Schirmer tear test-1 with open or closed eyelids: An evaluation in brachycephalic and nonbrachycephalic dogs.

PURPOSE: Assess aqueous tear production when measured with the dogs' eyelids open or closed. METHODS: Thirty healthy dogs (15 Shih Tzus, 15 Labrador retrievers) were recruited. With the order of testing randomized for each dog, two sessions (separated by 30 min) of STT-1 testing were performed with the dogs' eyelids closed or open. Schirmer strip wetness (every 10 s for 60 s) and number of time(s) the strip dislodged during testing were recorded in each eye. Preferred STT-1 method was surveyed via a global Listserv of the veterinary ophthalmology community. RESULTS: STT-1 values were significantly higher in closed versus open eyes in Shih Tzus (18.6 ± 2.7 mm/min vs. 16.3 ± 2.5 mm/min; p = .002) and Labrador retrievers (21.6 ± 2.9 mm/min vs. 17.8 ± 3.2 mm/min, p < .001), findings that were also significant at times <60 s for either breed (p ≤ .004). Schirmer strips dislodged from six dogs with open eyelids and no dogs with closed eyelids. Maximal STT-1 difference with closed versus open eyelids was 13 mm/min in Labrador retrievers and 7 mm/min in Shih Tzus. Survey results from 275 veterinarians showed STT-1 performed with "closed eyelids" (38.5%), "open eyelids" (26.9%), or "never paid attention, sometimes closed, sometimes open" (34.6%). CONCLUSIONS: Eyelids status (closed or open) during STT-1 testing had a significant impact on aqueous tear secretion in brachycephalic and nonbrachycephalic dogs, highlighting the importance of consistency when repeating STT-1 in a canine patient. STT-1 differences are likely due to sustained reflex tearing throughout the test duration when the dogs' eyelids are closed.

Potential Therapeutic Role of Pituitary Adenylate Cyclase-Activating Polypeptide for Dry Eye Disease.

Dry eye disease (DED) is caused by a reduction in the volume or quality of tears. The prevalence of DED is estimated to be 100 million in the developed world. As aging is a risk factor for DED, the prevalence of DED is expected to grow at a rapid pace in aging populations, thus creating an increased need for new therapies. This review summarizes DED medications currently in clinical use. Most current medications for DED focus on stimulating tear secretion, mucin secretion, or suppressing inflammation, rather than simply replenishing the ocular surface with moisture to improve symptoms. We recently reported that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) induces tear secretion and suppresses corneal injury caused by a reduction in tears. Moreover, it has been reported that a PACAP in water and a 0.9% saline solution at +4 °C showed high stability and achieved 80-90% effectiveness after 2 weeks of treatment. These results reveal PACAP as a candidate DED medication. Further research on the clinical applications of PACAP in DED is necessary.

Effect of Aucubin-Containing Eye Drops on Tear Hyposecretion and Lacrimal Gland Damage Induced by Urban Particulate Matter in Rats.

Exposure to particulate matter is a causative factor of dry eye disease. We aimed to investigate the beneficial effect of eye drops containing aucubin on dry eye disease induced by urban particulate matter (UPM). Dry eye was induced in male SD rats (6 weeks old) by topical exposure to UPM thrice a day for 5 d. Eye drops containing 0.1% aucubin or 0.5% aucubin were topically administered directly into the eye after UPM exposure for an additional 5 d. Tear secretion was evaluated using a phenol red thread tear test and corneal irregularity. The oxidative damage in the lacrimal gland was evaluated using TUNEL and immunohistochemical staining. The topical administration of aucubin significantly attenuated UPM-induced tear hyposecretion (control group: 9.25 ± 0.62 mm, UPM group: 4.55 ± 0.25 mm, 0.1% aucubin: 7.12 ± 0.58 mm, and 0.5% aucubin: 7.88 ± 0.75 mm) and corneal irregularity (control group: 0.00 ± 0.00, UPM group: 3.40 ± 0.29, 0.1% aucubin: 1.80 ± 0.27, and 0.5% aucubin: 1.15 ± 0.27). In addition, aucubin also reduced the UPM-induced apoptotic injury of lacrimal gland cells induced by oxidative stress through the increased expression of HMGB1 and RAGE. These findings indicate that the topical administration of aucubin eye drops showed a beneficial effect against UPM-induced abnormal ocular changes, such as tear hyposecretion and lacrimal gland damage. Therefore, our results reveal the pharmacological activities of aucubin in dry eye disease.

