Accessory Lacrimal Glands Research Articles

Strategies for Regenerating the Lacrimal Gland.

Aqueous deficient dry eye disease, a significant cause of morbidity worldwide, is due to dysfunction of the main and accessory lacrimal glands. Recent advances in efforts to regenerate lacrimal gland are reviewed. Several strategies are being explored: ex vivo culture models of human and non-human lacrimal gland epithelial and myoepithelial cells, isolation and characterization of adult precursor cells within lacrimal glands, directed differentiation of stem cells to lacrimal gland cells, and organogenesis and engraftment techniques. Conditions for primary cell culture and expansion are being established and will help in the characterization of lacrimal cells. Presumed adult precursor cells have been isolated, laying down foundations for regeneration. Stem cells have been induced to express features of lacrimal gland cells. Engraftment of ex vivo cultured lacrimal tissue is proof of concept that lacrimal gland regeneration and repopulation is possible.

Influence of Ophthalmic Solutions on Tear Components.

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Proteomics of tear fluid

SummaryThe tear film overlying the delicate ocular surface epithelial cells are a complex extra‐cellular fluid with components from the orbital and accessory lacrimal glands, ocular surface epithelial cells, goblet cells, Meibomium glands and as an ultrafiltrate of the blood. Molecular information regarding the health of the ocular surface is reflected in both the quantity and quality of the tear constituents. Moreover, this information can be acquired quantitatively and used for the diagnosis, prognosis and treatment of ocular surface disease and can be used as biomarkers for precision medicine. Recent studies have shown that the tear proteome contains over 1,500 identifiable proteins. Highly abundant proteins include lysozyme, lactoferrin, lipocalin, lacritin, and the proline rich proteins. The tear proteome is clearly shown not to be a simple reflection of the blood. As an extracellular fluid, inflammation is revealed in the tear fluid by upregulation of the pro‐inflammatory proteins S100A8 and S100A9.

Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

ABSTRACTPurpose: The accessory lacrimal glands (ALGs) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential, and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics.Materials and Methods: ALG tissues obtained from Muller’s muscle conjunctival resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers.Results: Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2, and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES.Conclusions: Thus, we report for the first time that human ALG tissues contain precursor marker-positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES, and isolate candidate precursor cells from ALG tissue.

Accessory lacrimal gland duct cyst: 23 years of experience in the Saudi population.

BACKGROUND AND OBJECTIVESAccessory lacrimal gland ductal cyst is a rare clinical entity that has been reported after trauma, infection, or conjunctival inflammation. Trachoma has been postulated as an etiologic factor for this dacryops in Saudis. We studied the prevalence, demographics, clinicopathological features and surgical approach for these lesions.DESIGN AND SETTINGRetrospective study of 23 consecutive ductal cysts diagnosed clinically and proved histopathologically at King Khaled Eye Specialist Hospital (KKESH) over 23 years (1991–2014).PATIENTS AND METHODSData on patient demographics, clinical features, surgery, and outcome were collected by chart review. The histopathologic slides were reviewed by a single pathologist.RESULTSOf 23 cases of accessory lacrimal gland ductal cysts confirmed histopathologically, 14 were males and 9 females with a median age of 38.8 years. Cysts were located in the upper eyelid in 73.9%. The commonest presentation was a painless eyelid mass in 91.3%. Excision by conjunctival incision was performed in 14 and intra-operative perforation occurred in 9. Trachomatous scarring was evident in 39.1% but did not have significance in relation to this rupture. No recurrences have been observed with a mean follow up of 34.6 months.CONCLUSIONThe approximate prevalence of accessory lacrimal gland dacryops in the Saudi population is 1/6800. Trachoma does not seem to be a major predisposing factor. They are more frequent in males. Their histopathological appearance is identical regardless of origin. The presence of conjunctival scarring, dacryops size, and the surgical incision type did not seem to have significant correlation with the iatrogenic rupture of the cyst. We recommend careful dissection for complete cyst excision through conjunctival approach with no expected recurrence.

