Tear Flow Research Articles

The Effects of Menopause and Hormone Replacement Therapy on Quality and Quantity of Tear, Intraocular Pressure and Ocular Blood Flow

Objective: To evaluate the effects of menopause and hormone replacement therapy (HRT) on the quality and amount of tear, intraocular pressure (IOP) and retrobulbar blood flow velocities. Patients and Methods: Twenty women aged between 40 and 50 years, free of ocular and systemic diseases and planning to receive HRT were recruited as the study group. Twenty-four healthy, age-matched but still menstruating women were enrolled as controls. On the first day of study basal and reflex Schirmer test, tear break-up time and IOP measurements (at 08.00, 12.00 and 16.00 h) were performed for all groups. On the second day of the study, the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistivity index (RI) of the ophthalmic (OA), central retinal (CRA), nasal (NSPCA) and temporal short posterior ciliary (TSPCA) arteries were determined by color Doppler imaging. The menopausal group received HRT for 2 months, when all measurements were repeated for the 15 women who had received HRT on a daily basis. Results: The quality and amount of tear decreased (p < 0.01), IOP (p < 0.01) and RI of the CRA, TPCA and NPCA (p < 0.05) increased in postmenopausal women compared with the control group. After 2 months of HRT, the quality and amount of tear had increased (p < 0.001) and the IOP had decreased (p < 0.001). The PSV of the CRA and TSPCA had decreased (p < 0.05), as had the RI in the CRA (p < 0.001), NSPCA and TSPCA (p < 0.05). Conclusion: We conclude that age-induced changes on quality and amount of tear, IOP and retrobulbar blood flow are intensified by the menopause and that it may be possible to decrease the menopausal effects on these parameters by HRT.

Quantitative Lacrimal Scintigraphy After Dacryocystorhinostomy

To evaluate lacrimal drainage in patients who have undergone successful dacryocystorhinostomy using quantitative dacryoscintigraphy. This study included 72 eyes of 72 patients. There were 26 males and 46 females, with a mean age of 39.6 years (range, 8 to 67 years). The patients were subdivided into three groups. Group 1 consisted of 35 eyes with external dacryocystorhinostomy, group 2 consisted of 15 eyes with endoscopic dacryocystorhinostomy, and group 3 consisted of 22 eyes with conjunctival dacryocystorhinostomy with a Jones tube. There was no epiphora in patients and the lacrimal drainage systems were patent by irrigation. The other normal eyes of the patients were evaluated as controls. In groups 1 and 2, the mean T(1/2) values for the palpebral aperture were lower than those for normal eyes, and this difference was statistically significant (P < .01). In group 3, no significant difference was detected in the mean T(1/2) values for the palpebral aperture. Tear flow was slower in patients who had had external and endoscopic dacryocystorhinostomy, but conjunctival dacryocystorhinostomy did not affect T(1/2) values for the palpebral aperture.

Tear outflow. Impact of mucins and TFF-peptides

The epithelial lining of the lacrimal sac and the nasolacrimal duct consists of pseudo-stratified, columnar epithelia rich in goblet cells. Major secretory products of the epithelial cells are mucins together with TFF peptides. Expression and distribution of several mucins and TFF peptides in the human efferent tear ducts was investigated by means of reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. mRNAs for all the mucins investigated, MUC1, MUC2, MUC4, MUC5AC, MUC5B and MUC7, were detected in healthy human lacrimal sacs and nasolacrimal ducts. Both MUC5AC and MUC5B were detected in goblet cells forming intraepithelial mucous glands. MUC7 together with TFF3 occurred only in columnar epithelial cells of the efferent tear duct system. The mucin diversity of the efferent tear ducts could enhance tear transport and antimicrobial defense. The absence of some mucins in non-functioning although patent segments of the lacrimal passage, suggests that mucins ease tear flow through the efferent tear ducts because these conditions are associated with epiphora. Disorders in the balance of single mucins could be of importance with regard to dacryostenosis, dacryocystitis and dacryolith formation.

