Effect of ocular demodicosis on the stability of the tear film and the tear break up time.

The aim of the study was to analyze the correlation between the presence of Demodex mites in the hair follicles of patients' eyelashes and the stability and break up time of the tear film assessed with the Non-Invasive Tear Break Up Times (NIBUT) method. 319 patients were included in the study (195 women, 124 men). The patients were divided into two groups: those with Demodex infestation and without visible symptoms of eyelid or eye surface diseases, and asymptomatic non-infested patients. The NIBUT analysis was performed with a 5 M keratograph (oculus). Non-invasive tests were performed to identify the first and mean values of the tear break up time. The first and mean tear break up time in the Demodex-infested group was lower than in the non-infested subjects. The difference was a highly statistically significant. There was a significant correlation with the age of the patients for the first break up time. The first break up time in both eyes decreased with the age of the Demodex-infested and non-infested patients. The NIBUT analyses indicate the impact of Demodex mites on the tear film stability. This may suggest possible association of demodicosis with dry eye syndrome.

Ocular Graft-versus-Host Disease in a Chemotherapy-Based Minor-Mismatch Mouse Model Features Corneal (Lymph-) Angiogenesis.

Ocular graft-versus-host disease (oGVHD) is a fast progressing, autoimmunological disease following hematopoietic stem cell transplantation, leading to severe inflammation of the eye and destruction of the lacrimal functional unit with consecutive sight-threatening consequences. The therapeutic "window of opportunity" is narrow, and current treatment options are limited and often insufficient. To achieve new insights into the pathogenesis and to develop new therapeutic approaches, clinically relevant models of oGVHD are desirable. In this study, the ocular phenotype was described in a murine, chemotherapy-based, minor-mismatch GVHD model mimicking early-onset chronic oGVHD, with corneal epitheliopathy, inflammation of the lacrimal glands, and blepharitis. Additionally, corneal lymphangiogenesis was observed as part of oGVHD pathogenesis for the first time, thus opening up the investigation of lymphangiogenesis as a potential therapeutic and diagnostic tool.

Efficacy of Intense Pulsed Light Treatment for Moderate to Severe Acute Blepharitis or Blepharoconjunctivitis: A Retrospective Case Series

Objectives: We aimed to evaluate the efficacy of periocular intense pulsed light (IPL) therapy in the treatment of moderate to severe acute blepharitis or blepharoconjunctivitis. Materials and Methods: This was a retrospective study performed in one institution. Eleven patients who received bilateral periocular IPL therapy using an IPL device (E>Eye, ESwin, Paris, France) were retrospectively evaluated. The following findings obtained at baseline and 10 weeks after the treatment were recorded: slit-lamp examinations; symptom scores of the Compression of the Eyelid (COTE) grading system and Ocular Surface Disease Index (OSDI); ocular surface staining with Oxford grading scale (OXFORD) scores; lipid layer thickness (LLT); and non-invasive tear meniscus test (TMH), non-invasive break up time measurement (NIBUT), and meibography performed by using I.C.P. Ocular Surface Analyzer (SBM System, Turin, Italy). Results: Significant improvements in OSDI symptom scores (p<0.0001), LLT (p<0.0001), and meibography (p<0.0001) were obtained at 10 weeks after bilateral periocular IPL therapy. COTE and ocular surface staining scores decreased by 59.72% and 57.14% respectively, while NIBUT and TMH increased by 47.34% and 22.16%, respectively. In parallel to the improvement in OSDI, LLT, and meibography, findings of acute blepharitis or blepharoconjunctivitis improved in slit-lamp examination. There were no adverse effects. Conclusion: Serial IPL therapy improves the clinical signs and symptoms of moderate to severe acute blepharitis or blepharoconjunctivitis, meibomian gland morphology, and secretion quality.

Effect of 808-nm Laser Photobiomodulation Treatment in Blepharitis Rat Model.

