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Prevalence and treatment of Helicobacter pylori in patients with blepharitis.
PURPOSE: Helicobacter pylori is a major pathogen etiologically associated with gastritis, peptic ulcer disease, gastric cancer, and primary gastric lymphoma. This study was conducted to investigate a possible association between Helicobacter pylori infection and blepharitis. Two hundred fifty consecutive patients with symptomatic blepharitis and 250 control subjects without blepharitis symptoms were evaluated. After exclusions, the blepharitis group consisted of 186 patients with blepharitis and a control group of 215 patients. METHODS: Blepharitis was diagnosed on the basis of findings in ophthalmic and dermatologic examinations. All patients underwent a 13C-urea breath test (UBT) to detect H. pylori infection, and impression cytology was performed before and after eradication therapy. The follow-up period was 4 months +/- 28 days. RESULTS: The blepharitis group showed an H. pylori infection prevalence of approximately 76.3% (UBT-positive group with blepharitis: n = 142 patients), compared with 42.3% of the control group (UBT-positive group with blepharitis [although asymptomatic]: n = 66 patients; UBT-positive group without blepharitis: n = 25 patients). Furthermore, we observed blepharitis in 30.6% (n = 66 patients) of UBT-positive control subjects and 13.4% (n = 29 patients) of UBT-negative control subjects. Impression cytology revealed that blepharitis was more severe in UBT-positive patients than in negative ones, and a clinical improvement in blepharitis was noted in approximately 50% of patients after H. pylori eradication. CONCLUSIONS: Even though possible sources of error in defining the association of two highly prevalent conditions must be considered, the data seem to validate an association between H. pylori infection and blepharitis, but may not be indicative of a causal association. Eradication of H. pylori improved ocular cytology results. It is possible that chronic blepharitis is an extradigestive manifestation of H. pylori infection.
[Blepharitis. Demodex folliculorum, associated pathogen spectrum and specific therapy].
UNLABELLED: Demodex folliculorum has been demonstrated with an elevated frequency in patients with blepharitis, and is thought to cause therapy-resistant blepharitis. This paper presents the germ spectrum of patients with blepharitis and demodex and discusses the efficiency of a specific therapy. METHODS: In all, 3152 cilia from 139 patients with blepharitis (38% blepharitis, 44% blepharoconjunctivitis, others) and 108 persons with quiet eyes were examined for demodex. Smears n = 125, from the conjunctive of symptomatic patients were investigated for bacteria, 3 weeks of therapy with mercury ointment, 2%: Lindan, cortisone (prednisolone, dexamethasone, hydrocortisone, fluorometholone) or antibiotics after antibiogram (gentamicin, kanamicin, neomicin, erythromicin, ofloxacin, polymyxin-B, colistin) followed in all Demodex-positive blepharitis patients (n = 41). RESULTS: Demodex was found in 52% (62/139) of patients with chronic blepharitis, as against 20% (3/15) of those with acute blepharitis (statistically significant difference, chi 2-test, alpha = 2.5%) and in 29% of quiet eyes (statistically significantly less, alpha = 2.5%, chi 2-test). Gram-positive cocci were isolated from 79% of 57 Demodex-positive patients with blepharitis and 72% of 68 Demodex-negative patients anaerobes in 39% and 37%, gram-negative rods in 11% and 3% (statistically significant difference for gram-negative rods, alpha = 5%, chi 2-test). Of the patients with Demodex, 25% apparently had no more parasites after mercury ointment, 2% (n = 8) and lindan (n = 5) and 15% after cortisone and antibiotics (n = 13). (The best and statistically very significant results (alpha = 1%) were those obtained with mercury ointment, 2%, and lindan: t-test for connected spot checks). CONCLUSIONS: Gram-positive and gram-negative bacteria grew more often in patients with Demodex. Demodex seems to be a mediator of chronic blepharitis; we recommend that mites be sought in cilia of chronic blepharitis patients. Mercury ointment, 2% and lindan proved efficient for specific therapy, the main problem being the laborious application and toxicity.
[In vivo confocal microscopy in blepharitis].