Group IIA phospholipase A 2 content in tears of patients having photorefractive keratectomy

Purpose: To study the effect of photorefractive keratectomy (PRK) on the concentration of group IIA phospholipase A 2 (GIIAPLA 2) in tears. Setting: Departments of Ophthalmology and Pathology, University of Turku, Turku, and Helsinki University Eye Hospital, Helsinki, Finland. Methods: Tear samples were collected from 25 eyes of 23 patients (mean age 32.3 years ± 8.6 [SD]) preoperatively and 2 and 7 days after PRK. The GIIAPLA 2 concentration in the tears was measured by time-resolved fluoroimmunoassay. Results: The GIIAPLA 2 concentration was significantly lower and the tear fluid flow rate significantly higher 2 days after PRK than preoperatively. At 7 days, the GIIAPLA 2 concentration and the tear fluid flow-corrected excretion of GIIAPLA 2 were significantly higher than preoperatively and at 2 days. The tear flow rate was also significantly higher than preoperatively. Conclusions: The GIIAPLA 2 content in tears decreased 2 days after PRK due to dilution of the GIIAPLA 2 content during hypersecretion of reflex tears. Photorefractive keratectomy caused an increase in the tear flow rate, GIIAPLA 2 concentration, and tear fluid flow-corrected excretion of GIIAPLA 2 in tears 7 days after surgery, enhancing the protection of tears against bacterial infections.

In vivo confocal microscopy for studying corneal diseases and conditions associated with corneal nerve damage.

Corneal sensory nerves are involved not only in corneal healing1–5 but they also participate in the reflex arc regulating tear fluid flow.6–8 Recent studies have also revealed that both stromal keratocytes and basal epithelial cells are innervated,9 an observation that further underlines the potential importance of neural input in corneal healing. In vivo confocal microscopy (CM) has proven to be a relatively reliable method for studying corneal nerves in clinical patient materials.10–13 The recovery of the normal morphology of the subbasal nerve bundles correlates with the restoration of corneal sensitivity.11 Unfortunately the Cochet-Bonnet esthesiometer seems to be relatively insensitive in detecting sensory alterations when compared with a non-contact gas esthesiometer.12 Nonhealing corneal ulcers are frequently associated with impaired corneal sensitivity and ocular surface pathology.14,15 Consequently, clinical tools that enable the direct evaluation of corneal innervation are needed. The current chapter is a review on our confocal microscopical findings on some post-surgical conditions such as PRK10 and LASIK,11,13,16,17 as well as some corneal diseases: familial amyloidosis type II/Meretoja disease,18 autosomal dominant cornea plana19, basement membrane dystrophy/recurrent erosion syndrome,20,21 diabetic neuropathy,20,22 herpes keratitis20 and Sjogren’s syndrome.

Group IIA phospholipase A2 content of basal, nonstimulated and reflex tears

Purpose. To determine the concentration of group IIA phospholipase A2 (GIIAPLA 2) in basal, nonstimulated and reflex tears of young normal subjects. Methods. The GIIAPLA 2 content of tears was measured in left eye of 16 healthy subjects (mean age 24.5 ± 2.2 years). Five samples were taken from each subject: nonstimulated sample; basal sample in a dark room after topical anesthesia; and reflex tear samples immediately on stimulation by bright light and breathing of the vapor of onions, and 1 and 3 minutes after the onset of tear flow. Results. The GIIAPLA 2 content of reflex tears was statistically significantly lower than the GIIAPLA 2 content of basal tears, whereas there was no statistically significant difference in the GIIAPLA 2 content between nonstimulated and basal tears. Conclusions. The current results indicate that the basal and nonstimulated tears are similar in their GIIAPLA 2 content, and that the GIIAPLA 2 content of tears decreases with stimulation, possibly due to dilution of GIIAPLA 2 content during reflectory hypersecretion of tears.

Human lacrimal drainage-associated lymphoid tissue (LDALT) belongs to the common mucosal immune system.

The lacrimal drainage system constitutes the part of the ocular adnexa where the tear flow drains after production in the lacrimal gland and subsequent to bathing the ocular surface. It is lined by a mucosa that continues that of the conjunctiva. The lacrimal drainage system begins at the two lacrimal puncta of the lid margin that lead via the lacrimal canaliculi into the cavernous lacrimal sac and via the nasolacrimal duct into the nose (Fig. 1).