PURPOSE: Blepharitis, simply defined as eyelid inflammation, is one of the common ocular conditions associated with discomfort and irritation. Because blepharitis causes meibomian gland dysfunction and dry eye, this study aimed to confirm the effect of photobiomodulation (PBM) on blepharitis. METHODS: A total of 20 rats were randomly assigned to 4 equal groups, including control, blepharitis, PBM, and eye drop. Blepharitis was induced in rats by injecting complete Freund's adjuvant in the eyelid margins. PBM intervention was given every 3 days after blepharitis induction. Clinical signs including tear volume, tear breakup time (TBUT), meibomian gland swelling, fluorescein, telangiectasia, and meibomian gland secretion scores were measured every week, and the rats were killed for histological analysis after 4 weeks. Immunohistochemistry was performed to compare the level of inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining on retina was performed to observe any retinal damage. RESULTS: Tear volume and TBUT increased with PBM intervention, and with improved eyelid swelling, corneal staining, telangiectasia, and meibomian gland secretion scores increased. Hematoxylin and eosin staining showed no structural abnormalities of meibomian gland caused by blepharitis induction. Immunohistochemistry revealed that the levels of inflammatory cytokines interleukin-1ß and tumor necrosis factor-α were lowered with PBM treatment in both eyelid and conjunctiva. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed no retinal damage. CONCLUSIONS: Laser PBM at 808 nm was effective in alleviating ocular signs and controlling inflammation in blepharitis rat model. The in vivo results suggest that PBM has the potential to be used in treating blepharitis patients.

Clinical efficacy of eyelid hygiene in blepharitis and meibomian gland dysfunction after cataract surgery: a randomized controlled pilot trial.

The purpose of this randomized clinical trial is to evaluate the effect of eyelid hygiene on subjective symptoms, anterior blepharitis, and meibomian gland dysfunction (MGD) after cataract surgery. Subjects with obstructive MGD who underwent cataract surgery were randomly divided into two groups. In the eyelid hygiene group, eyelid hygiene was performed twice a day for 10 days from 3 days before to 1 week after cataract surgery. The control group did not perform eyelid hygiene. A subjective symptom questionnaire of SPEED, anterior blepharitis grade, and meibum quality and quantity was evaluated at baseline and at postoperative 1 and 4 weeks. The eyelid hygiene group (n = 36) showed decreased SPEED score after cataract surgery and the control group (n = 33) did not. Anterior blepharitis grade was worse 1 week after surgery in the control group but not in the eyelid hygiene group. The control group had significantly decreased meibum quality and quantity in both the upper and lower eyelids after cataract surgery, but the eyelid hygiene group did not. Eyelid hygiene before/after cataract surgery improved postoperative subjective symptoms and prevented postoperative exacerbation of anterior blepharitis and MGD. Thus, perioperative eyelid hygiene is recommended for patients with obstructive MGD who undergo cataract surgery.

Comparison of Efficacy and Safety of Two Tea Tree Oil-Based Formulations in Patients with Chronic Blepharitis: A Double-Blinded Randomized Clinical Trial.

INTRODUCTION: It was aimed to evaluate the efficacy of two tea tree oil (TTO)-based cleansing gels in chronic blepharitis patients. METHODS: Group-1 (basic gel containing 3%(w/w)-TTO) included 50 eyes of 25 patients and group-2 (advanced gel containing 3%(w/w)-TTO plus essential oils and vitamins) included 48 eyes of 24 patients. Ocular Surface Disease Index (OSDI), tear breakup time (TBUT), ocular surface staining pattern, Schirmer's test, impression cytology, Demodex presence and TNF-α, IL-6, IL-1ß levels were evaluated at the first visit and 1 month after treatment. RESULTS: In both groups, the mean OSDI score decreased (p1:0.001, p2:0.001), TBUT increased (p1:0.002, p2:0.004). In group-1, Demodex presence decreased from 42% to 27.8%; in group-2 from 54.2% to 20.6% (p1:0.302, p2:0.004). IL-1ß and IL-6 decreased in group-2 (p1:0.002, p2:0.050). TNF-α decreased in both groups (p1:0.001, p2:0.001). CONCLUSION: Both formulations improved ocular surface parameters. Group 2 showed more reduction in tear cytokines and Demodex count.

Human Meibum Cholesteryl and Wax Ester Variability With Age, Sex, and Meibomian Gland Dysfunction.

