Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye.
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Altered corneal epithelial barrier function is the cause for ocular irritation and visual morbidity in dry eye disease. Increased matrix metalloproteinase (MMP)-9 activity has been observed in the tear fluid of dry eye patients. To determine the pathogenic role of MMP-9 in the corneal epithelial disease of dry eye, the effects of experimentally induced dry eye on corneal epithelial morphology and barrier function were compared in MMP-9 knockout mice and their wild-type littermates. Dry eye was created through cholinergic blockade and exposure to a desiccating environment. The tear fluid MMP-9 concentration increased in response to dryness in wild-type mice. Corneal epithelial permeability to three different-sized molecules increased in dry eye wild-type mice, but not in MMP-9 knockout mice. Topical administration of active MMP-9 to dry eye MMP-9 knockout mice significantly increased corneal epithelial permeability. Compared to MMP-9 knockout mice, wild-type mice showed greater desquamation of differentiated apical corneal epithelial cells that expressed the tight junction protein occludin in response to dryness. This was accompanied by an increase in lower sized (50 kd) occludin in the corneal epithelia of wild-type mice. These findings could be replicated in cultured human corneal epithelial cells that were treated with active MMP-9. These studies indicate that increased MMP-9 activity on the ocular surface in response to dryness disrupts corneal epithelial barrier function. This appears to be because of accelerated loss of tight junction bearing superficial corneal epithelial cells, perhaps by proteolytic cleavage of occludin. (+info)
Case-controlled clinical and histopathological study of conjunctivochalasis.
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BACKGROUND/AIMS: Conjunctivochalasis, a secondary cause of the watery eye, is frequently seen in the older age group as an elevation of the bulbar conjunctiva lying along the lateral or central lower lid margin. A prospective, interventional, case-controlled clinical and histopathological study was conducted. The relevant features of 18 patients (29 eyes) who had their conjunctivochalasis resected as part of the surgical management of their watery eye syndrome were examined. In the control group, tissue was obtained from an age matched series of 24 normal subjects undergoing routine cataract surgery. METHODS: 24 controls (24 specimens) and 18 patients (29 specimens) had conjunctival strip biopsies, taken from the usual lid margin level bulbar conjunctiva in line with the inferior limbus (controls), and the clinically apparent conjunctivochalasis (patients). These were submitted for histological study. RESULTS: 23 of 24 control sections demonstrated normal conjunctival variation. Four of 29 patient specimens demonstrated a chronic non-granulomatous conjunctivitis, while three eyes of the patient group (two patients) demonstrated features of elastosis. Of the four patients who had the inflammatory infiltrates, three had functional nasolacrimal duct obstructions (FNLDOs) and one had a primary acquired nasolacrimal duct obstruction (PANDO). Of the two patients who had elastosis, one had an FNLDO and the other had normal lacrimal drainage and was Jones 1 positive. CONCLUSION: Six of 18 patients--that is, seven of 29 specimens of conjunctivochalasis demonstrated signs of elastosis or of chronic non-granulomatous inflammation. Clinically, patients had a spectrum of aetiologies of their watery eye syndrome. (+info)
SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye.
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PURPOSE: Protein and peptides in tears play an important role in ocular surface diseases. In previous studies, changes have been demonstrated in the electrophoretic protein profiles of patients with dry eye. The purpose of this work was to determine the usefulness of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip Array (Ciphergen Biosystems, Inc., Fremont, CA) technology for the automated analysis of proteins and peptides in tear fluid. METHODS: Patients with dry eye (DRY, n = 88) and healthy subjects (CTRL, n = 71) were examined. Their tear proteins were analyzed using SELDI-TOF-MS ProteinChip Arrays with three different chromatographic surfaces (CM10 cation exchange, Q10 anion exchange, and H50 reversed-phase) prepared by means of a laboratory liquid-handling robotic workstation. The data were analyzed by multivariate statistical techniques and artificial neural networks, and the most important biomarkers were purified and identified by tandem MS. RESULTS: Complex patterns of tear proteins and peptides were detected. The different chromatographic surfaces revealed the selective enrichment of proteins such as lipocalin and lysozyme. Discriminant analysis demonstrated highly significant changes in the protein profiles in patients with dry eye (P < 0.001). With a seven-peptide multimarker panel, an artificial neural network could differentiate between patients with dry eye and healthy individuals with a specificity and sensitivity of 90%. The identification of biomarkers revealed an increase of inflammatory markers in patients with dry eye and a decrease of some proteins that may have protective functions. CONCLUSIONS: The SELDI-TOF-MS technology seems to be ideally suitable for the mass screening of peptides and proteins in tears. This highly sensitive approach dramatically reduces the analysis time and provides protein profiles with great mass accuracy. Thus, it may become a very useful tool in the search for potential biomarkers for diagnosis and new therapeutics in ocular diseases such as dry eye. (+info)
Tear film dynamics in floppy eyelid syndrome.
