lactoferrin and Dry-Eye-Syndromes

Lactoferrin (LF) is one of the major functional proteins in maintaining human health due to its antioxidant, antibacterial, antiviral, and anti-inflammatory activities. Abnormal levels of LF in the human body are related to some serious diseases, such as inflammatory bowel disease, Alzheimer's disease and dry eye disease. Recent studies indicate that LF can be used as a biomarker for diagnosis of these diseases. Many methods have been developed to detect the level of LF. In this review, the biofunctions of LF and its potential to work as a biomarker are introduced. In addition, the current methods of detecting lactoferrin have been presented and discussed. We hope that this review will inspire efforts in the development of new sensing systems for LF detection.

Topics: Alzheimer Disease; Animals; Biomarkers; Biosensing Techniques; Chromatography; Dry Eye Syndromes; Electrophoresis, Capillary; Feces; Humans; Immunoassay; Inflammatory Bowel Diseases; Lactoferrin; Predictive Value of Tests; Saliva; Tears

Lactoferrin is a naturally occurring iron-binding glycoprotein, produced and secreted by mucosal epithelial cells and neutrophils in various mammalian species, including humans. It is typically found in fluids like saliva, milk and tears, where it reaches the maximum concentration. Thanks to its unique anti-inflammatory, antioxidant and antimicrobial activities, topical application of lactoferrin plays a crucial role in the maintenance of a healthy ocular surface system. The present review aims to provide a comprehensive evaluation of the clinical applications of lactoferrin in ocular diseases. Besides the well-known antibacterial effect, novel interest has been rising towards its potential application in the field of dry eye and viral infections. A growing body of evidence supports the antimicrobial efficacy of lactoferrin, which is not limited to its iron-chelating properties but also depends on its capability to directly interact with pathogen particles while playing immunomodulatory effects. Nowadays, lactoferrin antiviral activity is of special interest, since lactoferrin-based eye drops could be adopted to treat/prevent the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which has conjunctivitis among its possible clinical manifestations. In the future, further data from randomized controlled studies are desirable to confirm the efficacy of lactoferrin in the wide range of ocular conditions where it can be used.

Topics: Animals; Anti-Infective Agents; Conjunctivitis; Coronavirus Infections; COVID-19; Dry Eye Syndromes; Humans; Lactoferrin; Pandemics; Pneumonia, Viral

To evaluate the potential of lactoferrin (Lf) as a diagnostic biomarker for ocular diseases using a meta-analytic approach.. All original studies reporting an estimate of the average Lf concentration in healthy subjects and those affected by ocular diseases were searched up to March 2020. The DerSimonian and Laird method was used to calculate the random effects pooled mean difference and the corresponding 95% confidence interval (CI) in Lf concentration between healthy subjects and those affected by dry eye (DE), Sjögren syndrome (SS), and diabetic retinopathy, separately. The presence of between-study heterogeneity was evaluated using the Cochran's Q test and the I2 index. Stratified analyses were performed to assess potential sources of heterogeneity and influence and cumulative analyses to evaluate the robustness of the results obtained. Publication bias was also evaluated using funnel plot and the Egger's test.. The pooled mean differences in Lf concentrations between healthy subjects and those with DE, Sjögren syndrome, and diabetic retinopathy were respectively 0.62 (95% CI, 0.35-0.89) for DE, 3.78 (95% CI, -6.64 to 14.17), and 0.19 (95% CI, -4.00 to 4.39). Regarding DE, the stratified analysis showed that geographical area (P value Q test < 0.0001) and sample size (P < 0.0005) were sources of heterogeneity. Moreover, no study substantially influenced the results obtained and the pooled mean difference became statistically significant after a sample size of 220. Publication bias may affect the results of DE.. The results of the current meta-analysis suggest that Lf level in tears is a good candidate as dry eye syndrome diagnostic biomarker.

Topics: Biomarkers; Diabetic Retinopathy; Dry Eye Syndromes; Eye Proteins; Humans; Lactoferrin; Sjogren's Syndrome; Tears

To elucidate the correlation between lactoferrin concentration in the tear film and signs and symptoms of severe dry eye disease (DED) using a novel microfluidic paper-based analytical device (μPAD) and enzyme-linked immunosorbent assay (ELISA).. Twenty-four patients were recruited at the Keio University Hospital. Using a novel μPAD, lactoferrin concentrations were measured in 4 patients with GVHD-related DED, 3 patients with other types of DED and 2 controls (Group A). For validation by ELISA, 22 patients (7 patients from Group A) comprising 9 patients with GVHD-related DED, 6 patients with other types of DED and 7 controls were examined (Group B). The link between lactoferrin concentration and clinical data about the severity of aqueous tear deficient DED was also investigated by both μPAD and ELISA.. The lactoferrin concentration in tear fluid of the DED patients was positively correlated between μPAD and ELISA (p = 0.006, r = 0.886). The tear fluid of the GVHD patients showed low or undetectable lactoferrin concentration. Analysis by ELISA demonstrated that lactoferrin concentrations in the tear film from the GVHD patients were significantly lower than those from the non-GVHD patients (p = 0.010576). ELISA revealed lactoferrin concentration correlated with the value of Schirmer test and tear film breakup time, whereas it was inversely correlated with OSDI, fluorescein and rose bengal scores.. The novel μPAD may pave the way for measuring lactoferrin concentration in tear fluid from DED patients. Our results suggested that lactoferrin concentration in tear fluid reflect the severity of DED.

Topics: Adult; Aged; Dry Eye Syndromes; Enzyme-Linked Immunosorbent Assay; Equipment Design; Female; Humans; Lactoferrin; Male; Middle Aged; Osmolar Concentration; Reproducibility of Results; Retrospective Studies; Tears

Dry eye is the most prominent pathology among those involving the ocular surface: a decrease of the aqueous (less frequent) or the lipid (more frequent) component of the tear film is the cause of the diminished stability of tears that is observed in this pathology. Dry eye shows a clear distribution linked to both sex (being more frequent among women) and age (increasing with aging). Therefore, specific treatments taking into account the etiology of the disease would be desired. The role of lactoferrin and its functional mimetic lactobionic acid are reported here as a possible remedy for age-related dry eye.