Purpose: Relationships between tear film lipid (TFL) layer composition, structure, and function could provide insight into the etiology of dry eye. The molar ratio of cholesteryl ester (CE)/wax ester (WE) was measured in meibum from normal donors (Mn) and compared with meibum from donors with meibomian gland dysfunction (MMGD). Methods: CE/WE was measured using nuclear magnetic resonance spectroscopy. Results: CE/WE was distributed into two populations with 81% distributed near 0.55 and 19% near 0.3. CE/WE were higher in donors 13 to 19 years old compared with donors 1 to 12 years old and 20 to 88 years old. CE/WE for MMGD was 30% lower, 0.34 ± 0.04, compared with Mn, 0.49 ± 0.04. There were no sex differences in CE/WE. There were no significant racial differences between the CE/WE ratios for Asians and Caucasians. The CE/WE ratio was higher for blacks and lower for Hispanics compared to Caucasians. Due to the small number sampled, confirmation of the later racial results is needed. The packing of CE and WE in the TFL layer was proposed. Conclusions: Although MMGD contains much less CE than Mn, factors other than the CE content, such as the levels of saturation and/or proteins, may be responsible for the higher order of MMGD. In addition to saturation, CE could contribute to the increase in order of Mn between 0 and 20 years of age. Observed changes in the meibum content of CE alone is not likely to influence tear film stability.

Evaluation of Long-Term Silicone Hydrogel Use on Ocular Surface Inflammation and Tear Function in Patients With and Without Meibomian Gland Dysfunction.

OBJECTIVES: To determine whether silicone hydrogel (SH) contact lens (CL) use, with or without meibomian gland dysfunction (MGD), promotes ocular surface inflammation. METHODS: Subjects wearing SH-CL for at least 6 months who also had coexisting MGD (group 1, n=20), SH-CL users who did not have MGD (group 2, n=20), patients who had MGD but did not use CL (group 3, n=20), and healthy CL-naive individuals with no known systemic or ocular diseases (group 4, n=20) were included in this cross-sectional, single-center study. All subjects underwent tear function tests consisting of tear break-up time (tBUT), ocular surface staining, Schirmer test, and the Ocular Surface Disease Index (OSDI) questionnaire, as well as determination of tear IL-1RA, IL-1ß, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, granulocyte-macrophage colony-stimulating factor, IP-10, monokine induced by gamma interferon, RANTES, eotaxin, MIP-1α, MIP-1ß, and MCP-1 levels using Luminex multicytokine immunobead assay. Intergroup comparisons were made using one-way analysis of variance or Kruskal-Wallis test. RESULTS: The tBUT was lower (P=0.048) and ocular surface staining (P=0.032) as well as OSDI scores (P=0.001) were higher in group 1 but not in groups 2 or 3 when compared with those in the control group. Tear cytokine levels were similar across all groups. None of the tear cytokine levels were elevated in CL wearers (groups 1 and 2) or those with MGD (groups 1 and 3) as compared to those in control subjects. CONCLUSION: Silicone hydrogel contact lens use with concomitant MGD is not associated with cytokine-driven ocular surface inflammation but may impact tear function leading to dry eye symptoms.

Tear Lactoferrin and Features of Ocular Allergy in Different Severities of Meibomian Gland Dysfunction.

SIGNIFICANCE: 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. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Relationship between blepharitis and components of the metabolic syndrome. / Relación entre blefaritis y componentes del síndrome metabólico.

OBJECTIVE: To determine the relationship between the components of the metabolic syndrome with the presence of blepharitis. METHODS: The study included 60 patients with a diagnosis of blepharitis and 30 control subjects. Anthropometric measurements and blood pressure were recorded, and peripheral venous blood samples were obtained under fasting conditions to determine the concentration of Glucose, Cholesterol, and Triglycerides. High-density lipoprotein cholesterol (HDL-C) was determined after precipitating lipoproteins containing apoB-100 with phosphotungstic acid/Mg2+. The concentration of low density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula modified by DeLong. RESULTS: In the comparative analysis, statistically significant differences were found in the waist circumference (P=.0491), systolic blood pressure (P=.0149), glucose (P=.0045), total cholesterol (P=.0001), HDL-C (P=.0049), LDL-C (P=.0266), and triglycerides (P=.0059); while there was no significant differences in the BMI or the diastolic pressure. CONCLUSIONS: The results support the hypothesis that the metabolic syndrome could be considered a risk factor for the development of blepharitis, and its timely detection is essential to avoid future complications.

Drugs - Do we need them? Applications of non-pharmaceutical therapy in anterior eye disease: A review.

