Search

Ocular surface homeostasis plays a vital role in maintaining of eye health. Dry eye disease is one of the prominent and typical manifestations of disruption of ocular surface homeostasis that leads to the worsening of ocular surface homeostasis that leads to the worsening of ocular surface disease when it interacts with other pathogenic factors. However, disruption in ocular surface homeostasis in children is often overlooked because of the current methods of assessing ocular surface homeostasis. This review summarizes the main factors affecting ocular surface homeostasis in children, with the aim of drawing the attention of clinicians to the disruption of ocular surface homeostasis in children when dealing with such diseases. Ocular surface homeostasis involves several interrelated components, each of which plays a nonnegligible role in ocular surface homeostasis. Unlike adults, children have a stronger lacrimal gland secretion capacity and milder symptoms when there is a slight disruption of the ocular surface homeostasis. In addition, children's expressive abilities were weaker. Therefore, dry eye in children is often ignored by doctors and parents, and clinicians should pay more attention to the protection of ocular surface homeostasis when treating children with these diseases. Therefore, there is a need for diagnostic criteria for dry eye disease specific to children., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

HELIX syndrome, characterized by hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia due to claudin-10 (CLDN10) mutations, was recognized in 2017. Here we describe two unrelated Saudi families with this syndrome due to a novel CLDN10 mutation with a unique mechanism of CLDN10 inactivation. The two consanguineous families include 12 affected individuals (three siblings in family 1 and nine members in family 2). They presented with hypokalemia and the above-mentioned features of HELIX syndrome. The underlying mutation was detected by whole exome sequencing, confirmed by Sanger sequencing and functionally indicated by RT-PCR, electrophysiological studies and immunohistochemical staining of transfected HEK293 and MDCK C7 cells, and skin and kidney biopsy tissues. A novel biallelic single nucleotide deletion was identified in exon 5 of CLDN10 (NM_182848.3: c.647delC, p.P216Lfs∗19 for CLDN10a or NM_006984.4: c.653delC, p.P218Lfs∗21 for CLDN10b). The mutation led to frameshift and extension of the original termination codon by nine amino acids with loss of the C-terminus pdz-binding motif. Functional studies showed mRNA degradation and protein retention in intracellular compartments and that the pdz-binding motif is crucial for proper localization of claudin-10 in tight junctions. In the kidney, claudin-10 was replaced by translocation of claudin-2 (proximal tubule) and claudin-19 (thick ascending limb), and in the sweat gland by claudin-3 and occludin. However, these claudins did not functionally compensate for loss of claudin-10. Thus, this novel CLDN10 mutation identified in these two families disrupted the C-terminus pdz-binding motif of claudin-10 causing HELIX syndrome., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the long-term outcomes of surgical occlusion of lacrimal puncta using thermal cautery in the management of ocular surface diseases., Methods: We reviewed medical records of 80 consecutive patients from a single academic center who underwent punctal cauterization. Patient demographics, ocular history, symptoms, and signs of ocular surface diseases pre- and post-cauterization were recorded., Results: A total of 80 patients (171 puncta) were included, with an average age of 59 years and a follow-up duration of 27 months. The most common ocular morbidity was ocular graft-versus-host disease (n = 36), followed by primary keratoconjunctivitis sicca (n = 15). Indications for punctal cauterization included plug loss (n = 51), difficulty in plug fitting (n = 11), plug-related complications (n = 6), recanalization of previous cauterization (n = 7), and severe ocular surface disease requiring permanent punctal closure (n = 4). After punctal cauterization, the percentage of eyes with severe (21%) and moderate (25%) dry eye decreased significantly (8% and 19% at 3 months and 6% and 17% at 12 months, P = 0.0006). Fifty-four percent of patients reported improvement in their symptoms. The rate of recanalization was 21% during the follow-up period. The use of topical corticosteroids was associated with higher recanalization rate. Associated complications were limited to temporary pain and swelling., Conclusions: Punctal cauterization is an effective modality in treating severe ocular surface diseases in patients who repeatedly lose punctal plugs, and it can be easily performed in a clinic setting without major complications. However, cauterization may need to be repeated in up to a quarter of cases because of recanalization., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally ( n = 15, 25 eyes) or transcutaneously ( n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer's I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.

Purpose: Obstruction of the tear drainage causes a range of ocular surface disorders. Hitherto, the genetics of tear duct development and obstruction has been scarcely explored, and related animal models are lacking. This study aims to study the potential role of the Wnt/PCP pathway mediated by Prickle 1 in tear duct development and diseases., Methods: A severe hypomorphic Prickle 1 mutant was generated. Histology and immunohistochemistry were performed to compare wild type, Prickle 1 hypomorphic, and null mutant tear ducts. In situ hybridization was conducted to identify the signaling components in the developing tear ducts. Three-dimensional (3D) reconstruction was used to detect the human embryonic tear duct., Results: Here, we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to the blockage of the tear drainage by incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (LC), which also causes precocious eyelid opening. We observed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. An investigation of the expression of Wnt/PCP core genes demonstrated a subset of PCP signaling components expressed in the developing tear duct. Furthermore, Prickle 1 is not required for the expression of Fgfr2/Fgf10 and p63 genes, which are associated with the NLD and LC hypoplasia in humans. Last, we showed that Prickle 1 expression in the developing tear drainage system is conserved between mice and humans., Conclusions: The study suggests that malformed tear ducts caused by disruption of Prickle 1 underlies the epiphora and precocious eyelid opening.

An 80-year-old man referred with repeated episode of dacryocystitis from the left lacrimal drainage system and palpable swelling. For many years, he has being presented with epiphora unilaterally with chronic dacryocystitis. Investigations with dye-test revealed subocclusion of the natural passage of the tears, and CT and MRI scans revealed solid mass in the lacrimal sac. The lacrimal sac was opened by endonasal endoscopic approach, the sacral mass was identified and completely removed. The histopathological examination showed lacrimal gland in ectopic position. Patient followed for 18 months with complete recovery of symptoms. In our differential diagnosis, the ectopic lacrimal gland is also identified, when a mass in the lacrimal sac and duct is present. Successful surgical excision required considerable multidisciplinary teamwork between ophtalmologist-ENT (Otolaryngologist) and radiologist. Endonasal endoscopic approach is perfectly safe with direct control and ensures a smooth postoperative recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Dry eye disorders are a major health care burden. We previously reported the identification of N -methyl- N -phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine [cystic fibrosis transmembrane conductance regulator (CFTR) act -K267], which activated human wild-type CFTR chloride conductance with EC 50 ∼ 30 nM. Here, we report in vivo evidence for CFTR act -K267 efficacy in an experimental mouse model of dry eye using a human compatible ophthalmic vehicle. Methods: CFTR activation in mice in vivo was demonstrated by ocular surface potential difference (OSPD) measurements. Ocular surface pharmacodynamics was measured in tear fluid samples obtained at different times after topical administration of CFTR act -K267. Dry eye was produced by lacrimal duct cautery (LDC) and corneal epithelial injury and was assessed by Lissamine green (LG) staining. Results: OSPD measurements demonstrated a hyperpolarization of -8.6 ± 3 mV (standard error of the mean, 5 mice) in response to CFTR act -K267 exposure in low chloride solution that was reversed by a CFTR inhibitor. Following single-dose topical administration of 2 nmol CFTR act -K267, tear fluid CFTR act -K267 concentration was >500 nM for more than 6 h. Following LDC, corneal surface epithelial injury, as assessed by LG staining, was substantially reversed in 10 of 12 eyes receiving 2 nmol CFTR act -K267 3 times daily starting on day 2, when marked epithelial injury had already occurred. Improvement was seen in 3 of 12 vehicle-treated eyes. Conclusion: These studies provide in vivo evidence in mice for the efficacy of a topical, human use compatible CFTR act -K267 formulation in stimulating chloride secretion and reversing corneal epithelial injury in dry eye.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making.