Using osmolarity to diagnose dry eye: a compartmental hypothesis and review of our assumptions.

Two major forms of dry eye exist, aqueous-deficient (ADDE) and evaporative (EDE). 1 A major inflammatory component is also recognised. 1-2 The two forms have global features in common that identify them as dry eye, but do not specify cause. Of these, tear hyperosmolarity arises either as a result of evaporation in the presence of reduced tear flow, or excessive evaporation in the presence of a normal flow rate. Hyperosmolarity may contribute to inflammatory processes at the ocular surface by causing epithelial damage, possibly inducing cytokine release from epithelial cells. 5 Inflammation in dry eye is otherwise due to a complex process including autoimmune lacrimal gland and duct destruction, and release of inflammatory mediators from the gland and conjunctiva into tears. Tear instability results from a loss of stabilizing components of tears, such as mucin and lipocalin. Ocular surface damage may result from tear hyperosmolarity, proinflammatory mediators in the tears, and decreased lubrication between the lids and globe. These factors are probably responsible for many symptoms of dry eye..

The assessment of irritation using clinical methods and questionnaires.

Sensory irritant responses to chemical exposures are measured by a variety of methods; however, studies can be influenced from biases associated with study design and subject responses. This article reviews the different methods used to quantitate irritation. These methods primarily focus on eye and nasal mucosal irritation. Although methods to evaluate mouth, throat mucosal, and dermal irritation are also relevant, they are seldom used in actual practice. Measurements for eye irritation include tear film stability, epithelial damage, foam formation, blinking frequency, tear flow, inflammation, and hyperemia. Methods for detecting nasal mucosa irritation include measuring swelling of the nasal mucosa, peak airflows through the nose, acoustic rhinometry, and rhinostereometry, which measures thickness of the anterior nasal turbinate. Questionnaires are useful for defining a set of symptoms in an attempt to characterize dose-response relationships from controlled exposure studies or field studies, to compare rates of events in field studies, or to screen for disease. However, it is important to consider carefully the study design, goal of utilization, and constraints surrounding their application. Whichever method is used in medical surveillance or to evaluate effectiveness of industrial hygiene or engineering controls in preventing irritation effects from chemical exposure, the sensitivity, specificity, and predictive value of the irritation measurements are important factors in interpreting the results. This article reviews these various issues and offers some advice.

Human Tear Fluid PDGF-BB, TNF-α and TGF-β1 vs Corneal Haze and Regeneration of Corneal Epithelium and Subbasal Nerve Plexus after PRK

The aim was to determine the association of tear fluid cytokine levels and post-PRK corneal haze evaluated by in vivo confocal microscopy. In addition, the possible association between subbasal neural regeneration and haze formation, or epithelial regeneration were investigated. Twenty eyes of 20 patients (16 women and four men, age 30.7±7.5 years, range 21–48 years) underwent a myopic PRK. The spherical equivalent (SE) of the intended correction was −4.7±1.5D (range −2.75 to −9.00D). ELISA-methods were used to assess tear fluid concentrations of TGF-β1, PDGF-BB and TNF-α pre-operatively, and post-operatively on day 2 and at 3 months. Tear fluid flow in the collection capillary was recorded, and rates of cytokine release (=tear fluid flow-corrected concentrations) were calculated. In vivo confocal microscopy was performed at 3 months to evaluate the corneal morphology and to determine numerical haze estimate. There was wide interindividual variation between pre-operative and post-operative concentrations and rates of release of TGF-β1, PDGF-BB and TNF-α. Subepithelial haze was observed in all corneas and the mean haze estimate was 506±401U (100–1410U). However, no association was found between tear fluid cytokine levels and post-PRK haze. Regenerating subbasal nerve plexus was found in 18 out of 20 corneas; in two corneas it was absent or could not be visualized due to subepithelial haze. The density of the subbasal nerve fiber bundles had a positive correlation with the epithelial thickness (Pearson correlation, r=0.56, P=0.011), but not with the haze estimate or the thickness of the haze area. At 3 months post-PRK, haze could be observed in all patients. The results suggest that tear fluid cytokine analysis, as measured, may not be suitable for screening the potential candidates for haze formation. We did not find any correlation between haze and regeneration of subbasal nerve plexus, but we demonstrated that the regeneration of subbasal nerve plexus might have significant influence on regulation of epithelial healing.