[Changes in precorneal tear film and ocular surface in keratoconic patients after corneal collagen cross-linking]. / Izmenenie sostoyaniya prerogovichnoi sleznoi plenki i glaznoi poverkhnosti posle krosslinkinga rogovichnogo kollagena pri keratokonuse.

The article reviews the current available data on the signs and symptoms of dry eye syndrome (DES) in patients with keratoconus (KC), describes the clinical features of DES in KC patients and the morphological features of this type of keratectasia that lead to manifestations of the «dry eye¼, and highlights the risk factors, consequences of therapeutic measures, concomitant ophthalmological and general somatic diseases that contribute to the development of DES in KC.

Circadian clock regulates tear secretion in the lacrimal gland.

Although diurnal variations have been observed in tear film parameters in various species, the molecular mechanisms that control circadian tear secretion remain unclear. The aim of our study was to evaluate the role of clock genes in the lacrimal gland (LG) in regulation of tear secretion. Tear volume was measured by cotton thread test in core clock genes deficient (Cry1-/-Cry2-/--) mice which are behaviorally arrhythmic. Real-time quantitative RT-PCR was used to examine expression profiles of core clock genes in the LG including Per1, Per2, Per3, Clock, Bmal1. All experiments were performed under a 12 h of light and 12 h of darkness (LD) and constant dark (DD) conditions. Under both LD and DD conditions, diurnal and circadian rhythms were observed in tear secretion of wild-type mice with tear volume increased in the objective and subjective night while disruption in diurnal and circadian variations of tear secretion were found in Cry1-/-Cry2-/--mice. In wild-type mice, the expression level of major clock genes in the LG showed oscillatory patterns under both LD and DD conditions. In contrast, expression clock genes in the lacrimal gland of Cry1-/-Cry2-/-- mice showed complete loss of oscillation regardless of environmental light conditions. These findings confirmed the presence of diurnal and circadian rhythms of tear secretion and provided evidences supporting a critical role for the clock in the control of tear secretion.

Aged Mice Devoid of the M3 Muscarinic Acetylcholine Receptor Develop Mild Dry Eye Disease.

The parasympathetic nervous system is critically involved in the regulation of tear secretion by activating muscarinic acetylcholine receptors. Hence, various animal models targeting parasympathetic signaling have been developed to induce dry eye disease (DED). However, the muscarinic receptor subtype (M1-M5) mediating tear secretion remains to be determined. This study was conducted to test the hypothesis that the M3 receptor subtype regulates tear secretion and to evaluate the ocular surface phenotype of mice with targeted disruption of the M3 receptor (M3R-/-). The experimental techniques included quantification of tear production, fluorescein staining of the ocular surface, environmental scanning electron microscopy, assessment of proliferating cells in the corneal epithelium and of goblet cells in the conjunctiva, quantification of mRNA for inflammatory cytokines and prooxidant redox enzymes and quantification of reactive oxygen species. Tear volume was reduced in M3R-/- mice compared to age-matched controls at the age of 3 months and 15 months, respectively. This was associated with mild corneal epitheliopathy in the 15-month-old but not in the 3-month-old M3R-/- mice. M3R-/- mice at the age of 15 months also displayed changes in corneal epithelial cell texture, reduced conjunctival goblet cell density, oxidative stress and elevated mRNA expression levels for inflammatory cytokines and prooxidant redox enzymes. The findings suggest that the M3 receptor plays a pivotal role in tear production and its absence leads to ocular surface changes typical for DED at advanced age.

Reference values of Schirmer tear test in sheep and the effect of season on the test results.

The aim of this study was to determine the reference range of Schirmer tear test (STT) values in sheep using Greek indigenous and mixed breeds and to investigate the potential effect of breed and season on these values. Ninety (30 Chios, 30 Florina and 30 Lacaune mixed breed) ewes aged 2 years or more were used for the study. The aqueous portion of the tear film was measured using Schirmer tear test (STT) commercial strips bilaterally by the same investigator with the animal in standing position. The average STT value recorded was 18.45 ± 3.93 mm/min and the range 10.8-26.2 mm/min. STT was significantly affected by the season and the recorded values were significantly higher in summer compared to winter. The breed had no significant effect on tear secretion. The results of the present study provide a reference range of STT values in sheep and indicate that tear secretion is significantly affected by the season.

Effect of sedation with butorphanol on variables pertaining to the ophthalmic examination in dogs.