Dry eye disease (DED) is a complex and multifactorial disease resulting in a continual cycle of tear hyperosmolarity and inflammation. Patients suffering from DED experience severe pain and visual impairments leading to a reduced quality of life. Aqueous-deficient dry eye (ADDE), mainly caused through a loss of functional lacrimal gland tissue, results in the most severe forms of DED. Despite a high prevalence, the current treatments remain palliative and may be insufficient to alleviate the symptoms. Consequently, investigations on experimental approaches for in situ lacrimal gland regeneration are of great clinical interest. This article reviews the current knowledge about processes involved in lacrimal gland regeneration, about lacrimal gland resident stem cells, and offers deductions about possible concepts for in situ lacrimal gland regeneration. Promising starting points might be the utilization of therapeutic proteins, such as bone morphogenetic protein 7, mesenchymal stem cells (MSC) or MSC-based treatments such as conditioned medium, lyophilized cell extracts or adult acinar cells. This review further summarizes current experimental approaches for the treatment of ADDE in animal models and patients. Approaches investigating side population stem cells, epithelial progenitor cells and MSC showed that the transplantation of these cells had therapeutic effects on ADDE. However, the most promising and best-studied experimental approach is the use of MSC for induction/enhancement of in situ lacrimal gland regeneration. Their immunomodulatory effects, low immunogenicity, promotion of tissue regeneration and involvement during spontaneous lacrimal regeneration are favorable traits for clinical applications. In addition, the efficacy and safety of allogeneic MSC transplantation have already been demonstrated in a small patient cohort.

Purpose : This review examines the broad contexts of the reconstructive and recanalization strategies of the human lacrimal drainage system. Materials and methods : A PubMed search was performed using individually and combination of the terms "lacrimal," "reconstruction", "recanalization," "canaliculus," "canalicular," "stenosis," "obstruction," "block," "drainage," "disorder," "disease," "nasolacrimal duct (NLD)," "endoscopy," "dacryoendoscopy," "trauma," "laceration," "stents," "repair," "tubes," "tear," "eyelid," "Sisler," "trephine," and "trephination". Selections from these lists were the basis of examination of reconstruction and recanalization strategies of multiple lacrimal disorders and their outcomes. Results : The major focus areas of this review are obstructions of the canaliculi and the NLD, traumatic involvement of the lacrimal drainage and their reconstruction strategies, and dacryoendoscopy-guided recanalization of the NLDs. The review found evidence for lack of uniformity in accurately defining the concepts of lacrimal drainage stenosis, partial or complete obstructions. Canalicular obstructions are difficult to manage and outcomes depend on the location of the obstruction. High success rates were reported in cases of canalicular lacerations managed by repair and silicone intubation. Controversies exists in the recanalization strategies involving the NLD. In the absence of any current regenerative strategies, NLD recanalization appears to be promising, but skepticism is well justified until its long-term effects are well known. Conclusions : Reconstructive strategies in canalicular trauma are highly successful. Recanalization strategies for the lacrimal drainage system are promising and there is a need to explore stem cells and regenerative modalities to take the lacrimal drainage science a step forward.

Objective: To assess the functional outcome of three-snip punctoplasty procedure for punctal stenosis at a tertiary care hospital., Methods: The retrospective study was conducted at the Aga Khan University Hospital Karachi, and comprised medical records of all patients aged >18 years who underwent three-snip punctoplasty between January 2013 and December 2017. Data was retrieved on age, gender, diagnosis, signs and symptoms, laterality, date of procedure, resolution of symptoms post procedure, date of last eye followup, symptoms at last follow-up, functional outcome (epiphora at 1 month). SPSS 20 was used for data analysis., Results: Of the 30 patients, 22(73.3%) were females. Overall mean age at the time of punctoplasty was 57.5±15.57 years. Of all the cases, 17(56.7%) had undergone bilateral puntoplasty. At one month, 20(66.7%) patients were completely symptom-free. Females had better results than males but the difference was not significant (p=0.078)., Conclusions: Three-snip punctoplasty was found to be a minimally invasive procedure with good functional outcome that was comparable to other procedures.

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are limited in part due to the lack of informative animal models. The authors recently reported on a method of DED induced by injecting all orbital lacrimal gland (LG) tissues with the lectin concanavalin A. Here, we report a novel model of aqueous-deficient DED based on the surgical resection of all orbital LG (dacryoadenectomy) tissues. Both methods use rabbits because of their similarity to human eyes in terms of the size and structure of the ocular surface. One week after removal of the nictitating membrane, the orbital superior LG was surgically removed under anesthesia, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Dacryoadenectomy induced severe DED, evidenced by a marked reduction in the tear break up time test and the Schirmer's tear test, and significantly increased tear osmolarity and rose bengal staining. Dacryoadenectomy-induced DED lasted at least eight weeks. There were no complications and animals tolerated the procedure well. The technique can be mastered relatively easily by those with adequate surgical experience and appreciation of the relevant rabbit anatomy. Since this model recapitulates the features of human aqueous-deficient DED, it is suitable for studies of ocular surface homeostasis, DED, and candidate therapeutics.