Lacrimal gland fluid secretion and lymphocytic infiltration in the NZB/W mouse model of Sjögren’s syndrome

Purpose. The fluid secretory impairment of lacrimal and salivary glands in Sjögren’s syndrome (SS) is thought to be related to the extent of lymphocytic infiltration (LI) and subsequent loss of glandular tissue. In this study, we examine the correlation between the extent of tear flow reduction and the extent of LI of lacrimal glands in the NZB/W mouse, a model of SS. Methods. We stimulated tear production by topical application of carbachol onto the gland while fluid was collected from the lacrimal duct. The lacrimal glands were removed after fluid collection for histology. Results. Fluid secretion in response to carbachol was less in the majority of young NZB/W females compared to C57 control animals and none of the glands showed LI. Fluid secretion was also impaired in the majority of old NZB/W females, and the extent of LI was highly variable. Some of the old SW females also showed blunted fluid secretory responses and some degree of focal LI. Young SW females showed no LI and most animals exhibited normal flow responses. Analysis of paired flow and LI measurements showed no correlation between LI and flow impairment in any of the groups or in the pooled data. Carbachol-stimulated protein secretion from lacrimal gland slices in vitro were similar in young and old SW and NZB/W mice. Conclusions. These results suggest that LI alone is not sufficient to explain the secretory dysfunction in the NZB/W mouse model of Sjögren’s syndrome.

Effect of laser in situ keratomileusis on tear stability

Objective Patients frequently experience dry eye symptoms after laser in situ keratomileusis (LASIK). The mechanisms that lead to these changes are not well understood. The purpose of this study was to investigate the effect of LASIK on tear function. Design Prospective, comparative, nonrandomized interventional trial. Participants Fifty-eight consecutive patients (96 eyes) who underwent myopic LASIK treatment. Methods The prospective study involved 58 consecutive patients (96 eyes) who underwent sequential or bilateral LASIK for the correction of myopia. Dry eye symptoms, standardized Schirmer test values, basal tear secretion test, and tear break-up time were measured before surgery and 1 day, 1 week, and 1 month after surgery. Main outcome measures Schirmer test value, basal tear secretion value, and tear break-up time. Results Before surgery, 15.6% of patients (15/96) had dry eye symptoms. After surgery, 94.8% of patients (91/96), 85.4% of patients (82/96), and 59.4% of patients (57/96) experienced dry eye symptoms at 1 day, 1 week, and 1 month, respectively. Schirmer test value (13.32 ± 10.67 mm) increased at 1 day (14.48 ± 10.57 mm; P = 0.25) and subsequently decreased at 1 week (11.18 ± 9.81 mm; P = 0.05) and at 1 month (10.83 ± 10.02 mm; P = 0.03). Basal tear secretion test value (8.49 ± 8.48 mm) decreased at 1 day (6.80 ± 6.48 mm; P = 0.05), at 1 week (5.97 ± 6.88 mm; P = 0.005), and at 1 month (5.89 ± 6.24 mm; P = 0.007). Tear break-up time (5.32 ± 2.35 seconds) decreased 1 day (4.14 ± 1.90 seconds; P < 0.001) and 1 week (4.49 ± 1.70 seconds; P = 0.004) after surgery and recovered by 1 month after surgery (5.09 ± 3.03 seconds; P = 0.52). Poor preoperative tear functions with a Schirmer test value less than 10 mm was a significant risk factor (72% vs. 46%; relative risk, 1.58 [1.10–2.26]) for experiencing dry eye symptoms at 1 month after surgery. Conclusions Dry eye symptoms are common after myopic LASIK surgery. Laser in situ keratomileusis significantly altered the tear break-up time, Schirmer test values, and basal tear secretion. Patients with preexisting tear flow abnormality as demonstrated by Schirmer test values less than 10 mm are especially at risk of experiencing dry eye symptoms.