Un kyste lacrimal atypique

Lacrimal cysts are rarely described and must be differentiated from diseases of the lacrimal gland. We present a rare case of lacrimal cyst developed from an accessory lacrimal gland. The management consisted of excision using a tarsoconjonctivale approach. Most cysts are diagnosed from the third decade, manifested by progressive exophthalmos. It is a benign disease. However, the differential diagnosis with malignancy is not excluded. Surgical resection is desirable if tumors become symptomatic.

Computed tomographic imaging characteristics of the normal canine lacrimal glands.

BackgroundThe canine lacrimal gland (LG) and accessory lacrimal gland of the third eyelid (TEG) are responsible for production of the aqueous portion of the precorneal tear film. Immune-mediated, toxic, neoplastic, or infectious processes can affect the glands directly or can involve adjacent tissues, with secondary gland involvement. Disease affecting these glands can cause keratoconjunctivitis sicca, corneal ulcers, and loss of vision. Due to their location in the orbit, these small structures are difficult to evaluate and measure, making cross-sectional imaging an important diagnostic tool. The detailed cross-sectional imaging appearance of the LG and TEG in dogs using computed tomography (CT) has not been reported to date.ResultsForty-two dogs were imaged, and the length, width, and height were measured and the volume calculated for the LGs & TEGs. The glands were best visualized in contrast-enhanced CT images. The mean volume of the LG was 0.14 cm3 and the TEG was 0.1 cm3. The mean height, width, and length of the LG were, 9.36 mm, 4.29 mm, and 9.35 mm, respectively; the corresponding values for the TEG was 2.02 mm, 9.34 mm, and 7.90 mm. LG and TEG volume were positively correlated with body weight (p < 0.05).ConclusionsContrast-enhanced CT is a valuable tool for noninvasive assessment of canine lacrimal glands.

Effect of Subconjunctival Lacrimal Gland Transplantation in a Rabbit Dry Eye Model

The main and accessory lacrimal glands are involved in reflex and basal secretion of tears, respectively, with the glandular tissue anatomy being similar for both glands. We transplanted part of the main lacrimal gland under the palpebral conjunctiva in a rabbit dry eye model and assessed the therapeutic effect of this procedure. In New Zealand White rabbits, the greater superficial petrosal nerve was cut unilaterally under a microscope. The other eye served as a normal control. For transplantation, approximately 0.07 g of the main lacrimal gland was harvested from the normal side, labeled with octadecylindocarbocyanine, and transplanted under the palpebral conjunctivae of both eyes. At 1 week and 1 month after the transplantation, the eyes were observed, and the Schirmer tear test and histological examination of the palpebral conjunctiva were performed. On the denervated side, tear flow, measured by the Schirmer tear test, recovered at 1 month after the transplantation of the main lacrimal gland compared with that before transplantation. The contralateral control side showed no changes. On the denervated side, the fluorescein score significantly improved at 1 month after transplantation compared with that before transplantation (P < 0.005), whereas the rose bengal score showed no difference. Histological examination revealed that octadecylindocarbocyanine-labeled transplanted main lacrimal gland tissue was present under the palpebral conjunctiva. These results suggest that the partial transplantation of the main lacrimal gland may be effective for treatment of dry eyes.

Ocular manifestations of graft-versus-host disease

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT.Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production.Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva.Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation.

Anatomy of Secretory Glands in the Eyelid and Conjunctiva

The eyelid and conjunctiva are main targets in ophthalmic plastic surgery. Although dry eyes are known to occasionally occur after ophthalmic plastic surgery, little attention has been paid to the secretory glands in the eyelid and conjunctiva. The secretary glands in the eyelid and conjunctiva contain the main lacrimal gland, accessory lacrimal glands of Wolfring and Krause, goblet cells, ciliary glands of Moll and Zeis, and the meibomian gland of the tarsal plate. Understanding the details of these glands is helpful in preventing and managing secretion reduction after oculoplastic procedures.