Dry eye disease (DED) is a common multifactorial disease linked to the tears/ocular surface leading to eye discomfort, ocular surface damage, and visual disturbance. Antiinflammatory agents (steroids and cyclosporine A), hormonal therapy, antibiotics, nerve growth factors, essential fatty acids are used as treatment options of DED. Current therapies attempt to reduce the ocular discomfort by producing lubrication and stimulating gland/nerve(s) associated with tear production, without providing a permanent cure for dry eye. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. This review presents an overview, pathophysiology, prevalence and etiology of DED, with an emphasis on preclinical and clinical studies involving the use of nanocarrier systems in treating DED. Lay Summary: Dry eye disease (DED) is a multifactorial disease associated with tear deficiency or excessive tear evaporation. There are several review articles that summarize DED, disease symptoms, causes and treatment approaches. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. Very few review articles summarize the findings on the use of nanotherapeutics in DED. In this review, we have exclusively discussed the preclinical and clinical studies of nanotherapeutics in DED therapy. This information will be attractive to both academic and pharmaceutical industry researchers working in DED therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To summarize the clinical and pathological characteristics of IgG4-related ophthalmic disease (IgG4-ROD) involving the lacrimal gland. Methods: A retrospective case series study. Forty cases (56 eyes) of lacrimal gland lesions were collected in Tianjin Eye Hospital from January 2003 to January 2018 and confirmed by histopathology as lymphocyte and plasma cell infiltration with fibrosis of lacrimal gland tissue, excluding lymphoma, epithelial tumor, mesenchymal tumor and metastasis tumor. The clinical manifestations, serological and imaging examination of the patients were analyzed. Meanwhile, HE staining and immunohistochemical staining of IgG and IgG4 were performed on the pathological specimens. According to the diagnostic criteria, the cases were divided into the IgG4-ROD group and the non-IgG4-ROD group. The clinical and pathological characteristics of the two groups were statistically analyzed by Pearson chi-square and signed-rank test. Results: In the 40 cases (56 eyes), there were 15 cases (25 eyes) of IgG4-ROD and 25 cases (31 eyes) of non-IgG4-ROD. Statistically significant differences were observed between the two groups in the clinical and pathological characteristics (all P< 0.05). About the distribution of eyes position, there were 10 binocular cases and 5 monocular cases in the IgG4-ROD group, and 6 binocular cases and 19 monocular cases in non-IgG4-ROD group (χ 2 =7.111).There were 21 eyes in the IgG4-ROD group and 5 eyes in the non-IgG4-ROD group about ptosis (χ 2 =25.631), 4 eyes in the IgG4-ROD group and 21 eyes in the non-IgG4-ROD group about ocular protrusion (χ 2 =14.992), 23 eyes in the IgG4-ROD group and 15 eyes in the non-IgG4-ROD group about the clear boundary of the tumor (χ 2 =12.069), 4 eyes in the IgG4-ROD group and 18 eyes in the non-IgG4-ROD group about the involvement of other orbital tissues (χ 2 =10.266) and 7 cases in the IgG4-ROD group and 3 cases in the non-IgG4-ROD group about the association with other systemic diseases (χ 2 =6.009). Compared with the non-IgG4-ROD group, the IgG4-ROD group had a heavier lymphocyte and plasma cell infiltration (+++,++,+; 10, 4, 1 vs . 6, 5, 12 eyes, Z= -3.153), and more lymphoid follicles (+++,++,+; 3, 6, 4 vs. 1, 2, 7 eyes, Z= -3.339), interstitial fibrosis was mostly striate (10 vs. 5 eyes, χ 2 =8.711), and there were a large number of IgG4 + plasma cells [96 (67, 135) vs . 4 (0, 12) cells per high power field, Z= -5.271] and ratio of IgG4 + plasma cells/IgG + plasma cells [0.570 (0.500, 0.754) vs. 0.046 (0.000, 0.143), Z= -5.268, all P< 0.05). Among the 10 cases of IgG4-ROD with serological examination, 9 cases showed elevated serum in IgG and IgG4. The ultrasonography and CT findings showed the lacrimal gland lesions in the IgG4-ROD group were mostly spindle or kidney shaped with clear boundaries, while the lesions in non-IgG4-ROD were mostly round or irregular with unclear boundaries. Conclusions: The lacrimal gland lesions of IgG4-ROD are characterized by bilaterally spindle or kidney shaped enlargement with clear boundaries. They are more associates with other systemic diseases. The pathological characteristics are a large number of IgG4 + plasma cells infiltration among the lacrimal gland tissue, interstitial striate fibrosis and a large number of lymphoid follicles. ( Chin J Ophthalmol, 2019, 55: 834-841 ).

Introduction: Corroborating data suggest that the analysis of tear fluid might represent an additional tool in the ophthalmological practice., Areas Covered: The purpose of this review was to sum up the tear protein profiles in healthy and diseased ocular surface and to highlight biomarker usefulness in the early diagnosis as well as at follow-up. This analysis encompasses a deep examination of the protein profile expression under physiological and pathological conditions. Tear protein profile analysis will allow in the near future discriminating between different grades of inflammation, from acute trauma toward immune-, endocrine-, and nervous-related disorders of the ocular surface., Concluding Remarks: The review provides an overview of old and recent findings about inflammatory mediators identified at the ocular surface, under physiological and pathological conditions. To date, the analysis of tear fluid represents a new additional approach for diagnosis and management of ocular surface diseases. Understanding the pathophysiological mechanism could also offer significant advantages to develop strategies addressed to better clarify some complex ocular surface disorders. To sum up, the possibility to provide selective biomarkers as a future target of specific diseases should be considered for supporting diagnosis and management of ocular surface diseases., (© 2018 Wiley Periodicals, Inc.)

Lacrimal occlusion with punctal or canalicular plugs have been used to treat dry eye disease for more than 40 years. Indeed, punctal plugs constitute a safe and effective tool to retain the natural tear film and prolong the effect of tear substitutes. A wide variety of plugs is available, differing in their design, location (punctal versus canalicular) and their resorbability. There indications have increasingly broadened, and they are now one of the treatment options for numerous ocular surface diseases. Current research focuses on using punctal plugs for extended delivery of drugs to the ocular surface. This review addresses physiology of lacrimal drainage, available models of punctal plugs, their indications, practical details of prescribing and placing punctal and canalicular plugs, and possible complications., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Surfactants are complex mixtures of phospholipids and proteins produced by type II alveolar cells of the lungs and play a crucial role in pulmonary physiology. Six types of surfactant proteins (SP) are known; SP-A, SP-B, SP-C, SP-D, SP-G and SP-H. The major role of SP is in reducing surface tension and various immunological functions. SP-A, SP-B, SP-C and SP-D have been demonstrated in the tear film and the epithelium of the lacrimal sac (LS) and nasolacrimal ducts (NLD). All surfactant proteins except SP-G were also isolated from the canalicular tissues. The authors hypothesize that surfactant proteins play a significant role in the pathogenesis of lacrimal drainage disorders; functional nasolacrimal duct obstruction (FNLDO) and infective dacryocystitis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The aim of the present study was to investigate the effects of an amniotic membrane lacrimal stent in the treatment of dry eye syndrome in a perimenopausal rabbit model. In total, 48 healthy female rabbits were randomly divided into four groups (12 rabbits/group): Group A, sham‑operated group; group B, negative control group; group C, sham‑implantation group; and group D, implantation with amniotic membrane lacrimal stents. A Schirmer I test (SIT), corneal fluorescein staining, optical coherence tomography angiography and corneal confocal microscopy were conducted and the biomechanical properties of the amniotic membrane were measured prior to and 2, 4 and 6 weeks after the operations. There were marked differences in the amount of tear secretion and the SIT following the operation compared with prior to the operation. The amount of tear secretion of group B and C was significantly reduced (F=8.894; P=0.0017). Compared with groups A, B and C, group D demonstrated a significant increase in the amount of tear secretion and a significant reduction in SIT (P<0.05). However, there was no statistical difference between the tear secretion of the A, B and C groups (P>0.05). The cornea epithelial of groups A and D was significantly thinner compared with groups B and C. The superior part [superior temporal (ST)5, superior (S)5, superior nasal (SN)5, ST6, S6 and SN6] was significantly thinner compared with the central part of the cornea epithelium. The corneal epithelia of all groups were thin in the center and thick at the edge. At 6 weeks after the operation, group D exhibited a markedly decreased number of anterior stromal luminescent cells, compared with groups A, B and C. Furthermore, the bending degree of corneal stromal neural trunks was significantly improved, and the density, branches and curvature of corneal epithelium sub‑basal nerves ameliorated to a certain extent (P<0.05). Amniotic membrane lacrimal stents demonstrated specific therapeutic effects on dry eye in perimenopausal female rabbits.