Endoscopic terminal dacryocystorhinostomy.

Traditional endoscopic dacryocystorhinostomy (DCR) involves creation of a lacrimal sac side hole that may close down in the presence of a partially patent lower lacrimal drainage system. Endoscopic terminal DCR is a modified DCR procedure designed to prevent this problem. From September 1996 to June 1999, 16 patients (17 sides) had endoscopic terminal DCR that involved resection of the lacrimal sac-duct junction to achieve total separation of the lacrimal sac from the nasolarcrimal duct and creation of a terminal DCR opening. Ten of the 17 DCRs were primary and 7 were revisions. The follow-up ranged from 3 to 36 months. There were two failures. One failure was due to canalicular obstruction and the other was due to prolapse of orbital fat hindering proper fashioning of the mucosal flap. The overall success rate was 88%. Instead of creating a side hole in the lacrimal sac as proposed by most endoscopic DCR studies, we advocate total diversion of tear flow by performing a terminal DCR opening that would further improve the success rate of endoscopic DCR, particularly in cases of idiopathic and partial obstruction.

Severe Destructive Autoimmune Lesions with Aging in Murine Sjögren's Syndrome through Fas-Mediated Apoptosis

When we evaluated the age-associated changes in autoimmune exocrinopathy in a NFS/sld murine model for primary Sjögren's syndrome (SS), severe destructive autoimmune lesions developed in the salivary and lacrimal glands in the aged mice, compared with those observed in the younger model. We detected a decreased secretion of saliva and tear flow in the aged group. A significant increase of TUNEL(+)-apoptotic epithelial duct cells in the salivary glands was detected in the aged SS animal model. A higher proportion of mouse salivary gland cells bearing Fas was found in the aged group, whereas no significant changes were seen on tissue-infiltrating CD4(+) T cells bearing FasL in the salivary glands from young and aged mice. We detected an increased cleavage product of organ-specific autoantigen, 120-kd alpha-fodrin, in the aged salivary gland tissues on immunoblotting, and an increase in serum autoantibody production against 120-kd alpha-fodrin by enzyme-linked immunosorbent assay. An increase in the proliferative response of splenic T cells against organ-specific autoantigen was observed, whereas nonspecific concanavalin A responsiveness was decreased in the aged mice. In addition, a decrease in Fas expression was found on splenic CD4(+) T cells in the aged mice, and anti-Fas mAb-stimulated apoptosis was down-regulated on CD4(+) T cells. These results indicate that age-associated dysregulation of CD4(+) T cells may play a crucial role on acceleration of organ-specific autoimmune lesions in a murine model for primary SS through Fas-mediated apoptosis.

Excessive tearing in infancy and early childhood

PREVIEWObstruction of tear outflow is a primary cause of excessive tearing in infants and young children. In this review of a common disorder, Dr Ballard explores the causes and anatomic and physiologic features of excessive tear flow in pediatric patients. Criteria for the differential diagnosis of overflow tearing are featured, and noninvasive and surgical techniques for the treatment of obstructions to nasolacrimal drainage are presented.

Tear production after unilateral removal of the main lacrimal gland in squirrel monkeys.

To study the effects of lacrimal gland removal on basal and reflex tear production and on the ocular surface in the squirrel monkey. Unilateral main lacrimal gland removal in 6 squirrel monkeys was followed by Schirmer testing, slit-lamp examination with fluorescein, and collection of basal and reflex (stimulated) tears for analysis of tear protein spectra between 0 and 20 kd, as well as histological evaluation. Schirmer test results showed an 80% decrease in basal tears and a 90% decrease in reflex tears during week 1, and a 32.2% and 33.3% decrease, respectively, at week 20 after surgery, compared with the contralateral control side. However, no gross abnormalities or fluorescein staining were seen in 5 of the 6 monkeys, and the conjunctival surfaces remained normal. The main and accessory lacrimal glands appeared to secrete similar types of proteins. No histological changes were seen in corneal, conjunctival, or eyelid tissues 20 weeks after surgery. Tears from accessory lacrimal glands were sufficient to maintain a stable tear layer on the cornea, suggesting that so-called basal tear flow is made up of fluid from both main and accessory lacrimal glands and that decreased tear production by the main lacrimal gland is not a causative factor in keratoconjunctivitis sicca. This study shows that total removal of the main lacrimal gland does not in itself lead to keratoconjunctivitis sicca. However, the nature of neural control of the accessory glands is not yet clear.