BACKGROUND: Dysfunction of the meibomian glands with inflammation and obstruction has been suggested to be an important factor in the pathogenesis of chronic blepharitis. Few objective tests are, however, available to examine the meibomian glands directly. PATIENTS AND METHODS: Nineteen patients with anterior blepharitis, meibomitis, meibomian gland dysfunction or severe keratoconjunctivitis sicca associated with blepharitis as well as 10 patients with normal lid margins were examined with the HRTII/RCM in vivo confocal microscope. Scans of the tear film, the tarsal conjunctiva, the hair follicles and the meibomian glands were analysed by a masked observer. RESULTS: Patients with normal lid margins exhibited a minimal round cell infiltrate in the tarsal conjunctival epithelium and largely normal ducts of the meibomian glands lined with a multilayered epithelium as well as normal gland acini. In patients with anterior blepharitis, blepharitis associated with autoimmune peripheral ulcerative keratitis and blepharitis in the context of severe dry eye, confocal microscopy disclosed normal meibomian glands. In 12 patients with blepharitis/meibomitis or meibomian gland dysfunction, profound pathology was visible with dilatation and obstruction of the meibomian gland ducts. In 15 of 19 patients with blepharitis/meibomitis, but not in meibomian gland dysfunction, an intense inflammation was observed in the tarsal conjunctival epithelium and stroma. In one patient, demodex folliculorum was evident in vivo. In patients with normal lid margins as well as in patients with blepharitis, hair follicles appeared within normal limits. CONCLUSIONS: In vivo confocal microscopy allowed the examination of the tear film, the tarsal conjunctiva, the lid margin including the lash follicles and the meibomian glands. In patients with meibomian gland disease pathological changes could be visualised and documented objectively. The presence of an inflammatory infiltrate permitted us to differentiate between meibomitis and meibomian gland dysfunction. Changes of the lash follicles do not seem to play an important role in blepharitis. Thus, in vivo confocal microscopy represents an objective technique in the classification and follow-up of patients with blepharitis.
[Chronic blepharitis and Demodex].
PURPOSE: Demodex is a mite commonly found in eyelash hair follicles and sebaceous glands of healthy people. Due to the fact this mite has also been reported in many chronic cases of blepharitis, we aimed to investigate the incidence of infestation with this mite in healthy people and in patients with chronic blepharitis, in addition to evaluating the response to the different treatments used for blepharitis. METHODS: 105 subjects without blepharitis were selected as a control group and 20 subjects diagnosed as having chronic blepharitis were selected as patients. Epilated eyelashes were observed under microscope in both groups of patients. Those with overpopulation of mites were treated with ether lid and eyelash scrubs and 2% mercury oxide ointment. RESULTS: The incidence of Demodex infestation in the control group was 0.08 mites per eyelash, whereas in the patients with chronic blepharitis the incidence was 0.69 mites per eyelash; this difference was statistically significant (p=0.006). All the mites found were Demodex folliculorum except in one patient where the mite was identified as Demodex brevis. After 3-8 weeks of specific treatment the number of mites per eyelash decreased dramatically (0.03, with p=0.001). Two patients were intolerant of the therapy. CONCLUSIONS: In this study the incidence of Demodex in patients with blepharitis was very high, when compared with normal subjects, showing a clear association between blepharitis and Demodex infestation. Treatment with mercury oxide ointment was satisfactory in controlling the infection, despite difficulty in its application and occasional toxicity.
Tear lysozyme measurements in chronic blepharitis.
Tear lysozyme concentrations were measured on 47 patients with chronic blepharitis and 22 normal control patients. The patients consisted of 26 individuals with various types of chronic blepharitis alone and 21 individuals with chronic blepharitis and clinically-diagnosed keratoconjunctivitis sicca (KCS). The mean lysozyme concentration of blepharitis patients without KCS (4070 micrograms/ml) was not significantly different from normals (3760 micrograms/ml). However, mean lysozyme concentration of the blepharitis patients with KCS (2530 micrograms/ml) was significantly lower than normals or blepharitis patients without KCS (p less than 0.01). It was concluded that tear lysozyme deficiency does not play a significant role in the etiology of chronic blepharitis. However, a large percentage of patients with chronic blepharitis were found to have KCS.
Ulcerative blepharitis in atopic patients--is Candida species the causative agent?
A total of 50 patients suffering both from atopic skin disease and different clinical forms of blepharitis have been included in this study. Microbiological investigations (for bacteria and fungi) of the lid margins were performed in all cases. In 21 (42%) of the patients an ulcerative blepharitis which heavily involved the follicles of the lashes was diagnosed. The remaining 29 cases presented with blepharitis of the squamous type. The cultures revealed that 19 of the 21 patients with ulcerative blepharitis were found to grow Candida species, whereas fungi could not be detected in any of the other cases of blepharitis. The frequencies of concomitant bacterial organisms found in the cultures were similar in both groups. As atopic patients are known to exhibit a defect in their cell-mediated immunity and possibly also a defective IgA antibody response it is a widely accepted assumption that these immunological changes are contributing factors to the development of a localised inflammation of the lids which is initiated by a variety of micro-organisms. We postulate that when Candida species happen to coincide with severe inflammation in atopic patients a blepharitis of the ulcerative type will develop or deteriorate thereby implying that these microorganisms may play an important role in the development or deterioration of this severe chronic inflammation. It is therefore advisable to perform repeated scrapings and cultures in every case of recalcitrant blepharitis.
Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis.
Change in the expression of body fluid proteins is caused by many diseases or environmental disturbances. The changes in tear proteins are also associated with various pathological eye conditions. Especially, chronic blepharitis is one of the most common conditions seen in the ophthalmologist's office. However, there are no specific clinical diagnostic tests for blepharitis, and it is difficult to treat effectively. Therefore, the aim of this study was to screen prognostic or diagnostic marker tear proteins for blepharitis and investigate pathogenesis of this disease using proteomics techniques. The tear proteins expressed in patients suffering from blepharitis (patient, n=19) and healthy volunteers (control, n=27) were analyzed using the two-dimensional electrophoresis (2-DE) technique. The differentially expressed proteins in patients were identified with ESI-Q-TOF (electrospray-quadrupole-time-of-flight) mass spectrometry and confirmed with western blotting. Nine proteins in patient were down regulated about 50% compared to those of the control: serum albumin precursor, alpha-1 antitrypsin, lacritin precursor, lysozyme, Ig-kappa chain VIII, prolactin inducible protein (PIP/GCDFP-15), cystatin-SA III, pyruvate kinase, and an unnamed protein. The use of the two-dimensional eletrophoretic technique could give more insight into the disease-related protein expression changes in tear fluids. Our findings reveal that the composition of tear proteins in blepharitis patients is different from that of healthy subjects and may provide further insights into the pathogenesis of blepharitis.
Meibomian gland dysfunction in chronic blepharitis.
We examined 57 patients with symptoms of chronic blepharitis using meibomian gland expression, meibography, tear osmolarity, and the Schirmer's test. We also performed meibography on 20 normal patients free of chronic blepharitis. We found that 42 blepharitis patients (74%) had evidence of meibomian gland loss, whereas only four of 20 normal patients (20%) had any gland dropout. We performed cluster analysis on the data from the patients with blepharitis and found that these patients tended to fall into distinct groups with clinically relevant characteristics. We also found that tear osmolarity correlated positively with gland dropout (+0.413) and negatively with excreta volume (-0.499). This study demonstrates that an objective analysis of meibomian gland function may be used to assess chronic blepharitis and define subsets of blepharitis with measurable differences. It also supports the significance of meibomian gland dysfunction on tear osmolarity and the evaporative state of the eye.
Quantitative evaluation of atopic blepharitis by scoring of eyelid conditions and measuring the water content of the skin and evaporation from the eyelid surface.
PURPOSE: To quantitatively evaluate the condition of the eyelid skin of patients with atopic blepharitis, their symptoms were scored and the water content of the skin and evaporation from the skin were measured. METHODS: Forty patients with atopic blepharitis were examined. The condition of eyelid skin (erythema, edema/papulation/oozing/crust, excoriation/lichenification) was scored from 0 to 3 points. Water content and water evaporation were measured with a Moisture Checker and an evaporimeter, respectively. Eleven age-matched volunteers without atopic disorders were recruited as normal controls. RESULTS: The Moisture Checker values and water evaporation from lid skin were significantly correlated (r = -0.44, p = 0.006). The Moisture Checker values of the patients with atopic blepharitis was 35.5+/-8.2% (44.7 +/-10.6% in the normal controls, p = 0.009), and water evaporation from their lid skin was 3.6+/-0.9 g/cm2 per second (2.0+/-0.3 g/cm2 per second, p < 0.001); then, the patients were divided into four groups, from "asymptomatic" to "severe," according to the sum of their blepharitis scores. Patients with lower blepharitis scores tended to have higher Moisture Checker values and lower water evaporation values. CONCLUSION: Scoring of eyelid condition enabled us to objectively estimate the severity of atopic blepharitis. Measurements of the water content of lid skin and water evaporation from lid skin are useful in evaluation of the severity of this disease.
The effect of Staphylococcus aureus phage lysate vaccine on a rabbit model of staphylococcal blepharitis, phlyctenulosis, and catarrhal infiltrates.