Endocrine disruptors are a group of compounds that occur in increasing amounts in the environment. These compounds change the hormone homeostasis of the target organs regulated by those hormones, mostly by binding to their receptors and affecting their signaling pathways. Among the hormones altered by endocrine disruptors are sex hormones, thyroid hormones, and insulin. Studies have documented abnormalities in the reproductive and metabolic systems of various animal species exposed to endocrine disruptors. Endocrine disruptors can play a significant role in ocular diseases once hormone deficiency or excess are involved in the mechanism of that disease. Cataracts, dry eye disease and retinal diseases, such as macular hole and diabetic retinopathy, are some of the frequent problems where hormones have been implicated. We found that some compounds function as endocrine disruptors in the metabolism of body organs and systems. The increasing frequency of dry eye and other ocular diseases indicates the need to better investigate the potential relationships beyond the isolated associations mentioned by patients and documented as rare case reports. The evidence from case-control studies and experimental assays can provide the information necessary to confirm the endocrine effects of these chemicals in the pathophysiology of dry eye disease. We hypothesize that endocrine disruptors may contribute to the increase of ocular diseases, such as dry eye disease, in recent years., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The male Non-Obese Diabetic (NOD) mouse is an established model of autoimmune dacryoadenitis characteristic of Sjögren's Syndrome (SS), but development of diabetes may complicate studies. The Non-Obese Diabetes Resistant (NOR) mouse is a MHC-II matched diabetes-resistant alternative, but development of autoimmune dacryoadenitis is not well-characterized. We compare features of SS in male NOD and NOR mice at 12 and 20 weeks. Stimulated tear secretion was decreased in 12 week NOD relative to BALB/c mice (p < 0.05), while by 20 weeks both NOD and NOR showed decreased stimulated tear secretion relative to BALB/c mice (p < 0.001). Tear CTSS activity was elevated in NOD and NOR relative to BALB/c mice (p < 0.05) at 12 and 20 weeks. While NOD and NOR lacrimal glands (LG) showed increased LG lymphocytic infiltration at 12 and 20 weeks relative to BALB/c mouse LG (p < 0.05), the percentage in NOD was higher relative to NOR at each age (p < 0.05). Gene expression of CTSS, MHC II and IFN-γ in LG were significantly increased in NOD but not NOR relative to BALB/c at 12 and 20 weeks. Redistribution of the secretory effector, Rab3D in acinar cells was observed at both time points in NOD and NOR, but thinning of myoepithelial cells at 12 weeks in NOD and NOR mice was restored by 20 weeks in NOR mice. NOD and NOR mice share features of SS-like autoimmune dacryoadenitis, suggesting common disease etiology. Other findings suggest more pronounced lymphocytic infiltration in NOD mouse LG including increased pro-inflammatory factors that may be unique to this model., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Autoantibodies reactive against Ro52 are present in 70% of Sjögren's syndrome patients and are associated with higher disease severity. However, their role in causing aqueous deficient dry eye, a major cause for morbidity in Sjögren's syndrome, is unclear. To investigate whether immune responses targeting Ro52 contribute towards the dry eye, male and female NZM2758 mice were immunized with recombinant Ro52. Tear production was measured by the phenol red thread test. Sera were analyzed for anti-Ro52 levels by immunoprecipitation. Lacrimal glands were evaluated for inflammatory foci and IgG deposits. Our results showed that, although all mice generated anti-Ro52 antibodies, only females developed a significant drop in tear production. None of the mice developed severe lacrimal gland inflammation, and female mice with anti-Ro52 showed higher levels of IgG deposits within their glands. Passive transfer of anti-Ro52 sera caused reduced tear production in female mice, but not in males. This study demonstrates for the first time that immune responses initiated by Ro52 induce aqueous dry eye, and this may be driven by anti-Ro52 antibodies. Furthermore, the sexual dimorphism in glandular dysfunction suggests that the lacrimal glands in females are more susceptible to autoantibody-mediated injury.

Lacrimal surgery aims to provide a low-resistance tear drainage passage. An assessment of lacrimal resistance guides decisions on surgery. We present results of a modified tear duct irrigation system that reliably measures lacrimal outflow resistance. Patients in a specialist lacrimal clinic had a full work-up to the point of tear duct syringing. The tear ducts were irrigated using a manometric system, which applied a fixed, known head of fluid pressure to a lacrimal cannula. Fluid flow is recorded and the lacrimal resistance derived as fluid pressure/fluid flow (units cmH20 secml-1, for simplicity presented as drops per minute, dpm). Patient groups were: A: Asymptomatic, A1: subgroup where the fellow symptomatic eye had a visible cause for watering, B: external visible cause for watering (ocular surface/lid/punctum), C: no externally visible cause, D: post op DCR, E: post syringing and probing, F: mixed/other. 444 tear ducts were examined. Mean flows (dpm) were: A1 (n = 19) 55; B (n = 183) 46; C (n = 142) 22: D (n = 38) 52. Excluding complete obstruction (n = 29), tear duct syringing only detected 48% of those with impaired manometric flow. Of those with a normal tear duct syringing, 53% had impaired manometric flow; 34% had a flow of 0 dpm. Differences in A1 versus C; B versus C and pre versus post dacryocystorhinostomy were all statistically significant (p < 0.05). The manometric system presented reliably measures lacrimal resistance and provides a substantial increase in sensitivity and specificity over conventional lacrimal syringing.

The purpose of the present studies was to investigate the impact of chronic inflammation of the lacrimal gland, as occurs in Sjögren's syndrome, on the morphology and function of myoepithelial cells (MECs). In spite of the importance of MECs for lacrimal gland function, the effect of inflammation on MECs has not been well defined. We studied changes in MEC structure and function in two animal models of aqueous deficient dry eye, NOD and MRL/lpr mice. We found a statistically significant reduction in the size of MECs in diseased compared to control lacrimal glands. We also found that oxytocin receptor was highly expressed in MECs of mouse and human lacrimal glands and that its expression was strongly reduced in diseased glands. Furthermore, we found a significant decrease in the amount of two MEC contractile proteins, α-smooth muscle actin (SMA) and calponin. Finally, oxytocin-mediated contraction was impaired in lacrimal gland acini from diseased glands. We conclude that chronic inflammation of the lacrimal gland leads to a substantial thinning of MECs, down-regulation of contractile proteins and oxytocin receptor expression, and therefore impaired acini contraction. This is the first study highlighting the role of oxytocin mediated MEC contraction on lacrimal gland function.

