and the weight of the lacrimal gland were reduced. Incidence of corneal neovascularization increased after seven days. Intraglandular ducts dilated and acini destroyed. Long-term ligation induced fibrosis and lipid accumulation of the lacrimal glands. Inflammatory cell infiltrated and inflammatory factors upregulated. Proliferative and apoptotic cells increased. Structure of myoepithelial cells and basement membrane was destroyed. The p63 expression increased whereas Pax6 expression decreased. After suture release, tear secretion and structure of acini could recover in less than seven days after ligation, with a decrease in inflammatory cell infiltration and fibrosis relief. Apoptotic cells and proliferative cells increased at five days thereafter. The structure of the myoepithelial cells and basement membrane could not recover three days after ligation, and the number of mesenchymal cells increased in ligation after five to 14 days.
CONCLUSIONS
Blockage of the lacrimal gland ducts results in dystrophy of lacrimal gland acini cells, inflammation, and lipid accumulation of the lacrimal gland microenvironment. Long-term duct blockage will cause irreversible lacrimal gland failure.
Topics: Animals; Cornea; Fibrosis; Inflammation; Lacrimal Apparatus; Lipids; Rats
PubMed: 35289845
DOI: 10.1167/iovs.63.3.14 -
Journal of Veterinary Diagnostic... Jan 2022A 9-y-5-mo-old, spayed female, mixed-breed dog with buphthalmia and elevated intraocular pressure in the left eye, consistent with glaucoma, was evaluated....
A 9-y-5-mo-old, spayed female, mixed-breed dog with buphthalmia and elevated intraocular pressure in the left eye, consistent with glaucoma, was evaluated. Black-pigmented, slightly elevated tissue with irregular margins was noted on the dorsolateral aspect of the left globe. Ultrasonography detected a mass, later identified as lacrimal gland, adjacent to the globe and the thickened uvea. The surgically removed lacrimal gland was effaced by dense sheets of melanin-laden cells. Within the enucleated globe, numerous melanin-laden cells infiltrated and expanded the rostral two-thirds thickness of the cornea, the entire anterior uvea (iris and ciliary body), and a rostral portion of the choroid. Melanin-laden cells in the left lacrimal gland and globe showed no nuclear atypia or mitotic figures, and reacted to anti-S100 and anti-melan A antibodies by immunohistochemistry. Our final diagnosis was concurrent lacrimal gland melanocytoma and ocular melanocytosis. The trabecular meshwork of the eye was obliterated by melanin-laden cells, which was the likely cause of glaucoma in this patient. To our knowledge, melanocytoma affecting the lacrimal gland has not been reported previously in a non-human mammalian species. Veterinary clinicians are encouraged to include melanocytoma in the differential list when examining an enlarged lacrimal gland.
Topics: Animals; Dogs; Female; Immunohistochemistry; Lacrimal Apparatus
PubMed: 34515584
DOI: 10.1177/10406387211045027 -
Eye (London, England) Nov 2022Patients with bilateral lacrimal gland disease are a unique subset of patients where there is a paucity of literature. This presentation often represents systemic...
BACKGROUND
Patients with bilateral lacrimal gland disease are a unique subset of patients where there is a paucity of literature. This presentation often represents systemic disease or malignancy and can cause diagnostic difficulties. We aim to describe the diagnoses and features of bilateral lacrimal gland disease.
METHOD
Retrospective multi-centre case series involving 115 patients with bilateral lacrimal gland disease from 1995 to 2020.
RESULTS
115 patients were included. Their ages ranged from 9 to 85 (mean 47.3 years) with a female predominance (73, 63.5%). The most common category of diagnosis was inflammatory (69, 60%) followed by lymphoproliferative (23, 20%), structural (17, 14.8%) and other conditions (6, 5.2%). The five most common specific diagnoses were IgG4 related disease (20, 17.4%) and idiopathic orbital inflammatory disease (20, 17.4%), lymphoma (16, 13.9%), lacrimal gland prolapse (13, 11.3%), and sarcoidosis (11, 9.6%). Corticosteroid treatment was used most commonly (29, 25.2%) followed by observation (25, 21.7%). At last follow up, the majority of patients had complete resolution, significant improvement with mild residual disease or stable disease without further progression (104, 90.4%).
CONCLUSION
Bilateral lacrimal disease may be due to a range of aetiologies, most of which are systemic. The most common are inflammatory and lymphoproliferative conditions. Due to the wide range of aetiologies of bilateral lacrimal gland disease, it is extremely difficult to accurately determine a cause based on clinical findings alone, highlighting the vital role of lacrimal gland biopsy in patients presenting with bilateral lacrimal gland disease.
Topics: Humans; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Sarcoidosis; Retrospective Studies; Biopsy
PubMed: 34725471
DOI: 10.1038/s41433-021-01819-0 -
Normal and Sjogren's syndrome models of the murine lacrimal gland studied at single-cell resolution.Proceedings of the National Academy of... Oct 2023The lacrimal gland is of central interest in ophthalmology both as the source of the aqueous component of tear fluid and as the site of autoimmune pathology in the...