PURPOSE: To evaluate the effect of Staphylococcus aureus phage lysate (SPL) vaccination on the development of blepharitis, corneal phlyctenules, and catarrhal infiltrates and on the development of antibodies and the delayed-type hypersensitivity response to S. aureus. METHODS: Eighty rabbits received an intradermal immunization of cell wall-complete Freund's adjuvant followed by a booster immunization. Rabbits were given topical applications of viable S. aureus in both eyes and 40 rabbits received subcutaneous SPL vaccinations. Clinical observations were made weekly. An enzyme-linked immunosorbent assay was used to measure IgG, IgA, and IgM antibody levels to ribitol teichoic acid in sera, corneas, and tears. The delayed-type hypersensitivity response was evaluated by skin testing after subcutaneous injection of staphylococcal antigens. RESULTS: In the SPL-vaccinated group, phlyctenules developed in eight of 40 rabbits while blepharitis developed in 13 of 40. In the nonvaccinated group, phlyctenules developed in three of 40 rabbits and blepharitis developed in five of 40. The number of rabbits with blepharitis was significantly higher in the SPL-vaccinated group than in the nonvaccinated group. In general, the antibody response to ribitol teichoic acid was enhanced, while the delayed-type hypersensitivity response to S. aureus was depressed. CONCLUSIONS: Vaccination with SPL was not found to have a beneficial effect on the development of blepharitis, phlyctenules, and catarrhal infiltrates in our rabbit model.
[Malassezia fungal blepharitis: a case report].
PURPOSE: Blepharitis is a very common disorder but the role of certain mycoses in the etiopathogenesis of blepharitis remains controversial. OBSERVATION: We report the case of a 29-year-old man presenting with bilateral redness and intense itching of the edge of the eyelid. Slit-lamp examination showed vasodilation of the vessels of the edge of the eyelid associated with seborrhea and a sticky yellowish substance at the roots of the eyelashes. When the substance dried and fell, microulcerations were seen at the base of the eyelids, characteristic of follicular-seborrheic blepharitis. Otherwise the ophthalmological examination was normal. Treatment with eye drops (antibiotics, antiseptics, corticoids, antihistamines) was tried several times. The blepharoconjunctivitis regressed during these treatments without totally disappearing, recurring after the treatment was discontinued. Bacteriological and fungal exams were conducted, showing numerous Malassezia furfur spores and hyphae. Given that there was no antifungal eye drop preparation on the market, topical ketoconazole (Nizoral) was prescribed. Two weeks later, the condition had cleared, with no recurrence after 5 months of follow-up. DISCUSSION: Malassezia is a saprophyte species that may play a role in certain cases of chronic blepharitis, either through a reaction of intolerance and hypersensitivity or occasional proliferation. Treatment consists in eradicating the causal fungus using an antifungal agent associated with symptomatic treatment. We stress that fungal exams should be conducted whenever blepharitis recurs.
The Prevalence of Demodex folliculorum in blepharitis patients and the normal population.
PURPOSE: Demodex folliculorum (DF), which is frequently found in patients with chronic blepharitis, is a well-known common inhabitant of eyelash follicles. In the present study, the prevalence of DF in seborrheic blepharitis patients and controls was investigated. In addition, the associations between the presence of DF and host factors (age, sex) were analyzed. METHODS: A prospective, cross-sectional study was done involving 500 cases. In all, 6000 cilia from 170 patients with seborrheic blepharitis and 330 patients with normal eyes were examined for DF. Twelve eyelash samples were epilated from each patient and examined under the light microscope. RESULTS: DF was found in 28.8% (49/170) of patients with blepharitis and in 26.7% (88/330) of controls. The difference between the two groups was not statistically significant. The overall prevalence was 27.4% (137/500) in all patients. Although the prevalence of DF increased with increasing age, no significant difference was found between the age groups. There was also no statistically significant difference for DF prevalence between males (28.9%; 71/246) and females (24.1%; 61/254). CONCLUSION: Our findings show a high DF prevalence in both blepharitis and control patients and no relationship was found between the presence of DF and host factors (age, sex).
Slime production by coagulase-negative staphylococci isolated in chronic blepharitis.