Topics: Disaccharides; Dry Eye Syndromes; Humans; Lactoferrin; Tears

This study compared the changes in tear inflammatory cytokine levels after intense pulsed light (IPL) combined with meibomian gland expression (MGX) (IPL group) and instant warm compresses combined with MGX (physiotherapy group) as treatments for meibomian gland dysfunction (MGD)-related dry eye disease (DED) to explore their similarities and differences in therapeutic mechanisms.. At the last measurement, a significant decrease was observed in all tear cytokines for both IPL and physiotherapy groups compared with baseline. The IPL group showed greater reductions in IL-6, IL-6R, IL-1β, IL-13, and CCL11/Eotaxin than the physiotherapy group. TNF-α, CXCL8/IL-8, CXCL10/IP-10, IL-10, EGF, IL-1β, IFN-γ, and Lipocalin-2/NGAL levels continued to decrease with treatment time. Important interactions were found in the changes of IL-6 and IL-13 levels, where the levels first decreased and then slightly increased in the physiotherapy group after treatment, while they continued to decrease in the IPL group.. The mechanisms of IPL and physiotherapy in treating MGD-related DED were both associated with reducing inflammation, and the superiority of IPL could be attributed to its better inhibitory effect on inflammatory cytokines like IL-6. In addition, several cytokines were on a downward trend during treatment, suggesting that the vicious cycle of DED was suppressed.

Topics: Chemokine CXCL10; Cytokines; Dry Eye Syndromes; Epidermal Growth Factor; Fas Ligand Protein; Humans; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-17; Interleukin-6; Interleukin-8; Lactoferrin; Lipocalin-2; Matrix Metalloproteinase 9; Meibomian Gland Dysfunction; Meibomian Glands; Tumor Necrosis Factor-alpha

To examine the effect of a combined dietary supplement containing fish oil, lactoferrin, zinc, vitamin C, lutein, vitamin E, γ-aminobutanoic acid, and Enterococcus faecium WB2000 on dry eye.. A preliminary study in a rat model and a prospective, randomized, double-blind, placebo-controlled study in humans were conducted. Forty Japanese volunteers aged 22 to 59 years were randomized into combined dietary supplement (2 capsules/day; 20 participants) and placebo (vehicle; 19 participants) groups and treated once daily for 8 weeks. Rats received the combined dietary supplement components (10 or 50 mg/kg orally) or vehicle (2% DMSO), and dry eye was mechanically induced for 2 days. Tear production was measured in rats after dry eye was induced. Humans were assessed at baseline and weeks 4 and 8 post-supplementation based on keratoconjunctival epithelial damage; fluorescein tear film breakup time; tear production; biochemical data; information regarding subjective dry eye symptoms by answering a questionnaire; and information regarding adverse events via medical interviews.. Supplementation dose-dependently mitigated the decrease in tear production in rats. Among subjects with confirmed dry eye, clinical symptoms improved at weeks 4 and 8 more significantly in the supplementation group than in the placebo group (P<.05). The rate of increase in the Schirmer value was greater in the supplementation group. No adverse events occurred.. Supplementation improved objective and subjective dry eye symptoms.

Topics: Adult; Animals; Dietary Supplements; Double-Blind Method; Dry Eye Syndromes; Enterococcus faecium; Fish Oils; Humans; Lactoferrin; Middle Aged; Prospective Studies; Rats; Tears; Young Adult

To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile.. 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits.. In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses.. In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile.. CTRI/2013/07/003802.

Topics: Administration, Topical; Adult; Aged; Conjunctiva; Double-Blind Method; Dry Eye Syndromes; Electrophoresis, Polyacrylamide Gel; Eye Infections, Bacterial; Eye Proteins; Female; Fetal Blood; Humans; Lactoferrin; Leprosy; Male; Middle Aged; Muramidase; Prospective Studies; Proteomics; Serum; Tears

With the understanding of the immune inflammatory response in the pathogenesis of dry eyes, and the limitations of widely used artificial tears and numerous pharmaceuticals and methods to promote tear secretion, clinicians pay more attention to the therapies that can promote tear secretion actively. Acupuncture treatment for dry eye may meet this requirement.. To observe the clinical efficacy of acupuncture treatment on dry eye and the effects on duration, and to examine the mechanisms of acupuncture in treating patients with dye eyes.. The study was performed at Department of Ophthalmology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine from August 2010 to May 2011. Patients with the primary diagnosis of dry eye were enrolled. Sixty-five patients were randomly divided into treatment group and control group, and were given 3 weeks of acupuncture treatment or artificial tear therapy respectively.. The enzyme-linked immunosorbent assay was used to detect the lactoferrin content of the tears before and after treatment. In order to evaluate the efficacy of the treatment methods, the Schirmer I test and break-up time were also measured.. Compared with before treatment, the lactoferrin content in the tears of patients in the treatment group increased, break-up time was prolonged and the result of the Schirmer I test showed improvement after 3 weeks of treatment. The indexes mentioned above did not change in the control group after treatment. There were no significant differences in tear lactoferrin and Schirmer I test between one week after treatment and after 3-week treatment in the treatment group, but break-up time was significantly shortened. The result of Schirmer I test in the treatment group was significantly higher than that in the control group one week after treatment.. Acupuncture can increase tear lactoferrin level, extend tear film break-up time and promote tear secretion in patients with dry eye in a time-limited trial. With the end of treatment, the effect decreased.

Topics: Acupuncture Therapy; Adult; Aged; Dry Eye Syndromes; Female; Humans; Lactoferrin; Male; Middle Aged; Ophthalmic Solutions; Tears

Differentiating dry eye disease (DED) from allergic or viral conjunctivitis rapidly and accurately is important to ensure prompt diagnosis and treatment. Tear lactoferrin (LF), a multi-functional glycoprotein found in tears, decreases significantly in patients with DED, and has been considered as a DED diagnostic biomarker. Measuring tear LF level, however, takes time and requires the use of bulky instruments. Herein, a homogeneous carbon nanostructure-based aptasensor with high sensitivity and selectivity has been developed by applying fluorescence polarization (FP) technology. The FP of carbon dots (CDs) bioconjugated with LF aptamers (CDs-aptamer) is 21.2% higher than that of CDs, which can be further amplified (1.81 times) once interacting with graphene oxide nanosheets (GONS). In the presence of LF, GONS separates from CDs-aptamer because of the stronger binding affinity between CDs-aptamer to LF, resulting in the decrease of FP value. A linear relationship is observed between FP value and LF concentration in spiked tear samples from 0.66 to 3.32 mg/mL. The selectivity of the aptasensor has been investigated by measuring other proteins. The results indicate that the FP-based aptasensor is a cost-effective method with high sensitivity and selectivity in detection of tear LF.