OBJECTIVE: To evaluate whether sedation with intramuscular butorphanol can interfere with different variables of the ocular examination in dogs. ANIMALS: Twenty-two beagles without ophthalmic abnormalities. PROCEDURES: Each dog was examined 20 min prior to and again just before administration of butorphanol to establish baseline data. The globe and nictitating membrane position was evaluated, and the following were recorded: menace response, dazzle reflex, corneal blink reflex, phenol red thread tear test (PRT), Schirmer tear test-1 (STT-1), pupil size (PS) measurement, and rebound tonometry. Then, butorphanol was injected intramuscularly at a dose of 0.2 mg/kg and these procedures were repeated 10, 20, 30, and 45 min postadministration. A sedation score graded 0 to 3 was also established at these time points. Statistical analyses were performed on quantitative data using ANOVA. RESULTS: The sedative effect was not associated with any changes in globe and nictitating membrane position; did not affect the results of the menace response, dazzle reflex, and corneal blink reflex; and had no significant effect on PRT values. However, butorphanol administration was associated with a statistically significant decrease in STT-1 and PS values (P < 0.005), and a statistically significant increase in IOP (P < 0.05). All these variations remained in the range of normal values. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol administered intramuscularly at 0.2 mg/kg provided a degree of sedation allowing eye examination, but was found to interfere with STT-1, PS, and IOP values among the diagnostic tests studied. However, these values remained within normal limits.

Association between objective signs and subjective symptoms of dry eye disease in patients with systemic sclerosis.

The aim of this study was to evaluate the association between clinical signs and symptoms of dry eye disease (DED) in patients with systemic sclerosis (SSc). This cross-sectional observational study included 19 SSc patients and 19 normal subjects with no ocular symptoms or ocular surface disorders. Clinical parameters included tear film break-up time (tBUT), Schirmer I, lissamine green (LG) dye, and tear film osmolarity tests, tear production, and tear secretion flow. For assessment of the dry eye symptoms, the Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients. The following mean values were found in SSc patients: OSDI 33.6 ± 19.86; osmolarity of the tear fluid 310.8 mOsmol/l ± 14.47; tBUT time 5.158 ± 2.328 s; Schirmer I test 5.395 mm/5 min; LG grading score 2.026 ± 0.8893; collected tear fluid volume 6.397 ± 2.761 µl. The calculated average tear velocity was 4.654 ± 1.963 µl/min. A significant correlation was found between the OSDI as a subjective parameter and disease duration. Early recognition of dry eye symptoms, a possible extra-intestinal manifestation of SSc, should be included in the check up of the disease to reduce ocular complications. The objective tear functional tests were strongly influenced by individual factors like age and disease duration.

Calcium-sensing receptor (CaSR) modulates ocular surface chloride transport and its inhibition promotes ocular surface hydration.

PURPOSE: Ocular surface hydration is critical for eye health and its impairment can lead to dry eye disease. Extracellular calcium-sensing receptor (CaSR) is regulator of ion transport in epithelial cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. CFTR is also a major ion channel in ocular surface epithelia, however the roles of CaSR in ocular surface are not well studied. This study aims to investigate expression and functional roles of CaSR in ocular surface. METHODS: CaSR immunostaining was performed in mouse and human cornea and conjunctiva. Ocular surface potential difference (OSPD) and tear fluid volume measurements were performed in mice with topically applied cinacalcet (CaSR activator) and NPS-2143 (CaSR inhibitor). RESULTS: CaSR is expressed in corneal and conjunctival epithelia of mice and humans. Topically administered CaSR activator cinacalcet inhibits cAMP agonist forskolin-induced Cl- secretion and CFTR activity up to 90 %. CaSR inhibitor NPS-2143 stimulates CFTR-mediated Cl- secretion in mouse ocular surface, after which cAMP agonist forskolin had minimal additional secretory effects. Single dose NPS-2143 treatment (as an eye drop) increases tear fluid volume in mice by ∼60 % compared to vehicle treatment. NPS-2143 effect on tear volume lasts at least 8 h after single dose. CONCLUSIONS: CaSR is a key regulator of ocular surface ion transport and CaSR inhibition promotes Cl- and tear secretion in the ocular surface. If they are found to be effective in in dry eye models, CaSR inhibitors (currently in clinical development) can potentially be repurposed as novel prosecretory treatments for dry eye disease.

A New Immortalized Human Lacrimal Gland Cell Line.

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

A PEDF peptide mimetic effectively relieves dry eye in a diabetic murine model by restoring corneal nerve, barrier, and lacrimal gland function.