BACKGROUND: The purpose of the study was to determine the impact of slime-producing strains of coagulase-negative staphylococci (CNS) on non-ulcerative blepharitis. Formerly considered harmless organisms, CNS are now recognised as opportunistic pathogens. Although these microorganisms are a component of normal conjunctival flora, they often produce the typical signs and symptoms of chronic staphylococcal blepharoconjunctivitis. Certain strains produce a polysaccharide extracellular material called "slime". Slime production is considered to be associated with the virulence of the organism. METHODS: Swabs were taken from the lids of 38 eyes of 19 patients with chronic non-ulcerative blepharitis and cultured for CNS. A group of 42 normal control eyes were similarly sampled. The strains of CNS isolated from 26 eyes (68.4%) of the patients with blepharitis and 25 eyes (59.5%) of the normal subjects were studied for slime layer production. RESULTS: No significant difference was found between normal subjects and patients in the incidence of slime producing CNS strains from the conjunctiva. The antibiotic sensitivity profiles of the slime-producing strains were no different from the slime-negative isolates in the blepharitis (p=0.85) and normal group (p=0.25). CONCLUSIONS: Our data suggest that slime production by CNS does not play a significant role in the pathogenesis of staphylococcal blepharitis.
Influence of topical anesthesia on tests diagnostic of blepharitis-associated dry eye syndrome.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Performing diagnostic tests after topical anesthesia instillation could be useful in detecting dry eye associated with blepharitis.
Enhanced secretory group II PLA2 activity in the tears of chronic blepharitis patients.
PURPOSE: Phospholipase A2 (PLA2) hydrolyzes phospholipids, one of the important constituents of human meibomian gland secretions. This study was performed to investigate PLA2 type and activity in the tears of chronic blepharitis patients compared to those of normal persons. METHODS: Tear samples of 36 patients and 10 normal persons were collected in non-heparinized microcapillary tubes. PLA2 activity in the tears was measured by Dole's method, and the results of the blepharitis patients were compared to those of the normal persons. The characterization of PLA2 was performed by the head group preference test and the dithiothreitol (DTT) sensitivity test. The classification of PLA2 type was done using Western blot analysis with anti-human secretory PLA2 antibody. RESULTS: No statistically significant differences were found among the six categories of chronic blepharitis. However, the mean PLA2 activity in the tears of the chronic blepharitis patients was about two times higher than that of the normal controls with statistical significance (P < 0.05). The PLA2 substrate specificity test revealed group II PLA2 activity. Furthermore, the group II PLA2 was identified as a 14 kDa band in Western blot analysis using an antibody raised against human secretory group II PLA2. CONCLUSIONS: Secretory group II PLA2 activity was significantly enhanced in the tears of the chronic blepharitis patients compared with that of the normal controls. It is suggested that this increased enzymatic activity may decrease the tear film stability through increased hydrolysis of phospholipids.
Lid flora in blepharitis.
The microbiologic evaluations of 332 consecutive patients with the primary diagnosis of chronic blepharitis were reviewed and compared to those of 160 control patients. The most commonly isolated organisms from lids with blepharitis were Staphylococcus epidermidis (95.8%), Propronibacterium acnes (92.8%), Corynebacterium sp. (76.8%), Acinetobacter sp. (11.4%), and Staphylococcus aureus (10.5%). Compared to controls, S. epidermidis (p less than 0.01), P. acnes (p less than 0.02), and Corynebacterium sp. (p less than 0.001) were present significantly more often. S. aureus and the isolation of more than one microbial species were not more common in blepharitis patients. Quantitatively, heavy growth, by total and individual species, was significantly more common in blepharitis patients (total, p less than 0.001; S. epidermidis, p less than 0.001, P. acnes, p less than 0.001). These data demonstrate that patients with blepharitis are more likely to have normal skin bacteria on their lids and in greater quantities than nonblepharitis patients.
Bacterial aspects of chronic blepharitis.
Patients with all forms of chronic blepharitis were thoroughly evaluated. These patients were found to have evidence for a primary bacterial component in the disease process only in the clinical staphylococcal and mixed seborrheic/staphylococcal forms of chronic blepharitis. Evidence was found for a shared common pathway for Staphylococcus aureus, coagulase negative staphylococci, and Propionibacterium acnes to contribute to the disease process. These organisms were found to produce lypolytic exoenzymes including fatty wax esterase, cholesteryl esterase, and triglyceride lipase. Statistically significantly larger numbers of coagulase negative staphylococci were found to produce these enzymes in patients with the various forms of seborrheic blepharitis and meibomian keratoconjunctivitis. Additionally, abnormalities in the free fatty acid component of the meibomian secretions were found in these patients supporting the hypothesis that lypolytic exoenzymes produced by bacteria might alter the meibomian secretion. Even though a primary pathogen is identifiable only in staphylococcal and mixed seborrheic/staphylococcal blepharitis, several different bacteria may contribute to the expression of disease in all other forms of chronic blepharitis.