Topics: Carbon; Dry Eye Syndromes; Fluorescence Polarization; Humans; Lactoferrin; Oligonucleotides

Dry eye disease (DED) is a complex ocular surface inflammatory disease. Its occurrence varies widely over the world, ranging from 5% to 34%. The use of preservatives, specifically benzalkonium chloride, in the ocular drops worsens the DED conditions. Furthermore, the Covid-19 pandemic increased screen time and the use of face masks and shields. As a result, the number of people suffering from dry eye disease (DED) has increased significantly in recent years. The main objective of our study is to find a solution to manage the dry eye disease (DED) preferably from natural source without any adverse events. In this study, the beneficial effects of capsanthin from Capsicum annum (CCA) were evaluated on benzalkonium chloride (BAC)-induced dry eye disease (DED) in Albino Wistar rats. Oral supplementation of CCA resulted in a statistically significant decrease in intraocular pressure (IOP) (p < .0001), increase in tear break-up time (TBUT) (p < .01), decline in Schirmer test results (p < .01), and decrease in corneal surface inflammation (p < .01). Capsanthin ameliorated in reducing oxidative stress by increasing serum antioxidant levels such as glutathione peroxidase (GPX), nitric oxide (NO), and lactoferrin (LTF) and inhibiting matrix metalloproteinases 2 and 9 (MMP2 and MMP9) (p < .0001). Capsanthin treatment significantly inhibited the expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukins (IL-2, IL-4, IL-6), and pro-inflammatory mediator, matrix metalloproteinase-9 (MMP9). Furthermore, the lacrimal gland expressed vascular cell adhesion molecule (VCAM-1), and prostaglandin-endoperoxide synthase 2 (PTGS2) was suppressed by CCA treatment. PRACTICAL APPLICATIONS: Benzalkonium chloride (BAC), a preservative widely used in the topical ocular drug delivery system (ODDS), causes undesirable effects such as dry eye disease as well as ameliorating intraocular pressure leading to optical nerve damage and irreversible vision loss. Capsanthin from Capsicum annum (CCA) can be used to treat symptoms related to dry eye disease such as inflammation, eye irritation, visual disturbance, ocular discomfort with potential damage to the ocular surface. The CCA may be beneficial in the treatment of glaucoma, an elevated intraocular pressure. Capsanthin from C. annum can be useful in managing DED by increasing tear break-up time (TBUT), declining in Schirmer test results and decreasing in corneal surface inflammation.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Benzalkonium Compounds; Capsicum; COVID-19; Cyclooxygenase 2; Cytokines; Dry Eye Syndromes; Fruit; Gene Expression; Glutathione Peroxidase; Humans; Inflammation; Inflammation Mediators; Interleukin-2; Interleukin-4; Interleukin-6; Lactoferrin; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Nitric Oxide; Pandemics; Rats; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Xanthophylls

Lactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and the ability to modulate the gut microbiota. Expanding evidence demonstrates a crucial role of the gut microbiota in immune regulation and development. The specific composition of bacterial species of the gut has a profound influence on local and systemic inflammation, leading to a protective capacity against a number of inflammatory diseases, potentially by the induction of regulatory immune cells. In this study, we demonstrated that oral administration of lactoferrin maintains tear secretion in a restraint and desiccating stress induced mouse model of dry eye disease. Furthermore, we revealed that lactoferrin induces the reduction of inflammatory cytokines, modulates gut microbiota, and induces short-chain fatty acid production. Whereas, the antibiotic vancomycin abrogates the effects of lactoferrin on dry eye disease and significantly reduces short-chain fatty acid concentrations. Therefore, this protective effect of LF against a mice model of DED may be explained by our observations of an altered gut microbiota and an enhanced production of immunomodulatory short-chain fatty acids.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Cytokines; Disease Models, Animal; DNA, Bacterial; Dry Eye Syndromes; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Inflammation; Lactoferrin; Mice; Mice, Inbred C57BL; Protective Agents; Signal Transduction; Tears; Treatment Outcome; Vancomycin

Topics: Actins; Adult; Antigens, CD20; Biomarkers; Conjunctival Diseases; Dry Eye Syndromes; Humans; Lacrimal Apparatus Diseases; Lactoferrin; Muramidase; Prospective Studies; S100 Proteins; Stevens-Johnson Syndrome

To detect the immunohistochemical changes in the main lacrimal glands of patients suffering from chronic ocular sequelae of Stevens-Johnson syndrome (SJS).. Histological sections of biopsies from the lacrimal gland of three chronic SJS patients (mean age, 33 years; 2 males) with severe dry eye disease (Schirmer = 0 mm) were assessed using double immunofluorescence techniques. Changes in the expression of secretory proteins lactoferrin (Lf), lysozyme (Ly), aquaporin 5 (AQP5), S-100, and early apoptosis marker (Annexin V) were studied.. Different morphological expressions of secretory proteins were present in the three samples. One sample had maintained the immunoreactivity for Lf, Ly, S-100, similar to healthy controls. Two samples had significantly reduced immunoreactivity for anti-Lf, anti-Ly, and S-100, the weakest being in the sample with distorted lobular architecture and mild interlobular fibrosis. AQP5 had a distinct vesicular intracytoplasmic immunoreactivity suggesting defective trafficking and integration of the protein to the apical membrane. There was no S-100 immunostaining in the acinar or ductal epithelium, whereas interstitial nerve fibers scattered in the periacinar region showed reduced immunoreactivity for S-100. There was strong Annexin V immunoreactivity in the nuclei of epithelial cells in the majority of acinar and ductal epithelia of all the samples, with distorted nuclear morphology in one sample.. Defective trafficking of AQP5 and variable expression of Ly, Lf, S-100 are the notable findings in the lacrimal glands of chronic SJS patients along with signs of early apoptosis. It suggests that the palpebral lobe of the lacrimal gland is involved in the pathological processes occurring in the conjunctiva of SJS patients.