Lacrimal canaliculus (LC) has a key role in tear drainage, but it is difficult to evaluate the LC in detail, using the existing examinations. In this study, our novel LC imaging technique provided the high-resolution images of LC in a non-invasive manner. Three-dimensional images of LC were acquired via the palpebral conjunctiva from 20 healthy volunteers (20 eyes) and 10 patients with various lacrimal disorders (10 eyes), using optical coherence tomography (OCT) dacryography (OCTD). The LC images showed morphological differences between the vertical and horizontal segments. The function of LC could be evaluated by measuring the intralumen signal intensity over time after instillation of a contrast agent (2% rebamipide ophthalmic suspension). OCTD clearly visualised the blind extremity of the LC in four patients with punctal obstruction, which was useful for deciding the punctal incision location. In one patient with canalicular obstruction, contrast agent successfully highlighted the LC that had become narrow toward the site of obstruction. Significant differences were not found in the function and morphology of LC between the patients with NLDO and the healthy subjects. OCTD may be a useful tool for LC imaging, because it facilitates quantitative and simultaneous evaluation of LC morphology and function.

Mucosal dryness is a key clinical feature in primary Sjögren's syndrome (pSS) and its assessment relies on both objective measurement of residual secretion and subjective symptoms reported by patients. However, while the objective assessment and grading of glandular dysfunction can be easily performed, the spectrum of clinical symptoms encompassed by the terms 'dry eye' and 'dry mouth' is wide and heterogeneous. Therefore, patient reported outcomes (PROs) for dryness in pSS poorly correlate with the amount of glandular secretion. In addition, subjective dryness is not correlated with the severity of systemic disease and severely affects the patient quality of life even in presence of active extraglandular manifestations. The purpose of this review article is to provide an overview of glandular dysfunction in pSS as well as the impact of discrepancy between objective assessment, subjective symptom and extraglandular disease activity on disease management.

The primary objective of the present study was to highlight the current state of research on the pathology of the lacrimal organs based on the results of the analysis of the relevant publications in the domestic and foreign scientific literature. Special attention in this review is given to the problems of diagnostics, indications for the probing, the treatment and stenting strategies. The authors report their original observations contributing to the better understanding of the anatomical features of the nasolacrimal passages. In addition, the data on the principal pathogenic agents are presented together with certain peculiarities of the surgical treatment of the pathology under consideration.

Purpose: The aim is to analyze the influence of the location of lacrimal canalicular laceration over the eventual anatomical and functional success after surgery., Methods: Retrospective, observational study of proximal canalicular laceration (PCL) and distal canalicular laceration (DCL) repairs by a single surgeon (MS). The distance between lacrimal punctum and the lateral canalicular lacerated end was defined as proximal (<6 mm) and distal (≥6 mm). The operation theater setup, microscopic magnified view, local adrenaline, and pigtail probe were used to locate the medial canalicular lacerated end. All patients underwent lacrimal stenting and the stents were removed after 3 months (12th week visit). After stent removal, a fluorescein dye disappearance test and lacrimal irrigation were performed to assess the anatomical and functional success of the operation., Results: Of 36 canalicular lacerations, 30 (83.33%) were monocanalicular lacerations which were repaired using monocanalicular stents. Of 6 (16.67%) bicanalicular lacerations, three were repaired using bicanalicular stents while in the remaining three, one monocanalicular stent was placed in each lacerated canaliculi. The medial cut end was identified by magnified visualization in 27 (75%), with adjunctive local adrenaline in four (11.11%) and pigtail probe in five (13.89%) patients. The mean post stent removal follow-up was 44 weeks. The DCL (n = 24, 66.67%) showed better functional and complete success as compared to PCL (75% vs. 33.33%, P = 0.03). Eight (22.22%) had spontaneous stent extrusion, two (5.56%) had loop prolapse, four (11.11%) had punctum granuloma, and three (8.33%) had medial canthus dystopia., Conclusion: The location of canalicular laceration may help to prognosticate the functional and qualified success rate. We experienced better-qualified success in the distal canalicular laceration group.

Purpose: To estimate the prevalence of external punctal stenosis (EPS) in the elderly population and investigate associated factors., Methods: A total of 278 patients ≥65 years of age were evaluated for evidence of EPS from January to July 2016. Associated systemic, ocular, demographic, and lifestyle factors were investigated. Multiple logistic regression analyses were applied to evaluate the factors related to having EPS. P values <0.05 were considered statistically significant., Results: The prevalence of EPS in this study population was 63.3%, with a mean age of 70.67 ± 7.85 (65-92 years). The ocular factor that was most commonly related to EPS was chronic blepharitis (48.9%). EPS was also associated with taking glaucoma medications (95% CI, 0.08-0.96, p=0.043), smoking history (95% CI, 0.13-0.84, p=0.021), ectropion (95% CI, 0.004-0.26, p=0.001), complaints of tearing (95% CI, 1.11-3.52, p=0.02), and outdoor occupational activity (95% CI, 3.42-9.97, p<0.05)., Conclusions: EPS is more common in elderly patients than in the general population. Outdoor occupational activity, taking antiglaucomatous medications, ectropion, and smoking are significantly associated with EPS. In addition, surgical treatment decisions should be made after complete evaluation and interviewing the patients.

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology., Competing Interests: The authors declare no conflict of interest.

Objective: Our study aimed at evaluating ocular findings and structural changes in coal mine workers who were chronically exposed to coal mine dust and diagnosed with pneumoconiosis., Methods: Ocular findings of 161 eyes of 81 patients diagnosed with pneumoconiosis who had previously worked or are currently working in coal mines were analyzed. Forty-six coal mine workers and sex matched healthy people (n = 20) participated in the study. Workers who had early changes of pneumoconiosis were included in Group 1 (n = 17), workers diagnosed with pneumoconiosis were included in Group 2 (n = 29), and healthy subjects were included in Group 3 (n = 20). Outcome measures were the difference in peripapillary retinal nerve fiber layer (RNFL) thickness, choroidal thickness (CT), central macular thickness (CMT) and tear function tests between the groups., Results: RNFL thickness values in Group 1 and 2 were lower than in Group 3, the control group, in all quadrants except the temporal quadrant. However, there was no statistically significant difference in peripapillary RNFL thickness values in any quadrants among the three groups (p > 0.05). Central subfoveal choroidal thickness and CMT measurements were thinner in Group 1 and 2 than in the control group. However, this difference among groups was not statistically significant (p > 0.05). Mean schirmer's test result was 8.8 ± 1.6 mm in group 1, 7.1 ± 1.8 mm in Group 2 and 11.5 ± 3.6 mm in the control group. Mean tear break up time (BUT) test result was 7.1 ± 1.3 seconds (sec) in Group 1, 6.5 ± 1.8 sec in Group 2 and 10.4 ± 2.9 s in the control group. The Schirmer's test and BUT test results were both statistically significantly lower in coal mine workers (Group 1 and 2) compared to the control group. Group 1 and Group 2 did not show statistically significant difference in terms of Schirmer's test and BUT test results., Discussion: The association between pneumoconiosis and coal mine dust contiguity is thought to be due to the effect of coal dust by producing chronic inflammation. In addition, there are several trace elements in coal dust which are toxic to vital tissues. In this study, ocular findings suggest that systemic levels of trace elements and chronic inflammation may not reach to a level that influences ocular structures. Nonetheless, tear functions seem to be affected in coal mine workers., Conclusion: This study suggests that the systemic effect of coal mine dust in ocular structures is not evident. However, direct contact with coal mine and fume leads to a decrease in tear function tests.