A Rare Case Report of Cyst of Wolfring

Ductal cysts of the accessory lacrimal glands of Wolfring and Krause are uncommon and are rarely reported in the ophthalmic literature. We report a rare case of cyst arising from accessory lacrimal gland of Wolfring in a young male boy. A 17 year old male patient came with painless bulging mass under conjunctiva of lower fornix near medial canthus of right eye. It was gradually increasing since one year. Magnetic resonance Imaging (MRI) scan revealed 20x20x14 mm well defined smooth walled cyst. Cyst was removed under general anaesthesia through conjunctival route. Histopathological examination was consistent with cyst arising from accessory lacrimal gland of Wolfring.

Pleomorphic Adenomas of the Lower Eyelid

Pleomorphic adenomas are well-recognized tumors usually arising within the main lacrimal gland. Their occurrence, however, is not limited to the main lacrimal gland. There have been cases reported in the eyebrow, upper eyelid, lateral lower eyelid, lacrimal sac, and even intraocularly. The medial aspect of the lower eyelid is a very rare site of occurrence because it is largely devoid of accessory lacrimal glands. We describe 2 cases of pleomorphic adenomas arising in the medial aspect and 1 case arising in the middle of the lower eyelid, respectively. The likely origin of these tumors at this location is from ectopic lacrimal gland.

PERIOCULAR ANTERIOR ADNEXAL ANATOMY AND CLINICAL ADNEXAL EXAMINATION OF THE ADULT ASIAN ELEPHANT (ELEPHAS MAXIMUS)

Formalin preserved ocular-associated anterior adnexa tissues from five necropsied Asian elephants (Elephas maximus) were dissected with attention to the palpebrae, conjunctiva, nictitating membranes, nasolacrimal ducts, and periocular glandular tissues. Gross and histologic examination revealed that lacrimal and tarsal glands were not present. Evidence of the lacrimal drainage apparatus, including lacrimal punctae or any remnant of lacrimal sacs, was also absent. In contrast, well-developed sebaceous glands associated with accessory hairs along the palpebrae were exceptionally abundant. Mixed-secreting accessory lacrimal glands were noted in the deep stroma posterior to the tarsus of both palpebrae and the gland of the nictitating membrane. Apparently, the Asian elephant has developed a novel tear system in the absence of lacrimal and tarsal (meibomian) glands. Clinical examinations and bacterial cultures of the visible periocular tissues were performed on eight living adult Asian elephants to confirm the postmortem anatomic findings and provide guidance to the clinician during examination of the elephant conjunctiva.

Gene Expression in Human Accessory Lacrimal Glands of Wolfring

The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. Of the 24 most highly expressed genes, 9 were of direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to protein synthesis, targeting, and secretion, and a large number of genes for proteins with antimicrobial activity were detected. Ion channels and transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes for control of lacrimal function, including cholinergic, adrenergic, vasoactive intestinal polypeptide, purinergic, androgen, and prolactin receptors were also expressed in gland of Wolfring. The data suggest that the function of glands of Wolfring is similar to that of main lacrimal glands and are consistent with secretion electrolytes, fluid, and protein under nervous and hormonal control. Since these glands secrete directly onto the ocular surface, their location may allow rapid response to exogenous stimuli and makes them readily accessible to topical drugs.

Oncocytic lesions of the ophthalmic region: a clinicopathological study with emphasis on cytokeratin expression