Topics: Adult; Annexin A5; Apoptosis; Aquaporin 5; Biomarkers; Chronic Disease; Dry Eye Syndromes; Eye Proteins; Female; Fluorescent Antibody Technique, Indirect; Humans; Lacrimal Apparatus; Lactoferrin; Male; Muramidase; S100 Proteins; Stevens-Johnson Syndrome; Young Adult

Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components to allow for SS-DED monitoring and avoid stably controlled SS-DED patients from re-entering a vicious cycle. This prospective case-control study compared stable SS-DED patients with non-SS-DED control from several aspects, including clinical indices for TF homeostasis, 2 DED diagnostic biomarkers (MMP-9 and lactoferrin), and the proteome of flush tears. Compared with non-SS-DED controls, stably controlled SS-DED subjects had less tear secretion and higher ocular surface inflammation, a higher concentration ratio of tear MMP-9/lactoferrin, a more diverse tear proteome, and lower spectral intensities of lipocalin-1, lacritin, and prolactin-inducible protein among the abundant tear proteins. For stable SS-DED patients, the concentration ratio of tear MMP-9/lactoferrin and the corrected lipocalin-1 signal was positively correlated with ocular inflammation and TF stability, respectively. MMP-9 released from stressed ocular surface epithelium and lipocalin-1 secreted from the energetic lacrimal gland are two tear biomarkers responding well to TF homeostasis. The tear proteomics approach through flush tears is a promising method for monitoring SS-DED patients with a standardized sampling procedure and lactoferrin-corrected analysis.

Topics: Biomarkers; Case-Control Studies; Dry Eye Syndromes; Eye Proteins; Female; Humans; Lactoferrin; Male; Middle Aged; Proteomics; Sjogren's Syndrome; Tears

Dry eye disease (DED) currently has no satisfactory treatment partly because of the lack of informative animal models. We evaluated the anti-inflammatory phosphosulindac (PS) for the treatment of DED using a new rabbit model of DED based on the concanavalin A (Con A) acute DED model: we injected all lacrimal glands with Con A weekly under ultrasound guidance, which prolonged DED to >3 weeks, and thoroughly assessed efficacy with tear break-up time (TBUT), tear osmolarity, Schirmer test, and tear lactoferrin levels. Rabbits with DED (n = 8-10 eyes per group) were treated topically with PS or vehicle 3×/day for 21days. PS restored TBUT, tear osmolarity, and lactoferrin levels (P < 0.0001-0.04) to normal but did not significantly improve the results of the Schirmer test. PS showed no side effects and was much more efficacious than cyclosporine or lifitegrast. In the cornea, PS suppressed the activation of nuclear factor kappa-B, the levels of transforming growth factor beta, interleukin-1 beta, interleukin-6, and interleukin-8, and the levels of matrix metalloproteinase (MMP)-1 and MMP-9, and MMP activity. Levels of prostaglandin E

Topics: Administration, Ophthalmic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Chronic Disease; Concanavalin A; Cytokines; Dinoprostone; Disease Models, Animal; Dry Eye Syndromes; Humans; Lactoferrin; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Organophosphorus Compounds; Osmolar Concentration; Rabbits; Sulindac; Tears

Meibomian gland dysfunction, but not atrophy, was associated with lower tear lactoferrin concentration, greater dry eye, and allergic symptoms, indicating greater inflammation and discomfort in patients with lower meibomian gland expressibility.. Meibomian gland dysfunction can potentially damage adjacent palpebral structures, which may induce inflammation in accessory lacrimal glands and affect lactoferrin secretion. This study aimed to examine the relationships between the severity of meibomian gland dysfunction with tear lactoferrin, conjunctival cell morphology, and clinical features of ocular allergy.. Forty subjects were divided into two groups based on the severity of meibomian gland plugging and expressibility and secondarily based on its atrophy. Dry eye and allergy questionnaires; slit-lamp examination, including lid telangiectasia; and meibography were performed. Tear lactoferrin concentration was measured using TearScan 270 MicroAssay. Impression cytology was performed on the upper palpebral conjunctiva, and goblet cell density and epithelial squamous metaplasia were quantified.. Twenty-two subjects with meibomian gland dysfunction were categorized into severely obstructed group (case), whereas 19 subjects had minimal/no obstruction (comparison). Lower lactoferrin (1.3 ± 0.4 vs. 1.7 ± 0.4 mg/mL, P = .007), greater dry eye (7 [1 to 10] vs. 2 [0 to 5], P = .03), and allergy symptoms (9 [4 to 23] vs. 6 [0 to 9], P = .05) were found in the cases compared with the comparisons. There were no differences in conjunctival cell morphology between groups. The plugging score was correlated with lactoferrin concentration (ρ = -0.43, P = .006), dry eye (ρ = 0.36, P = .02), and allergic symptoms (ρ = 0.33, P = .04). Greater lid margin telangiectasia was associated with meibomian gland obstruction, but not atrophy.. Meibomian gland activity/dysfunction, but not atrophy, may be associated with increased inflammation on the ocular surface. The inflammation may be sufficient to reduce tear lactoferrin production from damage to accessory lacrimal glands and/or meibomian gland and result in increased symptoms.

Topics: Adult; Aged; Aged, 80 and over; Blepharitis; Conjunctiva; Conjunctivitis, Allergic; Cross-Sectional Studies; Dry Eye Syndromes; Eye Proteins; Eyelid Diseases; Female; Goblet Cells; Humans; Lactoferrin; Male; Meibomian Glands; Middle Aged; Surveys and Questionnaires; Tears

The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases including dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism.

Topics: Animals; Corneal Injuries; Disease Models, Animal; Dry Eye Syndromes; Epithelial Cells; Epithelium, Corneal; Lactoferrin; Ophthalmic Solutions; Organoselenium Compounds; Oxidative Stress; Rabbits; Rats; Receptors, Cell Surface

To evaluate the clinical efficacy of 3% diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of tear proteins and mucin-like substances after the treatment.. Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins.. The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins.. Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye.