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PURPOSE: Floppy eyelid syndrome (FES) presents nonspecific ocular surface irritation. The hypothesis for the current study was that one contributing factor is the abnormality in tear film dynamics. METHODS: Sixteen patients with FES were consecutively examined. Tear film dynamics were evaluated by kinetic tear interference images, infrared thermometry, water evaporation rate, tear break-up time, and fluorescein clearance test. Data showing evaporation rate and thermometry were compared with those of 10 normal subjects. RESULTS: There was a high correlation between the eye with the worse symptoms and the eyes with the more severe floppy lids (P < 0.01) and with ocular surface evaporation rate (P = 0.02). Except for one patient, all others showed abnormal tear film, with an average tear break-up time of 2.9 +/- 3.7 seconds. Kinetic analysis of tear interference images revealed that lipid spread in a vertical or mixed pattern in 18 eyes (75%) with a delayed spread time (P = 0.0007), indicating that most of the patients had lipid tear deficiency. The ocular skin temperature and water evaporation rate were higher in the FES group (P = 0.0003 and 0.026, respectively). Nearly all patients with FES showed eyelid hyperpigmentation. The ocular surface evaporation rate in the FES group was also higher than that of the normal subjects (P < 0.0001). Multiple regression analysis showed that a vertical pattern of lipid spread had a significant influence on ocular surface evaporation rate (P = 0.003). CONCLUSIONS: Tear film abnormality is prevalent in patients with FES and is characterized by lipid tear deficiency, leading to rapid tear evaporation. The FES lid skin is also characterized by high temperature, high water evaporation rate, and hyperpigmentation. Studies directed to investigating the linkage of lid changes and meibomian gland dysfunction may shed new lights on the pathogenesis of FES. (+info)
Association between symptoms and signs of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study.
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PURPOSE: To analyze the association between dry-eye symptoms and signs in an elderly Chinese population in Taipei, Taiwan. METHODS: The participants were those of the Shihpai Eye Study, a population-based survey of eye diseases in the elderly (> or =65 years) in Shihpai, Taipei, Taiwan. Of 2045 randomly selected noninstitutionalized residents, 1361 (66.6%) participated in the study. Dry-eye symptoms were evaluated with an interviewer-administered questionnaire. Dry-eye signs, including tear-film breakup time, Schirmer test result, score for fluorescein staining of the cornea, and meibomian gland dysfunction, were assessed. Correlations between symptoms and signs were analyzed. RESULTS: Of the participants, 33.7% (459/1361) were symptomatic, defined as reporting one or more symptoms often or all the time. A Schirmer result of < or =5 mm was the only sign associated with frequent symptoms (P = 0.028). Its sensitivity and specificity in detecting symptomatic subjects were 62.5% and 43.7%, respectively. The agreement between each sign was statistically significant, although weak, except that no correlation was found between the Schirmer result and meibomian gland anomalies. Of the symptomatic subjects, 85.4% (392/459) had either a low Schirmer result or a meibomian gland anomaly; 38.8% (178/459) of them were abnormal on both tests. CONCLUSIONS: The Schirmer test was shown to be incapable of detecting meibomian gland disease. However, a low Schirmer result was significantly associated with dry-eye symptoms in this elderly Chinese population. This result differs from that of previous reports of elderly white populations. Further studies are needed to determine whether this difference indicates racial diversity in the distribution and behavior of dry-eye diseases. (+info)
Dynamic changes in the tear film in dry eyes.