This study aimed to make a nationwide clinicopathological study of oncocytic lesions in the ophthalmic region and to characterize their cytokeratin (CK) expression. All histologically diagnosed oncocytic lesions in the ophthalmic region registered in Denmark over a 25-year period were collected and re-evaluated using a monoclonal antimitochondrial antibody (MU213-UC). Clinical data were registered. Immunohistochemical characterization was performed with a panel of anti-CK antibodies. A total of 34 oncocytic lesions were identified and reviewed. The incidence that required surgical intervention in the Danish population could be approximated to 0.3 lesions per million capita per year. Patient ages ranged from 45 years to 89 years, with a peak incidence in the eighth decade. Female patients were twice as common as male. Lesions were typically described as red–brown, cystic and slow-growing. The antimitochondrial antibody MU213-UC produced a distinct and intense immunostaining of all oncocytic lesions and was found to be useful in substantiating oncocytic differentiation. Twenty-six of the lesions originated in the caruncle, three in the conjunctiva, two in the lacrimal sac, one at the semilunar plica, one on the eyelid margin and one peripunctally. Lesions were histologically classified as adenoma (oncocytoma) (26), hyperplasia (4) and metaplasia (4). Fourteen oncocytic lesions representing different locations and differentiation were further evaluated for CK expression. Basal-type oncocytic cells reacted with antibodies against CK 5 ⁄ 6, CK 7, CK 8, CK 13, CK 14, CK 17, CK 18 and CK 19, and suprabasal cells with CK 4, CK 7, CK 8, CK 18 and CK 19. Antibodies against CK 1+10 and CK 20 showed no reaction. Oncocytic lesions of the ophthalmic region most frequently present as caruncular oncocytomas. The CK profile is similar to the lacrimal- and accessory lacrimal gland duct elements and supports the theory that these lesions originate in the lacrimal- and accessory lacrimal glands.

Das Fasanella-Servat-Verfahren zur Therapie der erworbenen Ptosis

The oculoplastic surgeon may choose between several surgical procedures to treat ptosis of the eyelid. One such potential therapeutic option is the Fasanella-Servat procedure. The purpose of our study was to evaluate the postoperative outcome of the Fasanella-Servat procedure in patients with ptosis of the eyelid with regard to objective and subjective criteria. The postoperative success of 20 patients (23 eyelids), 11 female and 9 male, with acquired ptosis of the upper eyelid who underwent the Fasanella-Servat procedure between 1995 and 2004 in an eye tertiary care centre, was evaluated. With regard to the type of ptosis, the pre- and postoperative opening of the eyelid, the levator function, and the symmetry between both eyes were analysed statistically. The patients' subjective satisfaction with the functional and cosmetic postoperative outcome was evaluated by means of a nominal questionnaire (scale 1 - 5). The intraoperatively removed tissue was analysed histopathologically for accessory lacrimal glands or levator muscle. The mean preoperative opening of the eyelid was 7.1 mm (min. 4 mm, max. 10 mm) with a mean levator function of 12.6 mm. Postoperatively, the opening of the eyelid improved significantly to 9.3 mm (min. 7 mm; max. 14 mm), while the levator function remained stable. The preoperative asymmetry between both eyes was significantly decreased. 90 % of the patients were satisfied with the cosmetic and functional results. There were no early and late postoperative complications. No side effects were recorded following treatment. The intraoperatively removed tissue showed no evidence of tissue of accessory lacrimal gland or levator muscle. The Fasanella-Servat procedure remains an effective procedure in treating mild ptosis with few complications and good cosmetic and functional results.

Pathophysiology of dry eye syndrome

AbstractDry eye or dysfunctional tear syndrome is a highly prevalent disease worldwide. It is related to a pathological condition of anyone of the parts of the “ocular surface system” that involves the cornea, conjunctiva, lacrimal gland, accessory lacrimal glands, nasolacrimal duct and the lids with the meibomian glands. These are linked as a functional system by innervation, the endocrine and immune system. Endogenous or exogenous caused alterations in one or several components of the ocular surface system or its secretions result in changes of the tear film or ocular surface provoking inflammation. With time, inflammatory reactions may lead to corneal neuropathy compromising the reflex response of the lacrimal glands. Additionally a self‐perpetuating vicious circle with loss of function and damage can be initiated also by an immune‐modulated inflammation.