Topics: Adult; Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Dry Eye Syndromes; Eye Proteins; Female; Humans; Immunoglobulin A, Secretory; Lactoferrin; Lipocalin 1; Middle Aged; Muramidase; N-Acetylneuraminic Acid; Ophthalmic Solutions; Osmolar Concentration; Polyphosphates; Prospective Studies; Purinergic P2Y Receptor Agonists; Tears; Uracil Nucleotides; Young Adult

Among the most frequently encountered pathologies examined by the ophthalmologist is dry eye syndrome (DE), which can be discovered particularly in the elderly. The initial diagnosis of DE is of high importance, but also challenging. This is because the biochemical changes in the tear film often develop before any detectable signs.. In this study, the possible relationship between ocular symptomatology, tear volume and tear break-up time (TBUT) and lipocalin, lactoferrin and lysozyme concentrations in the tear film were explored in a group of symptomatic dry-eyed postmenopausal (PM) women compared to age-matched controls.. Sixty-six healthy PM females with ages of at least 50 years were grouped in two homogeneous lots (by age, post-menopause, co-morbidities) of 33 females each, one lot presenting mild or moderate dry eye syndrome (DE) and one asymptomatic non-dry eye (NDE), based on their feedback to the Ocular Surface Disease Index (OSDI) questionnaire and noninvasive TBUT and Schirmer test results. Tears were collected via capillary tubes and an eye wash method. Tear lysozyme, lactoferrin and lipocalin concentrations were determined via electrophoresis.. OSDI responses revealed 3 mild DE, 30 moderate DE and 33 NDE. The OSDI total score and sub scores for the DE group were significantly greater than for the NDE group (p < 0.001). The mild and moderate DE group exhibited significantly shorter TBUTs compared to NDE (p < 0.001). No difference in tear lysozyme or lipocalin concentrations was found between DE and NDE groups, irrespective of the tear collection method, but a significant difference was found in lactoferrin concentration (p<0.001). No significant correlations were found between symptoms or signs of DE compared to either lipocalin, lysozyme or lactoferrin concentrations.. In a PM population, lipocalin and lysozyme are invariable, irrespective of the presence and severity of DE symptoms. However, lactoferrin shows a significant decrease. This is a comprehensive study of lipocalin, lactoferrin and lysozyme in dry-eyed PM women and our results suggested that lactoferrin could be used as a biomarker of DE in postmenopausal women.. PM = postmenopausal; DE = dry eye disease; NDE = non-dry eye; ELISA = Enzyme-linked immunosorbent assay.

Topics: Dry Eye Syndromes; Female; Humans; Lactoferrin; Lipocalin 1; Middle Aged; Muramidase; Postmenopause; Tears

The ocular surface is strongly affected by oxidative stress, and anti-oxidative systems are maintained in corneal epithelial cells and tear fluid. Dry eye is recognized as an oxidative stress-induced disease. Selenium compound eye drops are expected to be a candidate for the treatment of dry eye. We estimated the efficacy of several selenium compounds in the treatment of dry eye using a dry eye rat model. All of the studied selenium compounds were uptaken into corneal epithelial cells in vitro. However, when the selenium compounds were administered as eye drops in the dry eye rat model, most of the selenium compounds did not show effectiveness except for Se-lactoferrin. Se-lactoferrin is a lactoferrin that we prepared that binds selenium instead of iron. Se-lactoferrin eye drops suppressed the up-regulated expression of heme oxygenase-1, cyclooxygenase-2, matrix metallopeptidase-9, and interleukin-6 and also suppressed 8-OHdG production in the cornea induced by surgical removal of the lacrimal glands. Compared with Se-lactoferrin, apolactoferrin eye drops weakly improved dry eye in high dose. The effect of Se-lactoferrin eye drops on dry eye is possibly due to the effect of selenium and also the effect of apolactoferrin. Se-lactoferrin is a candidate for the treatment of dry eye via regulation of oxidative stress in the corneal epithelium.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cells, Cultured; Cornea; Cyclooxygenase 2; Deoxyguanosine; Disease Models, Animal; Dry Eye Syndromes; Epithelial Cells; Epithelium, Corneal; Gene Expression; Heme Oxygenase-1; Humans; Interleukin-6; Lacrimal Apparatus; Lactoferrin; Male; Matrix Metalloproteinase 9; Ophthalmic Solutions; Oxidative Stress; Rats; Rats, Sprague-Dawley; Selenium

To analyze tear protein variations in patients suffering from dry eye symptoms in the presence of tear film instability but without epithelial defects.. Five microlitres of non-stimulated tears from 60 patients, suffering from evaporative dry eye (EDE) with a break-up time (BUT) <10 s, and from 30 healthy subjects as control (no symptoms, BUT >10 s) were collected. Tear proteins were separated by mono and bi-dimensional SDS-PAGE electrophoresis and characterized by immunoblotting and enzymatic digestion. Digested peptides were analyzed by liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry followed by comparative data analysis into Swiss-Prot human protein database using Mascot. Statistical analysis were performed by applying a t-test for independent data and a Mann-Whitney test for unpaired data (P<0.05).. In EDE patients vscontrols, a significant decrease in levels of lactoferrin (data in %+/-SD): 20.15+/-2.64 vs 24.56+/-3.46 (P=0.001), lipocalin-1: 14.98+/-2.70 vs 17.73+/-2.96 (P=0.0001), and lipophilin A-C: 2.89+/-1.06 vs 3.63+/-1.37 (P=0.006) was revealed, while a significant increase was observed for serum albumin: 9.45+/-1.87 vs 3.46+/-1.87 (P=0.0001). No changes for lysozyme and zinc alpha-2 glycoprotein (P=0.07 and 0.7, respectively) were shown. Proteomic analysis showed a downregulation of lipophilin A and C and lipocalin-1 in patients, which is suggested to be associated with post-translational modifications.. Data show that tear protein changes anticipate the onset of more extensive clinical signs in early stage dry eye disease.

