Dry Eye Disorders Research Articles

Blink Rate, Incomplete Blinks and Computer Vision Syndrome

Computer vision syndrome (CVS), a highly prevalent condition, is frequently associated with dry eye disorders. Furthermore, a reduced blink rate has been observed during computer use. The present study examined whether post task ocular and visual symptoms are associated with either a decreased blink rate or a higher prevalence of incomplete blinks. An additional trial tested whether increasing the blink rate would reduce CVS symptoms. Subjects (N = 21) were required to perform a continuous 15-minute reading task on a desktop computer at a viewing distance of 50 cm. Subjects were videotaped during the task to determine their blink rate and amplitude. Immediately after the task, subjects completed a questionnaire regarding ocular symptoms experienced during the trial. In a second session, the blink rate was increased by means of an audible tone that sounded every 4 seconds, with subjects being instructed to blink on hearing the tone. The mean blink rate during the task without the audible tone was 11.6 blinks per minute (SD, 7.84). The percentage of blinks deemed incomplete for each subject ranged from 0.9 to 56.5%, with a mean of 16.1% (SD, 15.7). A significant positive correlation was observed between the total symptom score and the percentage of incomplete blinks during the task (p = 0.002). Furthermore, a significant negative correlation was noted between the blink score and symptoms (p = 0.035). Increasing the mean blink rate to 23.5 blinks per minute by means of the audible tone did not produce a significant change in the symptom score. Whereas CVS symptoms are associated with a reduced blink rate, the completeness of the blink may be equally significant. Because instructing a patient to increase his or her blink rate may be ineffective or impractical, actions to achieve complete corneal coverage during blinking may be more helpful in alleviating symptoms during computer operation.

Cosmetic Regional Conjunctivectomy With Postoperative Mitomycin C Application With or Without Bevacizumab Injection

To evaluate the complications of cosmetic wide conjunctivectomy and postoperative topical mitomycin C application with or without bevacizumab injection. Cross-sectional cohort study. Medical records of 1713 consecutive subjects who received cosmetic wide conjunctivectomy plus postoperative topical mitomycin C by a single surgeon at a single center with or without bevacizumab injection from November 2007 to May 2010 were reviewed. A telephone interview was conducted with 557 of the subjects who could be contacted and agreed to participate in the study. Complications, recurrences, and patient satisfaction were the main outcome measures. A total of 1713 consecutive patients underwent cosmetic wide conjunctivectomy to treat conjunctival hyperemia. Ocular diagnoses in the medical records at the time of surgery included hyperemia (8.8%), pterygium (14.0%), dry eye (3.5%), pinguecula (1.5%), and conjunctival disorder (23.3%). For the remaining 48.9% of subjects, the diagnosis was not mentioned, or the surgical procedure was for cosmetic purposes. Patients were followed for a mean of 10.9 months (range, 0-30.3 months). The overall complication rate was 82.9%, of which 55.6% were considered severe (fibrovascular conjunctival tissue proliferation, 43.8%; scleral thinning, 4.4%; scleral thinning with calcified plaques, 6.2%; intraocular pressure elevation, 13.1%; diplopia, 3.6%; and recurrence of hyperemic conjunctiva, 28.1%). Cosmetic wide conjunctivectomy plus postoperative topical mitomycin C with or without bevacizumab injection has a high rate of complications and reoperations.

Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders

BackgroundWomen, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and antiinflammatory properties of essential polyunsaturated fatty acids (EPUFAs).ObjectiveTo analyze whether a combined formulation of antioxidants and long-chain EPUFAs may improve the evolution of DEDs.MethodsWe used a prospective study to address the relationship between risk factors, clinical outcomes, and expression levels of inflammation and immune response (IIR) mediators in human reflex tear samples. Participants included: (1) patients diagnosed with nonsevere DEDs (DED group [DEDG]); and (2) healthy controls (control group [CG]). Participants were randomly assigned to homogeneous subgroups according to daily oral intake (+S) or not (−NS) of antioxidants and long-chain EPUFAs for 3 months. After an interview and a systematized ophthalmic examination, reflex tears were collected simultaneously from both eyes; samples were later subjected to a multiplexed particle-based flow cytometry assay. A specific set of IIR mediators was analyzed. All data were statistically processed through the SPSS 15.0 software program.ResultsSignificantly higher expressions of interleukin (IL)-1β, IL6, and IL10 and significantly lower vascular endothelial growth factor expressions were found in the DEDG as compared to the CG. In the DEDG, significant negative correlations were detected between the Schirmer test and IL-1β, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1β, IL6, and IL10 in tears were significantly lower in the DEDG+S versus the DEDG−NS and in the CG+S versus the CG−NS. Subjective symptoms of dry eye significantly improved in the DEDG+S versus the DEDG−NS.ConclusionIIR mediators showed different expression patterns in DED patients, and these patterns changed in response to a combined formulation of antioxidant and EPUFAs supplementation. Our findings may be considered for future protocols integrating clinical/biochemical data to help manage DED patients.

Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids

BackgroundGlaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases.ObjectiveOur objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG).MethodsParticipants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (−NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0).ResultsComparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients.ConclusionInflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.

The interblink interval in normal and dry eye subjects

PurposeOur aim was to extend the concept of blink patterns from average interblink interval (IBI) to other aspects of the distribution of IBI. We hypothesized that this more comprehensive approach would better discriminate between normal and dry eye subjects.MethodsBlinks were captured over 10 minutes for ten normal and ten dry eye subjects while viewing a standardized televised documentary. Fifty-five blinks were analyzed for each of the 20 subjects. Means, standard deviations, and autocorrelation coefficients were calculated utilizing a single random effects model fit to all data points and a diagnostic model was subsequently fit to predict probability of a subject having dry eye based on these parameters.ResultsMean IBI was 5.97 seconds for normal versus 2.56 seconds for dry eye subjects (ratio: 2.33, P = 0.004). IBI variability was 1.56 times higher in normal subjects (P < 0.001), and the autocorrelation was 1.79 times higher in normal subjects (P = 0.044). With regard to the diagnostic power of these measures, mean IBI was the best dry eye versus normal classifier using receiver operating characteristics (0.85 area under curve (AUC)), followed by the standard deviation (0.75 AUC), and lastly, the autocorrelation (0.63 AUC). All three predictors combined had an AUC of 0.89. Based on this analysis, cutoffs of ≤3.05 seconds for median IBI, and ≤0.73 for the coefficient of variation were chosen to classify dry eye subjects.Conclusion(1) IBI was significantly shorter for dry eye patients performing a visual task compared to normals; (2) there was a greater variability of interblink intervals in normal subjects; and (3) these parameters were useful as diagnostic predictors of dry eye disease. The results of this pilot study merit investigation of IBI parameters on a larger scale study in subjects with dry eye and other ocular surface disorders.

Autologus serum in treatment of dry eye disorder:An evaluation

Dry eye syndrome is a common disorder of the tear film in which eye is unable to maintain a healthy layer of tears to coat it. Despite various conventional treatments such as ocular surface lubrication, artificial tears, protective glasses and punctal occlusion many patients continue to have signs and symptoms of dry eye. That’s why autologous serum eye drops have been indicated for the treatment of dry eye. Therefore, to evaluate the effectiveness of the autologous serum eye drops in dry eye disorder, a total of 34 eyes of 20 patients were included in this study, who used autologus serum eye drops along with artificial tears. Out of 20 patients, 16 were males and 4 were females with M: F ratio of 4:1. The mean age of the patients was 51.95 years. Evaluations of patients were done before and after treatment in follow up, by determining the subjective and objective scores which showed that after follow up of 2 months all the subjective and objective scores were reduced in 28 eyes but 6 eyes did not show any improvement at follow up of 2 months as they stopped the drops after one month of use because of discomfort.

Differential contribution of hypertonic electrolytes to corneal epithelial dysfunction

The surface of the eye is covered by a protective tear film consisting of an aqueous-mucus layer and a superficial lipid layer, which are vital for light refraction and protection of vision. The aqueous component of the tear film contains electrolytes and a large variety of proteins, peptides and glycoproteins secreted by the lacrimal and meibomian glands, and apical cells of the corneal and conjunctival epithelia (Ohashi, Y. et al., 2006; Ruiz-Ederra, J. et al., 2009). Maintenance of a precise osmotic gradient of electrolytes between the tear film and the ocular surface epithelia is of paramount importance in regulating cell function and homeostasis. An imbalance of electrolytes is a hallmark of many pathologies, including dry eye, a disease affecting between 6 and 43 million people in the United States alone (Gilbard, J.P., 1994; Pflugfelder, S.C., 2011).