Surgical Microanatomy of the Müller Muscle-Conjunctival Resection Ptosis Procedure

To assess for alterations in the microscopic anatomy that occur as a result of the Müller muscle-conjunctival resection (MMCR) ptosis procedure and to better understand the mechanisms by which MMCR elevates the eyelid. Sixteen orbits from 8 fresh frozen Caucasian cadaver heads, ranging from 38 to 100 years of age were used. For each head, MMCR was performed on one side. The contralateral, unoperated orbit served as an anatomic control. Each exenterated orbital contents and excised MMCR specimen was evaluated. The histopathology of the eyelids and MMCR specimens were studied microscopically by staining with hematoxylin-eosin, elastic, and Verhoeff-Masson trichrome. Müller muscle and conjunctiva were present in all 8 of the excised MMCR specimens. Elastic fibers consistent with Müller muscle tendon or among the smooth muscle fibers were seen within all excised MMCR specimens. The levator aponeurosis was intact in 8 of 8 operated eyelids; however, the aponeurosis was plicated in all. The accessory lacrimal gland tissues were intact in all of the operated and unoperated eyelids. MMCR works by shortening the posterior lamella, which results in advancement of the levator palpebrae superioris muscle and plication of the levator aponeurosis. Plication of the levator aponeurosis likely contributes to the increased volumetric effect seen clinically after MMCR. Phenylephrine testing can help in fine-tuning the amount of resection, but given the mechanism of action of MMCR, adequate levator muscle function remains a critical factor in the success of the surgery. Moreover, MMCR preserves accessory lacrimal gland tissues.

Oncocytic lesions of the ophthalmic region

Abstract Purpose To make a nationwide clinicopathologic study of oncocytic lesions in the ophthalmic region and to characterize their cytokeratin(CK) expression. Methods All histologically diagnosed oncocytic lesions in the ophthalmic region registered in Denmark over a 25‐year period were collected and re‐evaluated using a monoclonal antimitochondrial antibody (MU213‐UC). Clinical data were registered. Immunohistochemical characterization was performed with a panel of anticytokeratin antibodies. Results A total of 34 oncocytic lesions were identified. The incidence that required surgical intervention in the Danish population could be approximated to 0.3 lesions per million capita per year. The age of the patients ranged from 45 to 89 years with a peak incidence in the 8th decade. Female gender was twice as common as male. Lesions were typically described as red‐brown, cystic and slow growing. The antimitochondrial antibody MU213‐UC produced a distinct and intense immunostaining. 26 of the lesions originated from the caruncle, three in the conjunctiva, two in the lacrimal sac, one at the semilunar plica, one on the eyelid margin and one peripunctal. Lesions were histologically classified as adenoma(oncocytoma) (26), hyperplasia (4) and metaplasia (4). Basal‐type oncocytic cells reacted with antibodies against CK5/6, CK7, CK8, CK13, CK14, CK 17, CK18, CK19 and suprabasal cells with CK4, CK7, CK8, CK18 and CK19. Antibodies against CK1+10 and CK20 showed no reaction. Conclusion Oncocytic lesions of the ophthalmic region most frequently present as a caruncular oncocytoma. The cytokeratin profile is similar to the lacrimal ‐ and accessory lacrimal gland duct elements and supports the theory that these lesions originate from lacrimal – and accessory lacrimal glands.

Histopathological study of lesions of the caruncle: a 15-year single center review

IntroductionThe caruncle is a modified cutaneous tissue located at the inner canthus that contains hair follicles, accessory lacrimal glands, sweat glands and sebaceous glands. These different types of tissues can give rise to a wide variety of lesions that make the clinical diagnosis difficult. The aim of the study was to investigate the most common types of caruncle lesions and the clinical and pathological correlation.MethodsRetrospective, observational case series. Records of caruncle lesions examined at the Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Canada, between 1993 and 2008 were analyzed, comparing the clinical and histopathological findings.ResultsA total of 42 lesions from 42 patients were analyzed. Twenty-six (61.90%) of the patients were women and 16 (38.10%) were men and the age range from 20 to 84. The main diagnoses were: 16 epithelial lesions (38.09%), 14 inflammatory lesions (31.70%), 10 melanocytic lesions (21,95%), 2 lymphoid lesions (4.87%). From the 28 cases that had a preoperative clinical hypothesis only 17 presented a histopathological confirmation of the diagnosis (60.71%).ConclusionThe most common caruncle lesions were epithelial tumors followed by chronic inflammation and melanocytic lesions. Although most of the lesions were benign, there was a great number of misdiagnose based on the clinical suspicious.