Topics: Adipokines; Adult; Aged; Albumins; Carrier Proteins; Case-Control Studies; Dry Eye Syndromes; Electrophoresis, Polyacrylamide Gel; Eye Proteins; Female; Glycoproteins; Humans; Lactoferrin; Lipocalins; Male; Middle Aged; Muramidase; Myelin Proteins; Proteolipids; Proteomics; Secretoglobins; Tears; Uteroglobin

To determine whether intolerance to contact lens wear is attributable to clinical or protein characteristics of the tear film.. Thirty-eight subjects participated; 20 were successful contact lens wearers and 18 had discontinued contact lens wear because of discomfort. Baseline tear film (no lens wear) was analyzed with a range of clinical measurements and protein analyses (lactoferrin, sIgA, and lysozyme). Comfort was determined after 6 hours of lens wear, and differences in tear film characteristics between subject groups were determined. In half of the subject group (n = 19), discriminant analysis was used to develop an equation for predicting the likelihood of intolerance to lens wear. Sensitivity and specificity were determined by testing the formula on the remaining subjects. These formulas were also tested on a separate group of subjects enrolled in a contact lens-wearing trial.. Tear volume (meniscus height and phenol red thread test) and tear stability (noninvasive tear break up time [NI-TBUT]) were significantly reduced in intolerant wearers (P < 0.05). A greater number of symptoms were reported by intolerant than by tolerant wearers (P < 0.05). Tolerance was associated with clinical but not protein characteristics of the tear film. Formulas best able to predict contact lens intolerance included NI-TBUT, number of symptoms experienced, and tear film meniscus height. Formulas had high sensitivity, and specificity which ranged from 29% to 57%.. Contact lens intolerance appears to be best predicted by a combination of clinical variables, including tear film stability, tear volume, and symptom reporting.

Topics: Adult; Conjunctivitis; Contact Lenses; Discriminant Analysis; Dry Eye Syndromes; Eye Proteins; Female; Humans; Immunoglobulin A, Secretory; Keratitis; Lactoferrin; Male; Muramidase; Osmolar Concentration; Patient Satisfaction; Phenolsulfonphthalein; Sensitivity and Specificity; Tears

Topics: Dry Eye Syndromes; Humans; Lactoferrin; Osmolar Concentration; Prosthesis Implantation; Tears; Time Factors; Treatment Outcome

Little is known about the relationship between lachrymal and salivary gland involvement in Sjögren's syndrome (SS). It is also of interest to know which eye test contributes most to the diagnosis of SS. We investigated the performance of different tear tests and how these tests relate to common serologic and salivary tests in SS.. In patients suspected of SS, the tear breakup time and the tear mucus score were evaluated in addition to the routine tests. Eighty consecutive patients were included, categorized into primary SS (pSS), secondary SS (sSS), and negative for SS.. The tear breakup time and mucus score both performed insufficiently in diagnosing SS, in contrast to the Rose Bengal score. In pSS and sSS patients, a clear correlation was noted between tear and saliva quality and secretion rate, and between the Rose Bengal score and parotid sialography. Increased Rose Bengal scores also correlated significantly with hyperglobulinemia and presence of SSB antibodies in serum, with duration of subjective eye dryness, and with decreased tear gland function.. The Rose Bengal score remains the eye test of choice having the highest specificity for SS. Hyperglobulinemia and especially positive SSB serology may warrant close monitoring of the eyes, since these serum findings appear to relate to the severity of ocular surface damage. Theoretically, a positive evaluation of either the ocular or oral component, in addition to positive serology or histopathology, could be sufficient to diagnose the syndrome for clinical purposes.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antinuclear; Disease Progression; Dry Eye Syndromes; Female; Fluorescent Dyes; Humans; Lactoferrin; Male; Middle Aged; Mucus; Rose Bengal; Salivary Gland Diseases; Sensitivity and Specificity; Sjogren's Syndrome; Tears

To compare the expression of the pro- and anti-inflammatory forms of interleukin (IL)-1 in the tear fluid and conjunctival epithelium of normal eyes and those with dry-eye disease.. The concentrations of IL-1 alpha, IL-1 beta (precursor and mature forms), and IL-1 receptor antagonist (IL-1Ra) were measured by ELISA in tear fluid samples obtained from normal individuals and patients with dry eye who had rosacea-associated meibomian gland disease (MGD) or Sjögren's syndrome (SS) aqueous tear deficiency (ATD). These cytokines were also measured in normal tear fluid before and after nasal stimulation to induce reflex tearing. The relative expression of these cytokines was evaluated in conjunctival impression cytology specimens and conjunctival biopsy tissue obtained from normal subjects and SS ATD-affected patients using immunofluorescent staining. Matrix metalloproteinase (MMP)-9 concentration and activity in the tear fluid were evaluated with gelatin zymography and with an MMP-9 activity assay kit, respectively.. Compared with normal subjects, the concentration of IL-1 alpha and mature IL-1 beta in the tear fluid was increased, and the concentration of precursor IL-1 beta was decreased in patients with MGD (P < 0.05, P = 0.02, and P < 0.01, respectively) and SS ATD (P < 0.001, P = 0.02, and P < 0.001, respectively). There was no significant change in the concentration of IL-1 alpha, precursor IL-1 beta, and IL-1Ra in reflex tear fluid, indicating that the lacrimal glands may secrete these cytokines. The activity of MMP-9, a physiological activator of IL-1 beta, was significantly elevated in the tear fluid of both dry-eye groups compared with normal subjects. A strong positive correlation was observed between the intensity of corneal fluorescein staining and the tear fluid IL-1 alpha concentration (r(2) = 0.17, P < 0.02) and the mature-to-precursor IL-1 beta ratio (r(2) = 0.46, P < 0.001). Positive immunofluorescent staining for IL-1 alpha, mature IL-1 beta, and IL-1Ra was observed in a significantly greater percentage of conjunctival cytology specimens from eyes with SS ATD than in those from normal eyes (P < 0.01 for IL-1 alpha, P < 0.009 for mature IL-1 beta, and P < 0.05 for IL-1Ra).. Dry-eye disease is accompanied by an increase in the proinflammatory forms of IL-1 (IL-1 alpha and mature IL-1 beta) and a decrease in the biologically inactive precursor IL-1 beta in tear fluid. Increased protease activity on the ocular surface may be one mechanism by which precursor IL-1 beta is cleaved to the mature, biologically active form. The conjunctival epithelium appears to be one source of the increased concentration of IL-1 in the tear fluid of patients with dry-eye disease. These results suggest that IL-1 may play a key role in the pathogenesis of keratoconjunctivitis sicca.