PURPOSE: The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using streptozotocin. METHODS: Mice were treated topically for 3-6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury were measured using Cochet-Bonnet esthesiometer, phenol red cotton thread wetting, fluorescein sodium staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the lacrimal glands were measured. RESULTS: Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion and increased corneal epithelium injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1ß and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide treatment. CONCLUSION: The study demonstrates that topical application of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.

Symptoms and signs of dry eye in children with Graves' ophthalmopathy.

PURPOSE: The purpose of this study is to evaluate the tear secretion and ocular surface properties in children with Graves' ophthalmopathy (GO) and to compare the results with those of healthy children. METHODS: This was a cross-sectional study. Forty-three patients with GO (Group 1) and 41 healthy children without any ocular and/or systemic disorder (Group 2) were examined clinically and underwent tests for dry eye. We performed analyses including the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test under topical anesthesia (<5 mm was abnormal), slit-lamp biomicroscopy (corneal fluorescein staining and tear breakup time (TBUT) under blue-light illumination), and fundoscopic evaluation. RESULTS: Dry eye symptoms and the mean OSDI score were significantly (P < 0.02) higher (15.6 ± 18.7) in patients with GO compared with controls (5.67 ± 3.6). The mean Schirmer's (basal tear secretion) tests value was significantly reduced in Group 1 (5.25 ± 3.1 mm) compared with Group 2 (17.1 ± 5.2), respectively. The difference was statistically significant (p < 0.005), suggesting inadequate tear production. The mean tear film breakup time in children was lower in patients with GO (8.3 ± 3.42 s,) compared with controls (13.2 ± 4.74 s), (P < 0.001) suggesting an unstable tear film. Decrease of corneal sensitivity (23.3%) was noted in patients with GO compared with controls. GO patients showed a significant increase of the frequency of corneal fluorescein staining (6.9%) in patients with GO compared with controls. CONCLUSION: Patients with GO had a statistically significant higher incidence of dry eye symptoms and the increase of OSDI score. Significantly lower Schirmer's and TBUT tests results were seen in the study group when compared with the controls. These findings may indicate a tendency for dry eye in pediatric GO patients.

Blueberry Leaf Extract Prevents Lacrimal Hyposecretion in Sjögren's Syndrome-like Model of Non-obese Diabetic Mice.

BACKGROUND/AIM: This study evaluated the effect of blueberry leaf hot water extract (BLEx) on Sjögren's syndrome (SS)-like lacrimal hyposecretion in male non-obese diabetic (NOD) mice. MATERIALS AND METHODS: NOD or BALB/c mice were fed 1% BLEx or control (AIN-93G) for 2 weeks from the age of 4 to 6 weeks. Pilocarpine-induced tear volume was measured using a phenol red-impregnated thread. The lacrimal glands were evaluated histologically by H&E staining. The IL-1ß and TNF-α levels in the lacrimal gland tissue were measured by ELISA. The mRNA expression levels of secretion-related proteins were measured by real-time PCR. LC3 I/II and arginase 1 expression levels were measured by western blot. RESULTS: After feeding with BLEx, pilocarpine-induced tear secretion in NOD mice was increased. In contrast, the mRNA expression levels of the cholinergic muscarinic M3 receptor, aquaporin 5, and ion channels related to lacrimal secretion were not changed by BLEx administration. In addition, the protein expression of arginase 1, which was recently reported to be involved in tear hyposecretion in NOD mice, was also not improved by BLEx administration. Although infiltration in the lacrimal gland of NOD mice was not decreased, the levels of TNF-α and the autophagy-related protein LC3 were significantly suppressed by BLEx treatment. CONCLUSION: BLEx treatment may ameliorate lacrimal hyposecretion in NOD mice by delaying the progression of autoimmune disease by suppressing autophagy in lacrimal glands.

Blueberry Stem Extract Prevents Lacrimal Hyposecretion in Non-obese Diabetic Mice via Activation of AMPK.