Optimizing Refractive Outcomes in the Presence of Ocular Allergy—Toward a Comprehensive Approach to Ocular Surface Health

Seasonal and perennial allergic conjunctivitis are common conditions which, along with dry eye and other inflammatory disorders of the ocular surface, may present an underlying management challenge in refractive surgery. Optimizing the condition and health of the ocular surface is essential in contact lens wearers, refractive surgical candidates, and post-surgical patients alike. Achieving an optimal ocular surface demands a comprehensive understanding of ocular allergy and related ocular surface conditions, as well as a proactive therapeutic approach. Although ocular allergy has often been implicated in contact lens intolerance, research has now begun to document the potential impact of allergic conjunctivitis on refractive surgical outcomes as well. Additional studies are needed to understand the relationship of allergic conjunctivitis to concomitant ocular surface disease and long-term ocular surface health. Further investigation of the potential benefit of better management of chronic episodic ocular surface inflammation, particularly in refractive surgery, will assist with the identification of optimal therapies.

High Resolution Microscopy of the Lipid Layer of the Tear Film

Tear film evaporation is controlled by the lipid layer and is an important factor in dry eye conditions. Because the barrier to evaporation depends on the structure of the lipid layer, a high resolution microscope has been constructed to study the lipid layer in dry and in normal eyes. The microscope incorporates the following features. First, a long working distance microscope objective is used with a high numerical aperture and resolution. Second, because such a high resolution objective has limited depth of focus, 2000 images are recorded with a video camera over a 20-sec period, with the expectation that some images will be in focus. Third, illumination is from a stroboscopic light source having a brief flash duration, to avoid blurring from movement of the lipid layer. Fourth, the image is in focus when the edge of the image is sharp – this feature is used to select images in good focus. Fifth, an aid is included to help align the cornea at normal incidence to the axis of the objective so that the whole lipid image can be in focus. High resolution microscopy has the potential to elucidate several characteristics of the normal and abnormal lipid layer, including different objects and backgrounds, changes in the blink cycle, stability and fluidity, dewetting, gel-like properties and possible relation to lipid domains. It is expected that high resolution microscopy of the lipid layer will provide information about the mechanisms of dry eye disorders. Illustrative results are presented, derived from over 10,000 images from 375 subjects.

Introductory overview of purinergic signalling

Purinergic neurotransmission was proposed in 1972 following identification of adenosine 5'-triphosphate (ATP) as the transmitter in non-adrenergic, non-cholinergic inhibitory nerves in guinea-pig taenia coli. Subsequently ATP was identified as a co-transmitter in sympathetic, parasympathetic and most nerves in the peripheral and central nervous systems. ATP acts as a short-term signalling molecule in neurotransmission, neuromodulation and secretion and has long-term (trophic) roles in cell proliferation, differentiation and death in development and regeneration. Three subclasses of purine and pyrimidine receptors have been identified, P1 adenosine receptors (4 subtypes), P2X ionotropic nucleotide receptors (7 subtypes) and P2Y metabotropic receptors (8 subtypes). ATP is released physiologically by many cell types by mechanical deformation and, after release, ATP undergoes ectonucleotidase degradation. Purinergic receptors appeared early in evolution and have a widespread distribution on many non-neuronal cells and neurons. Purinergic signalling is involved in embryonic and stem cell development. There is a rapidly growing literature about the pathophysiology of purinergic signalling including therapeutic developments for diseases, including stroke, thrombosis, osteoporosis, kidney failure, bladder incontinence, cystic fibrosis, dry eye, cancer and brain disorders.

Molecular modeling study on potent and selective adenosine A 3 receptor agonists

Adenosine A 3 receptor (A 3AR) is involved in a variety of key physio-pathological processes and its agonists are potential therapeutic agents for the treatment of rheumatoid arthritis, dry eye disorders, asthma, as anti-inflammatory agents, and in cancer therapy. Recently reported MECA (5′- N-methylcarboxamidoadenosine) derivatives bearing a methyl group in N 6-position and an arylethynyl substituent in 2-position demonstrated to possess sub-nanomolar affinity and remarkable selectivity for the human A 3AR, behaving as full agonists of this receptor. In this study, we made an attempt to get a rationalization of the high affinities and selectivities of these molecules for the human A 3AR, by using adenosine receptor (AR) structural models based on the A 2AAR crystal structure and molecular docking analysis. Post-docking analysis allowed to evaluate the ability of modeling tools in predicting AA 3R affinity and in providing interpretation of compound substituents effect on the A 3AR affinity and selectivity.