Topics: Adult; Aged; Aged, 80 and over; Conjunctiva; Dry Eye Syndromes; Eye Proteins; Female; Fluorescent Antibody Technique, Indirect; Fluorophotometry; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Lactoferrin; Male; Matrix Metalloproteinase 9; Middle Aged; Sialoglycoproteins; Tears

To establish accurate measurement of tear production in the diagnosis and monitoring of dry eye.. Reexamination of the Schirmer test indicated that the rate of tear secretion decreases with advancing age. We measured the noninvasive tear film break-up time (NIBUT) in normal and dry eye patients with our original apparatus. The NIBUT showed a reasonable level of accuracy with a cut-off value of 5 seconds. The lactoferrin concentration in tear fluids subsequently was found to have a cut-off value of 1.1 mg/mL with an optimal level of accuracy.. The present findings suggest that a combination of clinical tests is needed for the diagnosis of dry eye syndrome. The closed eye condition induces subclinical inflammation on the ocular surface. Fibronectin, a high-molecular weight glycoprotein, plays an important role in corneal wound healing, although its concentration in various types of tear has not been investigated. Fibronectin concentration in open eye tears (19 +/- 24 ng/mL) was significantly different (p = 0.004) from that in closed eye tears (4127 +/- 3222 ng/mL). During reflex tearing with nasal stimulus, the concentration increased significantly (p = 0.028) after 100 mL of reflex tears (220 +/- 126 ng/mL). Albumin concentration in the same samples showed a pattern similar to that for fibronectin. Administration of a topical vasoconstrictor eliminated the increase in fibronectin concentration during reflex tearing.. These findings suggest that fibronectin in the tear fluid was derived from plasma and that the increase in concentration in closed eye and reflex tear fluid was caused by leakage from dilated conjunctival blood vessels.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albumins; Child; Child, Preschool; Dry Eye Syndromes; Eye Proteins; Female; Fibronectins; Humans; Lactoferrin; Male; Middle Aged; Tears

Decreased tear volume in patients with chronic hepatitis C has been reported in the literature. Lactoferrin is abundantly present in human tears, the main source of which is the acini of the lacrimal glands. In this study tear lactoferrin levels were measured to investigate the dry eye condition of patients with chronic hepatitis C.. Lactoferrin in tears/fluid was measured by a radial immunodiffusion assay in 42 patients with chronic hepatitis C. The rate of lacrimal secretion was determined by the cotton thread test. Rose bengal staining of the ocular surface was also performed.. Only three patients out of 42 complained of dry eye sensation and, in 31 patients, six showed positive results on the rose bengal staining test of the ocular surface. The lactoferrin concentration of tear fluid in the chronic hepatitis C group (1.42 (SD 0.56) mg/ml) was significantly lower than in the control group (1.90 (0.62) mg/ml; p <0.00048). The cotton thread test results in the chronic hepatitis C group (12.9 (5. 5) mm) were significantly lower than in the control group (17.9 (5. 3) mm; p<0.00048). Also, in the chronic hepatitis C group, tear lactoferrin concentration correlated with the results of the cotton thread test (r = 0.35, p<0.05).. Chronic hepatitis C patients showed both decreased tear volume, and decreased tear lactoferrin concentration. These findings suggest that there may be dysfunction of the lacrimal glands in patients with chronic hepatitis C, which may account for the mild dry eye.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Dry Eye Syndromes; Female; Hepatitis C; Humans; Lactoferrin; Male; Middle Aged; Tears

Human tear fluid contains lactoferrin at the highest concentration. In patients with dry eye such as Sjogren's syndrome, the concentration of lactoferrin in the tears is approximately half the normal value. The present study utilizes a short-term rabbit dry eye model to evaluate if lactoferrin containing eye drops can reverse any of the damage produced by blockage of blinking with an ocular speculum. Damage was evaluated based on the extent of methylene blue staining in histological sections. After 3 h of desiccation, the amount of extractable dye recovered following sacrifice increased by more than 4-fold in the vehicle-treated eyes. However, in those rabbits treated with 1% lactoferrin, dye recovery was only 40% of the value in the vehicle-treated eyes. Between 1-3 h and over a concentration range from 0.01 to 1% lactoferrin, the decreases in staining were both time and concentration dependent. Alternatively, if 1% lactoferrin was applied during the desiccation period, there was partial restoration of corneal epithelial integrity. These results suggest that lactoferrin may be of therapeutic value in decreasing the loss of corneal epithelial integrity in dry eye.

Topics: Animals; Coloring Agents; Dry Eye Syndromes; Epithelium, Corneal; Lactoferrin; Male; Methylene Blue; Muramidase; Ophthalmic Solutions; Rabbits; Serum Albumin, Bovine; Staining and Labeling

Despite the high frequency and clinical relevance of blepharitis-associated dry-eye syndrome, no agreement exists about whether diagnostic tests should be performed with or without topical anesthesia. The aim of this study was to compare the influence of topical anesthesia on the mean values of Schirmer's test, tear lysozyme, tear lactoferrin, and tear osmolarity in patients suffering from blepharitis-associated dry eye syndrome.. The authors compared the mean values of Schirmer's test, tear osmolarity, tear lysozyme (turbidimetric assay), and tear lactoferrin (radial immunodiffusion) before and after topical anesthesia in the following groups: 56 normal subjects (group 1), 62 blepharitis patients (group 2), and 15 patients with blepharitis-associated dry eye syndrome (group 3). All clinical and laboratory tests were performed by masked observers.. In group I, mean values of Schirmer's test decreased 24.8% (p < 0.01) when performed after application of topical anesthesia. The other tests were not significantly modified. In groups 2 and 3, significant differences were seen in Schirmer's test (25.33% and 24.19% respectively, p < 0.001) and the lysozyme determination (14.00% and 13.22% respectively, p < 0.01). Differences between the normal subjects (group I) and the patient groups increased when the tests were performed after application of topical anesthesia reaching statistical significance in group 3 for all the tests.. Performing diagnostic tests after topical anesthesia instillation could be useful in detecting dry eye associated with blepharitis.