BACKGROUND/AIM: Tears secreted from the lacrimal gland are essential for preserving the ocular surface. Thus, dysfunction of the lacrimal gland in Sjögren's syndrome (SS) can lead to dry eye, resulting in a reduced quality of life. We previously reported that blueberry 'leaf' water extract prevents lacrimal hyposecretion in male non-obese diabetic (NOD) mice in a SS-like model. In this study, we investigated the effect of blueberry 'stem' water extract (BStEx) on lacrimal hyposecretion in NOD mice. MATERIALS AND METHODS: Male NOD mice were fed 1% BStEx or control (AIN-93G) for 2, 4, or 6 weeks from 4 weeks of age. Pilocarpine-induced tear secretion was measured using a phenol red-impregnated thread. The lacrimal glands were histologically evaluated by HE staining. Inflammatory cytokine levels in the lacrimal glands were measured using ELISA. Immunostaining was performed to examine aquaporin 5 (AQP5) localization. The expression levels of autophagy-related proteins, AQP5, and phosphorylated AMPK were measured using western blotting. RESULTS: After feeding BStEx to mice for 4 or 6 weeks, tear volume was observed to have increased in the BStEx group compared with that in the control group. There were no significant differences in inflammatory cell infiltration, autophagy-related protein expression, or the localization and expression of AQP5 in the lacrimal glands between the two groups. In contrast, AMPK phosphorylation increased in the BStEx group. CONCLUSION: BStEx prevented lacrimal hyposecretion in the SS-like model of male NOD mice, probably by opening tight junctions via the activation of AMPK in lacrimal acinar cells.

Lysine Demethylase 1B Promotes Tear Secretion Disorder in Sjogren's Syndrome by Regulating the PAX6/CLU Axis.

The impacts of lysine demethylase 1B (KDM1B) have been probed in multiple diseases, but the effects of KDM1B on SS remained obscure. The study aimed to unravel the efficiency of KDM1B on SS progression via the paired box 6 (PAX6)/clusterin (CLU) axis. NODB10. H2b mice were selected to establish the SS model. KDM1B, Pax6, and CLU expression in SS mice was assessed. Adeno-associated viruses carrying KDM1B, Pax6, and CLU were injected into the SS mice to detect tear secretion, epithelium corneal fluorescein staining scores, and levels of specific markers of lacrimal gland epithelial cells, neurotransmitter receptors that induce secretion from the lacrimal gland, and genes encoding normal tear components. The relation among KDM1B, Pax6, and CLU was examined. The rescue experiments were conducted for verifying the interaction among KDM1B, Pax6, and CLU. KDM1B expression was elevated, while Pax6 and CLU levels were decreased in the lacrimal gland tissues of SS mouse models. KDM1B decrement and Pax6 augmentation improved tear secretion, reduced corneal fluorescein staining score, decreased levels of specific markers of lacrimal gland epithelial cells, and increased levels of neurotransmitter receptors that induce secretion from the lacrimal gland and genes encoding normal tear components. KDM1D suppressed Pax6 expression by mediating H3K4me2 demethylation. Pax6 promoted the expression of CLU at the transcriptional level by binding to the CLU promoter. Silencing of Pax6 or CLU could reverse the effects of KDM1B reduction on improving the tear secretion disorder of SS mice. Silencing KDM1B mitigates the tear secretion disorder of SS mice via modulating the Pax6/CLU axis.

Acupuncture for aqueous deficiency dry eye: a randomized controlled trial. / é’ˆåˆºæ²»ç–—æ°´æ¶²ç¼ºä¹åž‹å¹²çœ¼ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the clinical efficacy and safety of acupuncture and sodium hyaluronate eye drop in the treatment of aqueous deficiency dry eye. METHODS: A total of 60 patients (120 eyes) with aqueous deficiency dry eye were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 1 case dropped out). In the control group, sodium hyaluronate eye drop were used, one drop at a time, 4 times a day, for 14 consecutive days. In the observation group, acupuncture was applied at bilateral Shangjingming (Extra), Cuanzhu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5), and Tongziliao (GB 1) , once a day, treatment for 6 days with the interval of 1 day was required, for 14 consecutive days. The tear meniscus height (TMH), Schirmer Ⅰ test (SⅠT), ocular surface disease index (OSDI) score, non-invasive tear break-up time (NIBUT), and corneal fluorescein sodium staining (FLS) score were compared between the two groups before and after treatment, and the safety of the treatment of the two groups was observed. RESULTS: Compared with those before treatment, after treatment, TMH, SⅠT and NIBUT were increased (P<0.01, P<0.05), and FLS scores were decreased (P<0.01) in the two groups; the score of OSDI was reduced (P<0.01) in the observation group. After treatment, in the observation group, TMH and SⅠT were higher than those in the control group (P<0.01), and the score of OSDI was lower than that in the control group (P<0.01). No adverse reactions and adverse events were observed in the two groups. CONCLUSIONS: Acupuncture and sodium hyaluronate eye drop can both effectively treat aqueous deficiency dry eye, acupuncture has obvious advantages in improving TMH and basic tear secretion, and reducing the subjective symptoms of patients. Acupuncture for dry eye is safe.

Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects.

PURPOSE: To measure, the tear flow changes evoked in healthy subjects and dry eye disease (DED) patients by controlled sensory stimulation of the eye surface with i-Onion™, a new stimulation device. METHODS: Sensory corneal nerves were stimulated with an instrument (i-Onion™) that ejects puffs of CO2 gas (99.9%) at 200 ml·min-1 for 3s, delivered 5 mm from the cornea. Using Schirmer test strips, tear volumes were measured over 3 min in the cornea of one eye before (basal tear volume -BTV) and in the other eye after stimulation of the sensory nerves with CO2 (stimulated tear volume -STV). These measurements were obtained from a control group of adults of either sex (17 students aged 20-30 and 29 subjects without signs of dry eye aged 25-61), a cohort of DED patients (aged 34-75) that included 12 asymptomatic, suspected DED subjects (Schirmer <7 mm and/or TBUT <10s), and 30 Sjögren's syndrome (SS) patients. RESULTS: CO2 stimulation significantly increased the tear volume (BTV = 14.6 ± 1.0 mm, STV = 19.0 ± 1.1 mm: n = 46) in 78% of control subjects, reflecting a mean tear reserve volume (TRV = STV-BTV) of 4.4 ± 0.8 mm. Individual differences were wide, and while no increase in reflex tearing was evoked in 30% of subjects with a BTV >10 mm, the remaining 70% responded vigorously to stimulation, even those with a BTV >18 mm. Asymptomatic DED subjects displayed weaker responses to CO2 stimulation, with lower STVs. Both the BTV and STV of SS patients were low, significantly below those of the healthy controls. CONCLUSIONS: Measuring the rise in reflex tearing volume evoked by controlled corneal stimulation provides objective information about the tear glands' secretory capacity in health and disease.

Is dacryocystectomy effective in reducing epiphora?

Purpose: To study the efficacy of dacryocystectomy (DCT) in reducing epiphora in cases of primary acquired nasolacrimal duct obstruction. Methods: This was a prospective, nonrandomized, interventional study conducted over a period of 12 months. All cases who either opted or satisfied our criteria for DCT in primary acquired nasolacrimal duct obstruction (age above 70 years) were included in the study. Patients with secondary nasolacrimal duct obstruction and those undergoing revision surgeries were excluded. Patients were asked to report the percentage improvement in postoperative watering subjectively. Munk score and fluorescein dye disappearance test (FDDT) were recorded pre- and postoperatively. Wilcoxon signed ranked test was used for analysis. Results: Eighty-two eyes of 65 patients were included. Most of the patients (46, 70.8%) were females. The mean age was 68.46 ± 5.7 years (range: 60-85 years). The mean subjective improvement in watering was 86.8%. The P value for preoperative and postoperative difference in Munk score and FDDT score was highly significant (P = 0.00001). Conclusion: Apart from providing relief from ocular discharge, DCT also provides significant improvement in watering. Patients can be preoperatively counseled regarding chances of reduction in epiphora following surgery.

Quercetin improves lacrimal gland function through its anti-oxidant actions: Evidence from animal studies, and a pilot study in healthy human volunteers.

Anti-oxidant properties of polyphenols have been gaining medical attention as a preventive factor against aging and/or lifestyle diseases. In this study, we examined the anti-oxidant activity of quercetin improved tear function through its effects on the lacrimal gland in mice and humans. Six week-old diabetic mice, a model for decreased tear production, were fed for 12 weeks ad libitum with an experimental diet containing 0.5% quercetin. As a result, the tear volume was significantly improved compared to the control, despite no changes in body weight, food intake, lacrimal gland morphology or biochemical serum parameters. Moreover, significantly higher SOD-1 and SOD-2 protein levels were detected in the lacrimal glands of quercetin-treated mice by western blot. In addition, quercetin treatment of mouse corneal cell lines exposed to oxidative stress resulted in dose-dependent inhibition of ROS production and enhanced cell survival. Finally, we examined quercetin pharmacokinetics, specifically its presence in serum and tears subsequent to onion consumption in healthy volunteers, and found that the distribution of quercetin and its metabolite shifted from serum to tear following onion intake. An improvement in tear film stability also resulted following the intake by these healthy volunteers of a new, quercetin-rich onion cultivar ("Quergold") in powder form. These results suggested that quercetin improved tear function through its effects on the lacrimal gland in mice and humans.