Background: Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Lacrimal gland function has been shown to decrease with aging, a known potent risk factor for dry eye. We have previously found that orally administrated royal jelly (RJ) restored tear secretion in a rat model of dry eye., Methods and Findings: We examined the effects of RJ oral administration on dry eye in this prospective, randomized, double-blind, placebo-controlled study. Forty-three Japanese patients aged 20-60 years with subjective dry eye symptoms were randomized to an RJ group (1200 mg/tablet, six tablets daily) or a placebo group for 8 weeks. Keratoconjunctival epithelial damage, tear film break-up time, tear secretion volume, meibum grade, biochemical data, and subjective dry eye symptoms based on a questionnaire were investigated at baseline, and at 4 and 8 weeks after intervention. Adverse events were reported via medical interviews. In the RJ group, tear volume significantly increased after intervention (p = 0.0009). In particular, patients with a baseline Schirmer value of ≤10 mm showed a significant increase compared with baseline volume (p = 0.0005) and volume in the placebo group (p = 0.0051). No adverse events were reported. We also investigated the effect of RJ (300 mg/kg per day) administration using a mouse model of dry eye. Orally repeated administration of RJ preserved tear secretion, potentially through direct activation of the secretory function of the lacrimal glands., Conclusion: Our results suggest that RJ improves tear volume in patients with dry eye., Trial Registration: Registered NO. the University Hospital Medical Information Network in Japan (UMIN000014446)., Competing Interests: KT received the Yamada Research Grant. SI manages the Haneginomori Eye Clinic. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

PurposeEndonasal dacryocystorhinostomy (END-DCR) is a relatively novel approach that has recently been shown in some studies to provide similar success rates to the more traditional external approach for the treatment of nasolacrimal duct obstruction (NLDO). However, a range of success rates using this approach are reported within the literature and the majority of oculoplastic surgeons are still favouring the external approach. The purpose of this study was to review the anatomical and subjective success rates of END-DCRs performed over a 7-year period.Patients and methodsWe provide a review of the success rates of 288 END-DCRs for the treatment of acquired NLDO performed over a 7-year period by a single oculoplastic surgeon in Sydney, Australia. We describe the operative technique used and define anatomical success as demonstrated patency of the nasolacrimal drainage system at 10 weeks postoperatively while subjective success is defined as complete resolution or significant improvement of symptoms as reported by patients at the same time point.ResultsIn our study, we were able to demonstrate that out of 288 END-DCRs, an average anatomical success rate of 89.6% and an average subjective success rate of 81.3% were achievable.ConclusionsWe conclude that the success rates using our endonasal approach remain similar to those obtained using the external approach, as reported within the literature, and may be considered as a primary treatment option for acquired NLDO.

Introduction: To evaluate meibomian gland function, changes of lacrimal tears and ocular surface parameters and tear inflammatory mediators following cataract surgery., Methods: 48 eyes of 34 patients who underwent uncomplicated phacoemulsification were involved and divided into 2 groups with those who had preexisting dry-eye before cataract surgery and those who did not. Ocular symptom score, Schirmer I test, tear film break-up time (TBUT), corneal sensitivity threshold, corneal staining, inflammatory cytokine activities, lid margin abnormalities, meibum expressibility, meibum quality and meibomian gland imaging were evaluated preoperatively, at 1 day, 1 and 2 months postoperatively., Results: Ocular symptom scores were worse at 1 and 2 months postoperatively but, TBUT, corneal staining score and corneal sensitivity threshold showed gradual improvements at 1 month and 2 months postoperatively (p<0.05, respectively). Interestingly there were statistically significant improvements in TBUT, corneal staining score and corneal sensitivity threshold at 1 month postoperatively when topical eye drops were used compared to the period without topical therapy which is the months 2 postoperatively. There were statistically significant decreases in IL-1β, IL-6, IL-8, MCP-1, TNF-α and IFN-γ concentrations at 1 and 2 months postoperatively. Lid margin abnormalities, meibum quality and expressibility scores increased significantly (p < 0.05, respectively) at postoperative period. Compared with the no dry eye group, dry eye group revealed significantly higher ocular symptom scores, lower TBUT, higher lid margin abnormalities, meibum quality and expressibility scores after cataract surgery. There were significant correlations between IL-6 and parameters of dry eye, and between MGD parameters and ocular symptom scores., Conclusions: Our study revealed that meibomian gland function is influenced after cataract surgery accompanying structural changes and these were correlated with increased ocular symptom scores. Therefore, it could elucidate the development of dry eye related to cataract surgery., Competing Interests: The authors have declared that no competing interests exist.

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film.

In this article, the authors attempt to determine the retention rate and benefits of Painless Punctal Plug F(TM) placed in patients diagnosed with dry eye. This is a prospective, observational cohort study. Forty patients diagnosed with dry eye underwent Painless Punctal Plug F placement in the inferior puncta (80 puncta) in a private clinic from January 2010 to July 2012. Patients were then followed up monthly for seven months taking note of plug retention, spontaneous plug loss, and complications. Retention rates of patients with mean age of 58.6 years were 100% after one month, 98.75% after two months, 96.25% after three months, 95% after four months, 93.75% after five months, and 92.5% after seven months. In the 80 plugs, three plugs underwent spontaneous punctal plug loss and three plugs were removed due to local discomfort. In total, 74 out of 80 plugs remained intact after seven months of follow-up. Kaplan-Meier analysis showed that there was propensity for spontaneous punctal plug loss or plug removal in the Sjogren group as compared to the non-Sjogren group. No complications were noted such as epiphora, local inflammatory reaction, nor canalicular pyogenic granuloma except for local discomfort. This study showed that Painless Punctal Plug F has a high retention rate with the following benefits, it has one-size, fitted for small to medium puncta; extended round end which made prior dilation unnecessary and once inserted, the soft round bulb fits snugly inside the punctum preventing plug loss.