The lacrimal gland is of central interest in ophthalmology both as the source of the aqueous component of tear fluid and as the site of autoimmune pathology in the context of Sjogren's syndrome (SjS). To provide a foundational description of mouse lacrimal gland cell types and their patterns of gene expression, we have analyzed single-cell transcriptomes from wild-type (Balb/c) mice and from two genetically based SjS models, and (nonobese diabetic), and defined the localization of multiple cell-type-specific protein and mRNA markers. This analysis has uncovered a previously undescribed cell type, Car6+ cells, which are located at the junction of the acini and the connecting ducts. More than a dozen secreted polypeptides that are likely to be components of tear fluid are expressed by acinar cells and show pronounced sex differences in expression. Additional examples of gene expression heterogeneity within a single cell type were identified, including a gradient of Claudin4 along the length of the ductal system and cell-to-cell heterogeneity in transcription factor expression within acinar and myoepithelial cells. The patterns of expression of channels, transporters, and pumps in acinar, Car6+, and ductal cells make strong predictions regarding the mechanisms of water and electrolyte secretion. In and lacrimal glands, distinctive changes in parenchymal gene expression and in immune cell subsets reveal widespread interferon responses, a T cell-dominated infiltrate in the model, and a mixed B cell and T cell infiltrate in the model.
Topics: Female; Mice; Male; Animals; Sjogren's Syndrome; Lacrimal Apparatus; Mice, Inbred MRL lpr; Mice, Inbred NOD; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37812717
DOI: 10.1073/pnas.2311983120 -
Indian Journal of Ophthalmology Apr 2023Lacrimal and meibomian glands contribute to the aqueous and lipid components of tear film, respectively. Their evaluation remains central to diagnosing and managing dry... (Review)
Review
Lacrimal and meibomian glands contribute to the aqueous and lipid components of tear film, respectively. Their evaluation remains central to diagnosing and managing dry eye disease (DED). The review discusses the differences and reliability of various diagnostic tests and commercially available devices used for DED diagnosis. Slit-lamp-based techniques are direct palpebral lobe and tear flow assessment, Schirmer test, meibum quality and expressibility, and evaluation of tear meniscus height. Non-invasive tear meniscus height (TMH), tear break-up time (TBUT), lipid layer thickness (LLT), and meibography are machine-based diagnostic tests. The structure-function correlation of the tear-producing glands gives more comprehensive details than either information alone. Many devices are available in the market, which make DED diagnosis an easy feat, but the tests should be interpreted keeping in mind the intra-observer and inter-observer repeatability. Also, the tear film displays a huge variability as per the environmental conditions and impact of blinking. Hence, the examiner should be well versed with the techniques and repeat the test two to three times to obtain an average reading, which is more reliable. The recommended sequence of tests for diagnosing DED is a dry eye questionnaire, TMH, LLT, NIBUT (FBUT if non-invasive test is unavailable but should be performed after osmolarity), tear osmolarity, meibography, and ocular surface staining. Invasive tests such as Schirmer should be performed after the non-invasive tear film diagnostic testing.
Topics: Humans; Meibomian Glands; Reproducibility of Results; Lacrimal Apparatus; Tears; Dry Eye Syndromes; Lipids
PubMed: 37026239
DOI: 10.4103/IJO.IJO_2622_22 -
Asia-Pacific Journal of Ophthalmology... 2017Lacrimal gland tumors are rare and constitute a wide spectrum of different entities ranging from benign epithelial and lymphoid lesions to high-grade carcinomas,... (Review)
Review
Lacrimal gland tumors are rare and constitute a wide spectrum of different entities ranging from benign epithelial and lymphoid lesions to high-grade carcinomas, lymphomas, and sarcomas with large differences in prognosis and clinical management. The symptoms and findings of a lacrimal gland lesion are a growing mass at the site of the lacrimal gland, including displacement of the eyeball, decreased motility, diplopia, and ptosis. Pain is the cardinal symptom of an adenoid cystic carcinoma. Radiological findings characteristically include an oval, well-demarcated mass for benign lesions whereas malignant lesions typically display calcifications, destruction of bone, and invasion of adjacent structures. The diagnosis ultimately relies on histology, as does the choice of treatment and the prognosis. In recent years, the understanding of the biology of numerous types of lacrimal gland neoplasia has improved and the choice of treatment has changed accordingly and holds further promise for future targeted therapies. Treatment of benign epithelial lesions is surgical excision whereas carcinomas often require adjuvant radiotherapy and/or chemotherapy. In contrast, the cornerstone in management of lymphoid lesions is chemotherapy, often including a monoclonal antibody. This article presents an update on the clinical, radiological, histological, and molecular features, along with treatment strategies for tumors of the lacrimal gland.
Topics: Combined Modality Therapy; Eye Neoplasms; Humans; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Prognosis
PubMed: 28399336
DOI: 10.22608/APO.201707 -
Best Practice & Research. Clinical... Mar 2023This paper addresses how to perform an ultrasound assessment of the salivary and lacrimal glands, how to identify pathological changes, and how to score disease... (Review)
Review
This paper addresses how to perform an ultrasound assessment of the salivary and lacrimal glands, how to identify pathological changes, and how to score disease activity, focusing on the use for primary Sjögren's syndrome (pSS). It addresses the role of salivary gland ultrasound for diagnosing and management of patients with pSS and touches upon the use for differential diagnosis, including how and when to perform ultrasound-guided biopsies and injections.
Topics: Humans; Sjogren's Syndrome; Lacrimal Apparatus; Salivary Glands; Ultrasonography; Diagnosis, Differential
PubMed: 37258318
DOI: 10.1016/j.berh.2023.101837