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PURPOSE: To examine the dynamics of the tear film in patients with dry eye by measuring the wavefront aberrations of the anterior surface of the film. METHODS: Anterior surface aberrations for a 7-mm pupil were determined in 13 patients with dry eye at 1-second time intervals, for 15 seconds after a blink. The aberrations were calculated from the elevations provided by corneal topography. All data were decomposed using Zernike polynomials. Total, spherical, and comalike aberrations terms were studied separately. Results were compared with those in normal eyes. Outcome measures included comparison with clinical tear breakup time measurements. RESULTS: The total root mean square (RMS) wavefront aberration in patients with dry eye passed through in a minimum of 2.9 +/- 0.4 seconds after a blink in comparison to the minimum at 6.1 +/- 0.5 seconds in normal patients. In both groups, the minimum in total aberration appeared to be associated with similar changes in comalike aberrations, rather than in spherical aberrations, which increased monotonically with time. The time at which minimum RMS aberration occurred correlated reasonably well with the measured tear breakup times. CONCLUSIONS: Measurements of the dynamic changes in the optical aberrations introduced by the anterior tear film surface give valuable insights into tear film changes and may provide a convenient objective method for the diagnosis of dry eye. (+info)
New perspectives in ocular surface disorders. An integrated approach for diagnosis and management.
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The cornea, conjuctiva and the limbus comprise the tissues at the ocular surface. All of them are covered by stratified, squamous, non-keratinizing epithelium and a stable tear film. The ocular surface health is ensured by intimate relationship between ocular surface epithelia and the preocular team film. There are two types of ocular surface failure. The first one is characterized by squamous metaplasia and loss of goblet cells and mucin expression. This is consistent with unstable tear film which is the hallmark of various dry-eye disorders. The second type of ocular surface failure is characterized by the replacement of the normal corneal epithelium in a process called limbal stem cell deficiency. It is essential to establish accurate diagnosis for appropriate management of complex ocular surface disorders. There has been considerable advancement in the understanding of the pathophysiology of ocular surface disease. Management has improved with introduction of the limbal stem cell concept and use of amniotic membrane transplantation. (+info)
Self-reported dry eye disease across refractive modalities.
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PURPOSE: To compare self-reported dry eye disease across contact lens wearers, spectacles wearers, and clinical emmetropes (i.e., those not requiring refractive correction). METHODS: The survey included two symptom questions (dryness and light sensitivity) that inquired about frequency and intensity at three times of day (morning, afternoon, and evening) and a self-perception question (i.e., Do you think you have dry eyes?). Dryness and light sensitivity scales were then calculated, summed, and scored, providing a dry eye classification. Logistic regression (binary and multinomial) and analysis of covariance were used to examine the relation between mode of refractive correction and dry eye status, frequency of symptoms, and diurnal change in symptom intensity. RESULTS: Overall, 893 surveys were completed, and the age-adjusted frequency of dry eye in the sample was 28.7%, with 3.5% of the sample reporting severe symptoms (at least grade 4 of a possible 5 for both symptoms). Contact lens wearers were most likely to report dry eye disease (52.3%), followed by spectacle wearers (23.9%) and clinical emmetropes (7.1%). Adjustment for age and gender showed that contact lens (adjusted odds ratio = 12.37, 95% confidence interval = 7.55-20.26) and spectacle wearers (adjusted odds ratio = 2.06, 95% confidence interval = 1.12-3.80) were more likely than emmetropes to report dry eye problems. After adjustment for age and gender, contact lens wearers were shown to be more likely to experience frequent symptoms and an increase in symptoms throughout the day (F = 51.4, P < 0.0001). CONCLUSIONS: The frequency of self-reported dry eye is high, especially in contact lens wearers. (+info)