Tolterodine extended release is well tolerated in older subjects

Objectives:To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB).Methods:This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8–12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65–74 (n = 1059) and ≥ 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms.Results:Discontinuation rates were slightly higher among subjects ≥ 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65–74 or ≥ 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment × age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65–74 years, 16%; ≥ 75 years, 15%). The occurrence of all other AEs was ≤ 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts.Conclusion:The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.

A Comparison of Vitamin A and Cyclosporine A 0.05% Eye Drops for Treatment of Dry Eye Syndrome

To compare the efficacy of vitamin A (retinyl palmitate) and cyclosporine A 0.05% eye drops in treating patients with dry eye disease. Prospective, randomized, controlled, parallel group study. A total of 150 patients with defined dry eye disease participated (50 in each treatment group). In 3 identical clinical trials, patients were treated twice daily with cyclosporine A 0.05%, or four times daily with retinyl palmitate 0.05%, or with neither cyclosporine or retinyl palmitate. Adjunctive treatment with preservative-free artificial tears was undertaken four times daily in all 3 groups. Corneal fluorescein staining results, Schirmer tear test (without anesthesia) results, tear film break-up time (BUT), dry eye symptom score, and impression cytologic analysis results were obtained before treatment and at the first, second, and third months after initiation of treatment. Both vitamin A eye drops and topical cyclosporine A 0.05% treatments led to significant improvement in blurred vision, tear film BUT, Schirmer I score results, and impression cytologic findings in patients with dry eye syndrome (P < .05) compared to the control group treated with preservative-free artificial tears alone. Both vitamin A eye drops and topical cyclosporine A 0.05% treatments are effective for the treatment of dry eye disorder.

OOKP ‐ the Singapore Experience

Abstract Purpose: The management of severe ocular surface diseases and end‐stage dry eye disorders such as Stevens Johnson syndrome, ocular cicatricial pemphigoid and chemical burns with conventional keratoplasty or keratolimbal allografting remains unsatisfactory. The Osteo‐Odonto Keratoprosthesis (OOKP) is a form of keratoprosthesis (artificial cornea) surgery designed to treat the most severe of these cases, and good outcomes with long‐term retention have been reported. We present the moderate‐term clinical results of Asian patients who have had this device implanted within our Singapore OOKP Program. Methods: OOKP surgery involves a radical two‐stage procedure – in stage 1, an autologous canine tooth is removed, modified to receive an optical PMMA cylinder, and implanted into the cheek. The entire ocular surface is denuded and replaced with a full thickness buccal mucosal graft. Stage 2 surgery, performed 2‐4 months later, involves retrieval of the tooth‐cylinder complex and implanting it into the cornea, after lifting of the buccal mucosal flap, corneal trephination, iris and lens removal and anterior vitrectomy. Concurrent glaucoma and vitreo‐retinal procedures may also be performed at either stage, if required. Indications for OOKP surgery include bilateral severe blindness, not amenable to keratoplasty or ocular surface transplantation or with previous failed attempts. Results: In February 2004, the Singapore National Eye Centre embarked on its OOKP program, in collaboration with the National Dental Centre. We have now performed OOKP surgery on 22 patients, with the longest follow‐up being 39 months. Of 16 patients with a mean of 19.1 months follow‐up (range 5‐39 months), no major keratoprosthesis‐related complications have occurred, with full anatomical stability and retention in all cases. 73.3% of patients attained at least 6/12 or better vision, while 90% attained 6/6 vision, and remaining patients have attained, and retained their best visual potential with the exception of one patient who lost vision unrelated to the KPro device (endophthalmitis following glaucoma surgery occurred 1 year after KPro surgery). Conclusions: OOKP surgery appears to be a highly promising procedure which has the potential to restore excellent vision to the most severe cases of end‐stage corneal disease, when all else has failed. Longer follow‐up of these cases is currently underway.