Natural products have been in use long before the introduction of modern drug therapies and are still used in various communities worldwide for the treatment of anterior eye disease. The aim of this review is to look at the current non-pharmaceutical modalities that have been tried and assess the body of existing evidence behind them. This includes alternative medicine, existing non-pharmaceutical therapy and more recent low and high tech solutions. A detailed search of all available databases including MEDLINE, Pubmed and Google was made to look for English-language studies for complementary and alternative treatment modalities (CAM), natural therapies and new modalities for anterior eye disease such as blepharitis, dry eye and microbial keratitis. We have included a broad discussion ranging from traditional treatments like honey and aloe vera which have been used for centuries, to the more recent technological advances like Intense Pulsed Light (IPL), LipiFlow and photoactivated chromophore for corneal cross linking in infectious keratitis (PACK-CXL). Alternative management strategies may have a role in anterior eye diseases and have a potential in changing the way we currently approach them. Some of the available CAM could play a role if incorporated in to current management practices of not only chronic diseases like blepharitis and dry eye, but also acute conditions with significant morbidity like microbial keratitis. Further large-scale randomized control trials stratified by disease severity are required to improve our understanding and to evaluate the use of non-pharmaceutical therapy against current practice.

The evaluation of meibomian gland function, morphology and related medical history in Asian adult blepharokeratoconjunctivitis patients.

PURPOSE: To evaluate the meibomian gland function, morphology and the related medical history of patients with blepharokeratoconjunctivitis (BKC) in comparison with healthy population and meibomian gland dysfunction (MGD)-induced evaporative dry eye (EDE) patients. METHODS: Twenty-two eyes of 22 Asian adult patients with BKC were enrolled as the BKC group. Healthy volunteers and MGD-induced EDE patients were recruited in a 1:1 ratio and were matched in age, and the gender compositions of the three groups were also comparable. Examinations included meibum quality, meibomian gland expressibility, meibomian gland dropout and relevant ocular surface tests. Related medical history was recorded. RESULTS: The BKC group had higher incidences of chalazion (OR 4.59, 95% CI 1.29-16.33) and eyelid surgery (OR 4.91, 95% CI 1.33-18.21) than the control group (chalazion, p = 0.007; eyelid surgery, p < 0.001) and EDE group (chalazion, p = 0.031; eyelid surgery, p = 0.005) had. All clinical indexes were worse in the BKC group than in the control group (all p < 0.05). The EDE group had better meibum quality (p = 0.049) and less meibomian gland dropouts (all p < 0.05) than the BKC group. The dropouts of the BKC group were the highest among the three groups, and the distribution over the tarsal plate was even in the BKC group (all p > 0.05). CONCLUSIONS: Patients with BKC had worse meibomian gland function, poorer morphology and a higher rate of medical histories related to the meibomian gland than the healthy population. The BKC clinical features of meibum quality and meibomian gland dropout were different from other MGD diseases.

STAT6-mediated keratitis and blepharitis: a novel murine model of ocular atopic dermatitis.

PURPOSE: Atopic dermatitis (AD) is a common inflammatory disease that can affect the eye, resulting in ocular pathologies, including blepharitis, keratitis, and uveitis; however, the pathogenic mechanisms underlying the ocular manifestations of AD are not well understood. METHODS: In the present study, we characterized the ocular pathologies that develop in the Stat6VT mouse model of AD. We examined the cytokine profile of the eyelid lesions, measured the behavioral response, and documented the treatment response to topical steroids. RESULTS: Our results show that Stat6VT mice spontaneously developed blepharitis, keratitis, and uveitis similar to that observed in patients with AD. Histologic findings of allergic inflammation in affected eyelids in this model include the presence of a lymphocyte-predominant infiltrate and tissue eosinophilia in the dermis. Gene expression analysis of affected eyelid tissue by quantitative PCR revealed increased amounts of mRNAs for the Th2 cytokines IL-4, IL-5, and IL-13. In addition, increased eyelid scratching was seen in Stat6VT mice with blepharitis. Topical treatment with the corticosteroid clobetasol reduced eyelid inflammation, tissue eosinophilia, and Th2 cytokine expression. CONCLUSIONS: The development of AD-like ocular pathologies in this model supports the idea that in humans, AD-associated disease of the eye may be driven by Th2-mediated inflammation and demonstrates that the Stat6VT mouse may be a useful system in which to further investigate pathogenesis of and treatment strategies for blepharitis and other ocular diseases that develop in association with AD.