Tear secretion and tear film function in insulin dependent diabetics

BACKGROUNDDiabetic patients often complain of dry eye symptoms, such as burning and/or foreign body sensation. The aim of the present study was to investigate whether diabetes mellitus is correlated with...

Soluble Fas and Fas ligand in human tear fluid after photorefractive keratectomy

BACKGROUND/AIMSThe Fas-Fas ligand system is thought to be involved in stromal cell apoptosis after corneal wounding. The aim was to measure changes in human tear fluid levels of soluble Fas...

Preliminary tear film measurements of tolerant and non‐tolerant contact lens wearers

Background: The relationship between contact lens intolerance and tear stability, tear quantity, distribution and consistency has yet to be clearly established. In this study, we have examined the tear film of several tolerant and non‐tolerant soft contact lens wearers. We aimed to develop a number of clinical and biochemical techniques to establish a correlation between one or more factors leading to contact lens intolerance.Methods: Subjects were separated by their self‐described tolerance to contact lens wear. Five tolerant and five non‐tolerant subjects were chosen. A McMonnies symptomatology questionnaire was used to ascertain subject history, while non‐invasive tear break‐up time (TBUT) examined tear stability. Basal tear collection was performed using glass capillary tubes, the tear flow rate was measured and one dimensional gel electrophoresis used to analyse protein differences.Results: Non‐tolerant subjects experienced primary symptoms, such as dryness and grittiness, more often than tolerant subjects (p = 0.007). The TBUT of non‐tolerant lens wearers was also reduced (average of seven seconds) compared to tolerant lens wearers (p < 0.002). Tolerant lens wearers had a longer more stable tear film with an average TBUT of 20 seconds and this correlated with a fast tear flow rate (p < 0.04). Protein gel electrophoresis showed that some subjects who were non‐tolerant to lens wear had variations in their tear protein profiles compared to tolerant subjects.Conclusion: These preliminary results demonstrate that clinical and biochemical tear profiles can be used to differentiate subjects with good lens wear tolerance from those who may be non‐tolerant to lens wear.

Tumour necrosis factor alpha (TNFalpha) in tears of atopic patients after conjunctival allergen challenge.

Proinflammatory cytokines, such as TNFalpha are involved in the pathogenesis of allergic rhinitis and asthma. Our aim was to study the tear fluid TNFalpha levels in atopic patients before and after topical ocular allergen challenge. Thirteen patients were first challenged with topical allergen in the left eye and then dilution buffer in the right eye. Tear fluid samples were collected before the challenges and after 5, 30 and 60 min. Clinical symptoms were scored. Tear fluid TNFalpha concentrations were measured using a double-antibody radioimmunoassay. TNFalpha release rates were calculated using the tear fluid flow in the collection capillary as an estimate for the tear secretion rate. The mean baseline TNFalpha concentrations (ng/L) were 1310 (allergen-challenged eye) and 967 (control eye), and release rates (pg/min) 1.81 (allergen-challenged eye) and 1.39 (control eye), respectively. In the allergen-challenged eye, TNFalpha concentrations and release rates were 1479 and 4.30 (5 min), 1367 and 3.20 (30 min) and 1426 and 3.80 (60 min). In the control eye, TNFalpha concentrations and release rates were 746 and 0.67 (5 min), 1001 and 0.92 (30 min) and 1504 and 1.05 (60 min). The release rates of the allergen-challenged eye were significantly increased at all time points after the challenge when compared with the baseline or the control eye. Increased TNFalpha release rates suggest that this cytokine is an early mediator of allergy after conjunctival challenge.