The role of oxidative stress and inflammation in the pathogenesis of dry eye

Dry eye is a multifactorial disease of the tears and the ocular surface that results in symptoms of discomfort,visual disturbance, and tear film instability with potential damage to the ocular surface. Increased osmolarityof the tear film and inflammation in the lacrimal system and ocular surface are important operational factors inthe genesis of some dry eye disorders. Mechanical abrasion secondary to tear deficiency may create aninflammatory environment where conjunctival epithelial cells and lymphocytes are stimulated to produce andsecrete various cytokines into the tear film. Elevated cytokine levels within the tear film, combined with reducedconcentrations of essential lacrimal-gland derived factors such as epidermal growth factor (EGF) andretinol create an environment in which terminal differentiation of the ocular surface epithelium is impaired.The histopathologic changes in the minor salivary gland and lacrimal gland biopsy are characterized by focaland/or diffuse lymphoid cell infiltrates and parenchymal destruction. The majority of cells in glandular biopsyspecimens are CD4+ cells with a small proportion of CD8+T-cells.Apoptosis of acinar cells and inflammatory cells are also key events in relation to development of dry eyes.We previously showed the presence of apoptosis of acinar cells, FasL expression in lacrimal glands and thatthe FasL expression highly correlated with glandular function especially in those patients without glandularenlargement. FasL expression of infiltrating lymphocytes were low in the lacrimal glands of patients with SSwith enlarged exocrine glands where the lacrimal gland function was well preserved even with massive lymphocyteinvasion. In other words, the infiltration of lymphocytes alone did not cause glandular dysfunction.Apoptosis of acinar cells may explain these differences. Oxidative stress is recently receiving the attention ofresearchers and clinicians as a possible mechanism in the development of dry eye disease. Tsubota et alhave shown, for the first time in the literature, increases in oxidative stress markers, changes in antioxidantrelatedgene expression, and discordance in differentiation capacity in corneal epithelia in dry eye conditions,suggesting a strong relationship between the accumulation of oxidative stress and the etiology of cornealepithelial alterations in blink-suppressed dry eye. The management of oxidative stress may provide a newapproach for the prevention and therapeutic treatment for dry eye syndromes. The increased awareness ofoxidative stress related to disease and the need to measure the delicate balance that exists between freeradicals and the systems in place to regulate them has given rise to a demand for new research tools.

Relationship of Symptomatology with Closed Chamber Infrared Thermometry and Humidity in Dry Eyes

To evaluate the relationship of symptoms of dry eye with closed chamber infrared thermometry and humidity measurements. The authors studied 54 patients (108 eyes) with dry eye disorders of different grades of clinical severity (mean age 35.75+/-14.37 years), 31 cases (62 eyes) with normal eyes (mean age 33.68+/-14.42 years), and 10 cases (20 eyes) with epidemic conjunctivitis (mean age 33.68+/-14.42 years). The symptoms and the clinical tests (Schirmer-1 test, fluorescein tear break up time, Lissamine green stain; closed chamber infrared thermometry and humidity) were used to establish the diagnosis of dry eyes. The closed chamber humidity difference was used to classify the groups of dry eye. The authors noted no temperature difference from closed to open eye position in dry eyes as compared to 0.10 +/- 0.00 degrees C difference in normal eyes and epidemic conjunctivitis. Four groups of cases were identified by difference in values of humidity: Group 1 = <0.9 relative humidity (RH)% to 1 RH%; Group 2 = >1 RH% to 1.5 RH%; Group 3 = >1.5 RH% to 2 RH %; and Group 4 = >2 RH%. The symptomatology was measured in the eyes using Oxford scale (0-4) and correlated with the humidity groups. The grading of symptoms with the humidity showed a statistically significant relationship (p<0.0001) in each group. The severity of the symptoms showed an increase in frequency and severity from Group 1 to Group 4, which was statistically significant (p<0.0001). The mean sum total of global symptomatology score was statistically significant (p<0.0001): 3.43 +/- 0.31 in Group 1, 4.65+/-0.42 in Group 2, 8.56 +/- 0.78 in Group 3, and 13.35+/-1.21 in Group 4. However, total symptomatology score in epidemic conjunctivitis did not show a statistically significant value (p=0.20). The closed chamber humidity and thermometry measurements showed statistical correlation in all four groups of dry eyes to total mean symptomatology score (p<0.001) and showed an increase in value with increasing severity of symptoms. However, all individual symptoms fail to show any conclusive relationship.