Purpose: To compare the results of tear film and lacrimal drainage system tests between anophthalmic socket and normal eye and assess discharge characteristics and frequency of prosthesis removal (questionnaire), eyelid function, and meibomian glad dysfunction (MGD)., Design: Prospective masked case control., Methods: Subjects (≥6 years and ≥6 months of wearing prosthesis) with unilateral acquired anophthalmic socket discharge were included. Excluded was ocular adnexal abnormality of any reason and incomplete tests. The subjective questionnaire was completed. Blinking rate, lagophthalmos, eyelid laxity, MGD, Schirmer test, tear meniscus height, and dye disappearance test were assessed by a masked examiner. Another masked examiner performed an irrigation test 1 week later and interpreted the scintigraphy images at the end of the study., Results: Included were 50 subjects (mean age: 31.3 years, mean prosthesis wear: 96.1 months). Discharge was frequent or very frequent in 85%, mucoid or mucopurulent in 90%, and moderate to severe in 86% of the subjects. MGD in 58%, lagophthalmos in 80%, and eyelid laxity in 46% were observed. Anophthalmic socket sides showed a significantly lower tear production and higher tear drainage obstruction. Subjects with frequent prosthesis removal had a significantly (P = .02) greater lagophthalmos and blinking rate (P = .04). The blinking rate was also significantly greater in subjects with higher frequency of discharge (P = .04)., Conclusion: Tear film impairment (aqueous and lipid) and lacrimal drainage obstruction should be considered in subjects with anophthalmic socket discharge. A significantly higher blinking rate and lagophthalmos were found in subjects with higher frequency of prosthesis removal., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: This study was performed to explore the effects of hormone replacement therapy (HRT) on aqueous tear production and tear quality in dry eye syndrome (DES) patients of different ages., Methods: Eighty-eight women with DES at least one year after spontaneous menopause were randomly divided into the HRT group that were treated with orally estrogen and medroxyprogesterone acetate or a control group that did not receive any treatment. The aqueous tear production and tear quality were measured by Schirmer test and tear film break up time (TBUT) before and after one month of treatment. The subjects were subdivided according to age; the HRT group was divided into groups A (age range: 44-49 years) and B (age range: 50-57 years), and the controls were divided into groups C (age range: 46-49 years) and D (age range: 50-55 years). The changes in results of Schirmer test and TBUT before and after treatment were compared within each group and were correlated with the age of the participants., Results: After one-month follow-up, HRT use improved the Schirmer test but the effect was significant only for participants less than 50 years old. The improvement in Schirmer test result was negatively correlated with the age of the participants. The TBUT did not change significantly within each group after HRT use., Conclusions: HRT use may improve aqueous tear production but not the quality of tears in DES, and the effect on tear production is dependent on age., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the diagnostic value and treatment guidance of lacrimal magnetic resonance hydrography (LMRH) and lacrimal endoscopy examination in lacrimal duct obstruction., Methods: A retrospective analysis of clinical and imaging data of 59 patients with epiphora who had LMRH examination in Tongji Hospital during June 2013 and January 2014. Multiplanar reconstruction (MPR) and maximum intensity projection (MIP) were used to process the three dimensions T2-weighted images (T2WI). The size of lacrimal sac, lacrimal mucosal lesions and the obstructed plane of nasolacrimal duct were observed. The lacrimal irrigation results were used as gold standard. The sensitivity, specificity, accuracy of LMRH in diagnosis of lacrimal duct obstructive diseases and the consistency between the two methods were analyzed. In addition, 22 cases had lacrimal endoscopy examination in less than half month after MRD. The results of lacrimal endoscopy were compared with LMRH images. The treatment method was made according to the results of LMRH and lacrimal endoscopy., Results: According to the results of lacrimal irrigation, among 78 eyes of 59 patients, 2 eyes were diagnosed as lacrimal canalicular obstruction (2.6%, 2/78), 8 eyes were diagnosed as nasolacrimal duct stenosis (10.3%, 8/78), 24 eyes were diagnosed as nasolacrimal duct obstruction (30.8%, 24/78), 44 eyes were diagnosed as nasolacrimal duct obstruction accompanied with chronic dacryocystitis (56.4%, 44/78). The other 40 eyes were negative controls. LMRH had a high degree of consistency with lacrimal irrigation in diagnosis of lacrimal duct obstructive diseases. The value of Kappa was 0.963 (P= 0.026). The sensitivity of MRD in diagnosis of lacrimal duct obstructive diseases was 97.4%, the specificity was 100%, the accuracy was 98.3%, the positive predictive value was 100% and the negative predictive value was 95.2% . According to 40 eyes of the control group, the mean value of the maximum cross-sectional area of the lacrimal sac was: (10.9 ± 0.4) mm(2). Twenty-two eyes underwent lacrimal endoscopy examination and the endoscopic findings were consistent with LMRH diagnosis. The lesions in the lacrimal duct displayed more clearly and intuitively than the LMRH, while LMRH had its unique advantages in showing the size of lacrimal sac, the mucosal thickness of lacrimal duct, large foreign bodies and lesions around the lacrimal duct. According to the results of LMRH and lacrimal endoscopy, 2 eyes of canalicular obstruction, 8 eyes of nasolacrimal duct stenosis, 20 eyes of nasolacrimal duct obstruction underwent lacrimal probing and stent implantation. Four eyes of nasolacrimal duct obstruction had drug treatment under lacrimal endoscopy. Thirty-eight eyes of chronic dacryocystitis underwent endonasal dacryocystorhinostomy. The other 6 eyes of chronic dacryocystitis underwent stent removal combined with endonasal dacryocystorhinostomy., Conclusions: LMRH is a noninvasive and reliable method to examine the lacrimal duct obstruction. It can better display the size of lacrimal sac, lacrimal mucosal thickness and surrounding soft tissues of lacrimal duct. It is also a good complementary method of lacrimal endoscopy and has guiding significance for individualized treatment in patients with lacrimal duct obstruction.

Purpose: To evaluate the efficacy of tightening of lateral portion of orbicularis oculi muscle in patients with functional nasolacrimal duct obstruction (FNLDO)., Methods: This is an interventional cross-section study for evaluation of effect of orbicularis oculi tightening procedure in patients with FNLDO. Patients with unexplained epiphora, open lacrimal system in syringing and evidences of lacrimal pump weakness in lacrimal scintigraphy underwent surgery. In this procedure, a stripe of preseptal and pretarsal orbicularis muscle was dissected, slightly resected and secured to the periosteum of lateral orbital rim. Each subject completed a questionnaire about the intensity of epiphora before surgery and 1, 3 and 6 months after surgery. Furthermore, fluorescein dye disappearance test (FDDT) was performed before surgery and repeated in the follow-up visits. At last visit, the pre- and post-operative data were analyzed and compared., Results: Fifteen eyes of 12 patients (5 males and 7 females) with the mean age of 56.7 years included in the study. Severity of epiphora and tearing effect on daily life were significantly improved following the operation. FDDT result was improved significantly after 1 month follow-up in all eyes (15 eyes), at 3 months follow-up in 80% of eyes (12 eyes) and at the end of the 6th month in 66.7% of eyes (10 eyes). Subjective and objective success rates were 87% and 80%, respectively. No significant complications or side-effects were observed., Conclusion: Tightening of lateral portion of preseptal and pretarsal orbicularis muscle seems an effective, safe, and easy procedure to decrease epiphora in patients with FNLDO.