Tear cathepsin S as a candidate biomarker for Sjögren's syndrome.

OBJECTIVE: The diagnosis of Sjögren's syndrome (SS) in routine practice is largely a clinical one and requires a high index of suspicion by the treating physician. This great dependence on clinical judgment frequently leads to delayed diagnosis or misdiagnosis. Tear protein profiles have been proposed as simple and reliable biomarkers for the diagnosis of SS. Given that cathepsin S activity is increased in the lacrimal glands and tears of NOD mice (a murine model of SS), the aim of this study was to explore the clinical utility of using tear cathepsin S (CTSS) activity as a biomarker for SS. METHODS: A method to measure CTSS activity in tears eluted from Schirmer's test strips was developed and validated. Schirmer's tests were performed and CTSS activity measurements were obtained in 278 female subjects, including 73 with SS, 79 with rheumatoid arthritis, 40 with systemic lupus erythematosus, 10 with blepharitis, 31 with nonspecific dry eye disease, and 12 with other autoimmune diseases, as well as 33 healthy control subjects. RESULTS: The median tear CTSS activity in patients with SS was 4.1-fold higher than that in patients with other autoimmune diseases, 2.1-fold higher than that in patients with nonspecific dry eye disease, and 41.1-fold higher than that in healthy control subjects. Tear CTSS levels were equally elevated in patients with primary SS and those with secondary SS, independent of the Schirmer's test strip values or the levels of circulating anti-SSA or anti-SSB antibodies. CONCLUSION: Markedly high levels of tear CTSS activity are suggestive of SS. CTSS activity in tears can be measured in a simple, quick, economical, and noninvasive manner and may serve as a novel biomarker for autoimmune dacryoadenitis during the diagnostic evaluation for SS.

Fas deficiency in mice with the Balb/c background induces blepharitis with allergic inflammation and hyper-IgE production in conjunction with severe autoimmune disease.

Fas (CD95) is a cell surface death receptor belonging to the tumor necrosis factor receptor superfamily, which mediates apoptosis-inducing signaling when activated by Fas ligand or its agonistic antibody. lpr mice with a loss of apoptosis-inducing function mutation in the Fas gene develop systemic autoimmune disease and lymphadenopathy but not allergic inflammation. In the case of Fas mutations including lpr and knockout (KO), background genes determine the incidence and severity of lymphadenopathy and histopathological manifestation of systemic autoimmunity: MRL-lpr/lpr mice and C57BL/6-lpr/lpr or C57BL/6 Fas KO mice develop severe and minimum disease, respectively. We generated Fas KO mice with the Balb/c background that show severer autoimmune phenotypes than MRL-lpr/lpr mice, such as critical infiltration of mononuclear cells into lung, liver and spleen, elevated serum levels of auto-antibodies and a decreased life span. To our astonishment, Balb/c Fas KO mice spontaneously develop blepharitis with not only autoimmune inflammation with deposition of auto-antibody but also allergic inflammation with infiltration by eosinophils and mast cells and show the capacity to strongly increase serum level of IgE and IgG1 along with their aging. Thus, Fas expression regulates development of not only autoimmune disease but also allergic inflammation.

Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication.

PURPOSE: The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment. METHODS: A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits. RESULTS: Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. CONCLUSIONS: Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.

Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis.

PURPOSE: To evaluate the effect of 4 weeks of treatment with azithromycin ophthalmic solution 1% on eyelid bacterial load, tear cytokines, and signs and symptoms of blepharitis. METHODS: Twenty-six subjects (mean age 64.2 years; 65% female; 100% white) with moderate to severe blepharitis received azithromycin ophthalmic solution 1% in the absence of warm compresses or eyelid scrubs for 28 days (twice a day on days 1 and 2 and once a day on days 3-28). Blepharitis signs and symptoms were evaluated at baseline (day 1) and compared with end of treatment (day 29) and 2 follow-up visits (2 and 4 weeks posttreatment). Tear collection and eyelid margin bacterial cultures were performed at baseline and end of treatment. Tear cytokines were measured by a multiplex immunobead assay. RESULTS: Four-week azithromycin treatment demonstrated significant decreases from baseline in investigator-rated signs of meibomian gland plugging, eyelid margin redness, palpebral conjunctival redness, and ocular discharge (P < or = 0.002) at day 29, which persisted 4 weeks posttreatment (P < or = 0.006). Subject-reported symptoms of eyelid itching, foreign body sensation/sandiness/grittiness, ocular dryness, ocular burning/pain, and swollen/heavy eyelids also demonstrated significant improvement from baseline (P < 0.001 for all symptoms and time points, except P = 0.037 for ocular dryness at visit 4). Eyelid margin culture exhibited significant decreases in coagulase-negative staphylococci and Corynebacterium xerosis bacteria. Changes in tear cytokine concentrations were not observed. Twelve subjects experienced 19 adverse events, 15 of which were ocular and none of which were serious. CONCLUSIONS: Azithromycin provided significant improvement in signs and symptoms of blepharitis after 4 weeks of treatment compared with baseline and persisted in the 4-week follow-up period.