Aquaporin-Dependent Water Permeation at the Mouse Ocular Surface: In Vivo Microfluorimetric Measurements in Cornea and Conjunctiva

Fluorescence methods were developed to quantify membrane and tissue water permeabilities at the ocular surface and to compare water transport in wild-type mice versus transgenic mice lacking each of the water channels, aquaporin (AQP)-1, -3, and -5, normally expressed in cornea or conjunctiva. Membrane water permeabilities (P(f)(mem)) of calcein-stained surface epithelial cells were measured from the kinetics of fluorescence quenching in response to rapid (<0.2 seconds) changes in extraocular fluid osmolarity. Tissue water permeabilities (P(f)(tiss)) across intact cornea and conjunctiva--the relevant parameters describing water movement into the hyperosmolar tear film in vivo--were determined by a dye-dilution method from the fluorescence of Texas red-dextran in an anisosmolar solution in a microchamber at the ocular surface. Osmotic equilibration occurred with an exponential time constant (tau) of 1.3 +/- 0.2 seconds (P(f)(mem) = 0.045 cm/s) in calcein-loaded corneal epithelial cells of wild-type mice, slowing 2.1 +/- 0.4-fold in AQP5-deficient mice; tau was 2.4 +/- 0.1 seconds in conjunctiva (P(f)(mem) = 0.025 cm/s), slowing 3.6 +/- 0.7-fold in AQP3-deficient mice. In dye-dilution experiments, P(f)(tiss) of cornea was 0.0017 cm/s and decreased by greater than fivefold in AQP5-deficient mice. P(f)(tiss) in AQP5-null mice was restored to 0.0015 cm/s after removal of the epithelium. P(f)(tiss) of conjunctiva was 0.0011 cm/s and was not sensitive to AQP3 deletion. These results define for the first time the water-transporting properties of the two principal ocular surface barriers in vivo. The permeability data were incorporated into a mathematical model of tear film osmolarity, providing insights into the pathophysiology of dry eye disorders.

What is dry eye and what does it mean to the contact lens wearer?

To define dry eye disease and describe the evolution of our understanding of the clinical expression and pathophysiology of dry eye. To relate tear function to contact lens wear and review the problems dry eye causes with contact lens tolerance and performance. Review of literature. The rudimentary definition of dry eye as a lack of tears is expanded through an increased understanding of the clinical presentations of dry eye. The classification of dry eye is historically reviewed. The pathophysiology is related to the evolution of therapy for dry eye disorders. The function of the tear film is related to contact lens wear and the problems induced by dry eye correlated with contact lens intolerance. The tear film is critical to successful contact lens wear. Disturbances of the quantity or quality of the tear film, whether because of aqueous deficiency or evaporative tear problems, results in intolerance of contact lens wear and damage to the ocular surface.

Shear-induced ATP release by cultured rabbit corneal epithelial cells.

The corneal epithelium is a barrier against the influx of fluid, solutes and pathogens from tear film into stroma. When this barrier is breached, corneal hydration control is compromised and susceptibility to pathogens increases significantly.1–3 Recent clinical investigations have shown the barrier property, expressed as permeability to fluorescein, is altered upon extended wear of contact lenses4,5 and in patients having dry eye disorder.6–8 Although the mechanism responsible for the alteration is unclear, it is well accepted that certain characteristics of the pre-corneal tear film such as thickness and rate of replenishment are affected in dry eye9,10 and contact lens wear situations.11,12 This observation may suggest a common mechanism involving the tear film plays a role in contact lens- and dry eye-induced loss of barrier property in the corneal epithelium. Given the principal role of the tear film as a lubricant for eyelids and contact lens motion relative to ocular surface epithelia, it is important to investigate how corneal and conjunctival epithelia respond to physical forces.

Effects of 15(S)-HETE on human conjunctival mucin secretion.

The pre-ocular tear film consists of an inner mucus layer that coats the epithelial surface, a middle aqueous layer containing soluble mucins and other proteins and an outermost lipid layer.1 Deficits in tear film mucins have been associated with several dry eye disorders,2–6suggesting that ocular mucin secretogogues may have therapeutic benefit for treatment of dry eye. Current evidence suggests that ocular surface epithelia express a diverse array of mucins, including MUC1, MUC2, MUC4, MUC5AC and MUC7.7–9 However, the physiological functions of individual tear film mucins remain largely unexplored.KeywordsOcular SurfaceLacrimal GlandNeurogenic InflammationVisual AuraKeratoconjunctivitis SiccaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.