Topics: Adrenergic alpha-Agonists; Adult; Anesthesia, Local; Anesthetics, Local; Blepharitis; Drug Combinations; Dry Eye Syndromes; Female; Humans; Lactoferrin; Male; Middle Aged; Muramidase; Naphazoline; Ophthalmic Solutions; Osmolar Concentration; Tears; Tetracaine

The lacrimal film contains 6 to 10 g/l of proteins, 99% of which locally synthesized by the lacrimal glands. The study of these proteins allows us to explore the lacrimal function and to reveal an inflammatory process.. The lacrimal proteinic profile included the determination of total proteins and electrophoresis on agarose gel and, if necessary, specific determinations of albumin, lactoferrin, lysozyme and immunoglobulins using a nephelemetric technique. Normal values were established on a hundred of individual tears.. The electrophoretic proteinic profile may present different abnormalities, such as an inflammatory process, a functional alteration of the lacrimal glands or a dysproteinic abnormality of the tears. The specific determination of the principal lacrimal proteins allows us to accurately quantify each of them.. The electrophoresis of the tears on an agarose gel reveals the presence of an inflammatory process or the quantitative or qualitative alteration of the lacrimal function. The immuno-nephelemetric determination of the most important proteins which are involved in theses mechanisms gives an accurate quantitative measurement of proteins and allows biological follow-up of the disease.

Topics: Albumins; Blood-Aqueous Barrier; Conjunctivitis; Dry Eye Syndromes; Electrophoresis, Agar Gel; Humans; Immunoglobulin A; Lacrimal Apparatus; Lactoferrin; Muramidase; Proteins; Tears

We studied the relationship between the severity of ocular surface damage and the level of tear lactoferrin in primary and secondary Sjögren's syndrome and keratoconjunctivitis sicca not associated with Sjögren's syndrome. A significant negative correlation was found between Rose Bengal staining score and level of tear lactoferrin in all three groups. Analysis of covariance disclosed no significant differences in regression lines for Rose Bengal staining score vs tear lactoferrin level among the three groups. The three regression lines appeared to be identical to each other. These findings indicate that the severity of ocular surface damage due to dry eye largely depends on the tear secretory function of the lacrimal gland, and that the function of the lacrimal gland can be evaluated by determination of level of tear lactoferrin using the same standards regardless of differences in pathogenesis of underlying diseases.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Dry Eye Syndromes; Eye Proteins; Female; Humans; Keratoconjunctivitis Sicca; Lactoferrin; Male; Middle Aged; Rose Bengal; Sjogren's Syndrome; Tears

To establish a definitive set of diagnostic criteria in a multicentre European study a selected number of oral and ocular tests were performed on a large number of patients with Sjögrens Syndrome (SS) and controls. The diagnostic accuracy of each test for patients with primary and secondary SS and for controls at different ages, was studied.. Each centre received a clinical chart describing the series of tests to be conducted. The tests included: questionnaires for dry eye and dry mouth symptoms, Schirmer's-I-test (ScT), tear fluid lactoferrin level (TFLL), break-up time (BUT) and rose Bengal score (RBS) for the eye evaluation; unstimulated and stimulated whole saliva collection (UWSC and SWSC), salivary gland scintigraphy (SGS), parotid sialography (PS) and minor salivary gland biopsy (MSGB) for oral involvement.. Data from 22 centres and 11 countries was collected on a total of 447 patients with SS (246 with primary SS and 201 with secondary SS) and 246 controls (of whom 113 had a connective tissue disease without SS). Among the ocular symptoms, the feeling of dry eye and 'sand in the eye' were the ones most commonly recorded in patients with SS. Similarly, the feeling of dry mouth, appearing either spontaneously or when the patient was eating or breathing, was the most frequent subjective oral symptom. Among the ocular tests, ScT showed the best balance between sensitivity and specificity (76.9% and 72.4% respectively), while RBS was the most specific test (81.7%). ScT and RBS gave also sufficiently concordant results. TFLL and BUT gave considerably less reliable results, which were not concordant with each other or with the other ocular tests. The quantitative lacrimal tests ScT and TFLL produced significantly different results in elderly controls, while RBS did not. Abnormal results for all of the ocular tests were less marked and less frequent in patients with secondary SS than in those with primary SS. The oral tests (except SWSC) were generally more reliable than the ocular tests in diagnosing SS. In particular, PS was the most specific diagnostic tools (100%), while MSGB (where the presence of at least one inflammatory focus was considered as indicative for the diagnosis) showed a good balance between sensitivity and specificity (82.4% and 86.2%, respectively). The tests showed a good degree of agreement, and, with the exception of UWSC, were not influenced by age. In the oral, as in the ocular tests, abnormal results were less frequent and less marked in patients with secondary SS.. The results clearly show that ScT and RBS (for the eye evaluation), and SGS, PS, MSGB and UWSC (for salivary gland involvement) are the most reliable tests for the diagnosis of SS. The clinician should be aware, however, that the test results may vary depending on the age of the patient and the type of SS (primary or secondary).

Topics: Adult; Age Factors; Aged; Dry Eye Syndromes; Eye Diseases; Female; Humans; Lactoferrin; Male; Middle Aged; Mouth Diseases; Parotid Gland; Radiography; Radionuclide Imaging; Saliva; Salivary Glands; Sensation Disorders; Sensitivity and Specificity; Sjogren's Syndrome; Tears

Diagnoses of dry eye made with the Lactoplate Immunoassay Test (which assesses tear lactoferrin concentration) were compared to diagnoses based on dry eye symptoms, tear break-up times, and rose bengal staining. For a population of 49 subjects with normal and mild to moderate dry eyes, contingency tables showed that the lactoferrin-based diagnoses were not significantly related to the diagnoses made using any of the other factors. Lactoferrin concentrations were statistically correlated with symptom scores, but there was no significant correlation between lactoferrin concentrations and either tear break-up time or rose bengal staining. These results suggest that: 1) the dry eye problems in the subject population may not have been associated with lacrimal gland dysfunction (which the Lactoplate assesses); 2) Lactoplate tests are not sensitive enough to allow accurate diagnoses for the population of mild to moderate dry eye subjects used; 3) signs and symptoms associated with dry eyes occur before lactoferrin changes are manifest so lactoferrin changes had not yet appeared in the subjects; or 4) in mild to moderate dry eye subjects, lactoferrin changes occur only in reflexive tears and not in the basal tears that were tested in this study. In summary, measurement of tear lactoferrin concentration alone has not been shown to be a sufficiently sensitive and specific test for the diagnosis of mild to moderately dry eye as defined by more common clinical techniques.

Topics: Adult; Aged; Aged, 80 and over; Dry Eye Syndromes; Female; Humans; Lactoferrin; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Tears