Background: Dacrocystorhinostomy (DCR) is an operation used to treat nasolacrimal duct obstruction. Essentially there are two approaches: external and endoscopic. Several modalities are used in endoscopic DCR; all aiming to improve success rate, reduce complications, and shorten operative time. Both kerrison punch and drill are widely used in endoscopic DCR with non-conclusive knowledge about differences in operative details as well as on the outcome. The aim of this study is to compare between powered (drill) and non-powered (kerrison punch) DCR to clarify the superiority of one over the other., Methods: A retrospective chart review of 59 patients who underwent endoscopic DCR procedure at our institution from June 2013 until July 2014 (34 kerrison punch and 32 powered drill). Operative details, surgical outcome and complications were compared between both groups., Results: A total of 66 endoscopic DCRs were performed on 59 patients. Procedure success rate among kerrison punch group was 87.88% vs. 90.9% in powered drill group (p = 0.827), while complications for both groups were statistical not significant (p = 0.91). The mean operating time among kerrison punch group was significantly lower than in powered drill group (75 min vs. 125 min, p = 0.0001)., Conclusion: Kerrison punch showed significant reduction in operating time when compared to powered drill for endoscopic DCR. No statistically significant difference was found between both groups regarding procedures' success rate and complication.

Purpose: This study reports tear compensation observed in rabbits with bilateral resection of main lacrimal gland (LG) and explored the potential mechanisms., Methods: Dry eye conditions were created by resection of nictitating membrane (NM), Harderian gland (HG), and main LG in eight (16 eyes) male New Zealand White rabbits. In addition to Schirmer test, Periodic acid-Schiff (PAS) staining, and ocular surface staining with fluorescein and rose Bengal, conjunctival impression cytology was employed before and up to 4 months after excision (AE). Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), expression of inflammatory biomarkers (IL-1β, TNF-α, and matrix metalloproteinase-9) were monitored. Further, involvement of ionic and water transporters were investigated in conjunctival epithelium., Results: Significant dry eye phenotypes in rabbits were observed 1 month AE, which corroborated with elevated biomarker mRNA expression. However, Schirmer test score and goblet cell numbers never decreased AE in conjunctival epithelium. Moreover, ocular surface staining, and biomarker expression declined to baseline in over 4 months AE. No upregulation was observed of the following conjunctival ionic transporters: cystic fibrosis transmembrane conductance regulator, sodium potassium chloride cotransporters, sodium potassium ATPase, and epithelial sodium channels. Instead, aquaporin (AQP) 4 and AQP5 were upregulated. Immunolocalization and immune blotting of AQP4 was demonstrated in rabbit conjunctival epithelium., Conclusions: In the absence of NM, HG, and main LG in rabbits, tear secretion was not decreased and significant improvement of dry eye phenotypes observed with time AE. Conjunctival AQPs are possibly involved in a compensatory tear fluid production.

Chronic graft-versus-host disease (cGVHD) is a serious complication known to occur after allogeneic hematopoietic stem cell transplantation. Clinical manifestation includes inflammation and fibrosis. Many peripheral tissues are capable of generating the renin-angiotensin system (RAS) components, called the tissue RAS, and have various roles in tissue-specific physiological and pathological functions of inflammation and fibrosis. This article reviews evidence for the presence of the tissue RAS in the normal mouse lacrimal gland, the role of the tissue RAS in the fibrotic pathogenesis of the lacrimal gland in cGVHD model mice, and the effect of angiotensin II receptor blockers on preventing lacrimal gland fibrosis. B10.D2→BALB/c (H-2d) major histocompatibility complex-compatible, minor histocompatibility antigen-mismatched mice were used as a model of cGVHD, which reflects the clinical and pathological symptoms of human cGVHD. We also describe the localization of RAS components in the normal mouse lacrimal gland. In addition, we characterize the inflammatory and fibrotic changes of the lacrimal gland in cGVHD model mice, demonstrate that fibroblasts strongly express angiotensin II, angiotensin II type 1 receptor (AT1R), and angiotensin II type 2 receptor, and show that mRNA expression of angiotensinogen increased in the lacrimal gland of cGVHD model mice. Inhibitory experiments revealed that lacrimal gland fibrosis was suppressed in mice treated with an AT1R blocker, but not in mice treated with an angiotensin II type 2 receptor blocker. Hence, we conclude that the tissue RAS is involved in the fibrotic pathogenesis of the lacrimal gland and that AT1R blockers have a therapeutic effect on lacrimal gland fibrosis in cGVHD model mice.

Purpose: Some dry eye disease (DED) patients have sensitized responses to corneal stimulation, while others experience hypoalgesia. Many patients have normal tear production, suggesting that reduced tears are not always the cause of DED sensory dysfunction. In this study, we show that disruption of lacrimal innervation can produce hypoalgesia without changing basal tear production., Methods: Injection of a saporin toxin conjugate into the extraorbital lacrimal gland of male Sprague-Dawley rats was used to disrupt cholinergic innervation to the gland. Tear production was assessed by phenol thread test. Corneal sensory responses to noxious stimuli were assessed using eye wipe behavior. Saporin DED animals were compared to animals treated with atropine to produce aqueous DED., Results: Cholinergic innervation and acetylcholine content of the lacrimal gland were significantly reduced in saporin DED animals, yet basal tear production was normal. Saporin DED animals demonstrated normal eye wipe responses to corneal application of capsaicin, but showed hypoalgesia to corneal menthol. Corneal nerve fiber density was normal in saporin DED animals. Atropine-treated animals had reduced tear production but normal responses to ocular stimuli., Conclusions: Because only menthol responses were impaired, cold-sensitive corneal afferents appear to be selectively altered in our saporin DED model. Hypoalgesia is not due to reduced tear production, since we did not observe hypoalgesia in an atropine DED model. Corneal fiber density is unaltered in saporin DED animals, suggesting that molecular mechanisms of nociceptive signaling may be impaired. The saporin DED model will be useful for exploring the mechanism underlying corneal hypoalgesia.

Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To investigate parameters of ocular surface disease in C57BL/6.NOD-Aec1Aec2 (Aec) mice with aging and their correlation with development of Sjögren syndrome (SS)-like lacrimal gland (LG) disease., Methods: Aec and C57BL/6 wild-type (B6) female mice were evaluated at 4, 12, and 20 weeks of age. Whole LG and eyes and adnexa were excised for histology and gene expression analysis and evaluated by flow cytometry and immunohistochemistry. Tear volume and goblet cell density was measured. Quantitative PCR evaluated T-cell-related cytokine expression in cornea and conjunctiva., Results: Both strains showed age-related conjunctival goblet cell loss that was more pronounced in the Aec strain and significantly greater than in B6 mice at 12 weeks. This was accompanied by CD4+ T-cell infiltration of the conjunctiva that was greater in Aec strain at 20 weeks. Aec mice had higher levels of IL-17A, IL-17R, IL-1α, IL-1β, and TNF-α in the conjunctiva, and they significantly increase with aging. Aec mice had greater lymphocytic infiltration of the LG and conjunctiva at 20 weeks that consisted of a mixture of CD4+ and CD8+ cells. Flow cytometry showed a significant increase in CD4+ T cells in Aec LG compared to B6 mice. Tear volume was significantly increased in both strains at 20 weeks., Conclusions: Aec mice developed greater conjunctival goblet cell loss associated with lymphocytic infiltration of the LG and conjunctiva with aging. Increased expression of certain T helper or inflammatory cytokines in these tissues was observed in Aec mice. The conjunctival disease appeared to be due to inflammation and not a decrease in tear volume.