Branched-chain fatty acids, increased in tears of blepharitis patients, are not toxic for conjunctival cells.

AIM: The composition of the meibum of blepharitis patients is characterised by increased levels of branched-chain fatty acids (BCFAs) that return to normal values in patients treated with cyclins and lid hygiene. The aim of this study was to determine if BCFAs had toxic effects on conjunctival cells related to the disease. METHODS: Chang and IOBA-NHC conjunctival human cells were treated with BCFAs (isoC16 and isoC20) or palmitic acid as a control for 4 h or 24 h at 50 microM or 100 microM. Morphological and functional changes were investigated by measuring mitochondrial dehydrogenase activity, cell permeability, mitochondrial depolarisation, chromatin condensation, IL-1beta and reactive oxygen species production. RESULTS: None of the fatty acids modified the parameters of cytotoxicity in conjunctival cells in Chang or IOBA-NHC cell lines. Only the mitochondrial dehydrogenase activity was significantly decreased in relation to the isoC20 concentration increase. CONCLUSIONS: The increase in BCFAs in the tears of blepharitis patients does not consistently participate in the conjunctival cell changes throughout the course of the disease. Instead, it is likely an adaptive response of the ocular surface to the lack of tears, possibly increasing meibum fluidity, thus enhancing lacrimal film stability.

Compositional profiling and biomarker identification of the tear film.

Identification of tear film proteins and lipids is important for the elucidation of contact lens incompatibilities, tear film instabilities, dry eye syndromes, and other eye diseases. Compositional analysis of the tear film has been hampered in the past by the complex nature of the fluid and small sample size. Previously, all analytical methods required pooling of tear samples and molecular manipulation for detection of proteins and lipids, all of which skewed the resultant data. With the advent of nanoscale detection and analysis methods, it has become possible to identify specific tear components. This paper reviews the recent advances in tear sampling, proteomics, and lipidomics. Compositional profiling techniques, such as multi-dimensional electrophoresis, high performance liquid chromatography, and mass spectrometry, are assessed. Application of these techniques to identify potential biomarkers for specific tear disease conditions, such as blepharitis and dry eye, are evaluated.

Inflammatory markers in the tears of patients with ocular surface disease.

PURPOSE: To determine the concentration of interleukins (IL-1beta and -6) and matrix metalloproteinase 9 (pro-MMP-9) in the tears of patients with different ocular surface diseases and to examine the possible relationship between the disorders and molecular inflammation. METHODS: 77 patients diagnosed as having different ocular surface disorders and 18 normal control subjects were studied. Patients were routinely examined and separated into 5 groups: (1) control, (2) blepharitis, (3) ocular allergic disease, (4) dry eye and (5) conjunctivochalasis. Ten microliters of tears were collected by a Weck cell sponge. The concentrations of IL-1beta, IL-6 and pro-MMP-9 were measured by enzyme-linked immunosorbent assay, and the MMP-9 activity was evaluated with gelatin zymography. RESULTS: Levels of IL-1beta and IL-6 in tear fluid were significantly higher in conjunctivochalasis (p = 0.0062 and p = 0.0134) than in the control group. Pro-MMP-9 levels were significantly elevated in blepharitis (p = 0.013), in allergic eye disease, in dry eye and in conjunctivochalasis (all p < 0.001), in comparison to controls. CONCLUSIONS: Pro-MMP-9 levels in tears are elevated in all of the studied pathologies especially in ocular allergy and conjunctivochalasis. However, IL-1beta and IL-6 were only found to be overexpressed in conjunctivochalasis. These findings illustrate the selective implication of different molecules in each disorder.