Calcinosis conjunctivae in chronic blepharitis

We present a case of a 53-year-old female patient with chronic blepharitis and conjunctival overgrowth of the cornea. Histologically the conjunctival overgrowth contained foreign body granulomas around calcification focuses. This could have been promoted by the application of phosphate-containing eye drops and the presence of chemokines like TNF-alpha, which occur in chronic blepharitis. Thus, we recommend the application of phosphate-free eye drops in patients with chronic blepharitis.     

Classification of chronic blepharitis

Since last thoroughly evaluated over three decades ago, the clinical spectrum of chronic blepharitis has changed. The relative prevalence of Staphylococcus aureus alone or in combination with seborrheic blepharitis has decreased. The relative prevalence has increased of seborrheic blepharitis with or without associated excess meibomian secretions (meibomian seborrhea) or inflammation (meibomitis). Primary meibomitis appears not to be a primarily infectious entity but to represent a facet of generalized sebaceous gland dysfunction and to be found in association with seborrheic dermatitis or acne rosacea. The keratoconjunctivitis found in association with primary meibomitis may be contributed to by the production of bacterial lypolytic exoenzymes that split neutral lipids, resulting in an increased level of free fatty acids in the tears. A frequent finding of keratoconjunctivitis sicca in this patient population, especially the S. aureus group (50%), is of note. Of particular importance is that these entities be recognized as chronic diseases requiring control and ones for which there is no "cure."     

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.     

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.     

The role of cholesterol in chronic blepharitis

Chronic blepharitis has been a difficult disease to define either microbiologically or biochemically. Sterols from meibomian secretions of normal subjects and patients were analyzed, and important differences were observed. Based on analyses of these secretions, two significantly different (P less than 0.001) types of normal subjects were found, those with and those without cholesterol esters [Norm(CP) and Norm(CA), respectively]. All patients' secretions contained cholesterol esters. Evidence was obtained which suggests that oxysterols may control the ester cholesterol accumulation. Furthermore, only when cholesterol esters were present did wax and sterol esters containing unsaturated fatty acids accumulate. Over 90% of these unsaturated fatty acids were normal (unbranched); the rest were iso-fatty acids. Preliminary results also suggest that the ester fatty alcohols are much more complex than previously reported; seven alcohols were common to all samples analyzed. Additionally, highly oxygenated alcohols were detected, especially in the meibomian keratoconjunctivitis (MKC) disease group. The MKC samples also contained an alcohol (mass, M/Z 378) not present in any of the other samples analyzed. Based on analysis of variance and linear-regression models, it was determined that the long-chain (C20-28) fatty acids were more important in determining disease signs. Furthermore, in the MKC group, the ratio of unsaturated C18 fatty acids to cholesterol in the wax and sterol esters was significantly different (P less than 0.05) from the Norm(CP) group. The authors discuss the fact that rabbit meibomian secretions are stable, despite containing a very high percentage of ester sterols, and relate this to their high percentage of branched-chain fatty acids and low percentage of unsaturated fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bacterial lipases and chronic blepharitis

Eyelids and conjunctivae of 36 normal individuals and 60 patients from six clinical groups of chronic blepharitis were cultured for aerobic and anaerobic bacteria. The most common species isolated were coagulase-negative staphylococci (C-NS) and Propionibacterium acnes. All strains of these species, and all Staphylococcus aureus strains isolated were tested for the ability to break down triglycerides, cholesterol esters, and fatty waxes. Each strain was incubated independently with appropriate substrates in nutrient media. Each medium was then extracted and assayed for the presence of substrate hydrolysis products by thin-layer chromatography. The percentage of strains capable of hydrolyzing a particular substrate was determined for each individual. S. aureus was a consistent and strong lipase producer, able to hydrolyze all three substrates. P. acnes was able to hydrolyze triolein and behenyl oleate but not cholesteryl oleate. No differences were observed among groups for P. acnes or S. aureus. C-NS showed a high degree of strain variability. Eighty-three percent of C-NS strains could hydrolyze triolein, 82% behenyl oleate, and 40% cholesteryl oleate. Significant group differences were seen in the percentage of lipase positive C-NS strains isolated per individual. Patients in the mixed staphylococcal/seborrheic, meibomian seborrheic, secondary meibomitis, and the meibomian keratoconjunctivitis (MKC) groups harbored significantly more C-NS strains capable of hydrolyzing cholesteryl oleate than did normal individuals. Patients in the meibomian seborrheic, secondary meibomitis, and MKC groups harbored significantly more C-NS strains capable of hydrolyzing behenyl oleate than did normals. No group differences were seen among groups with triolein hydrolyzing C-NS strains.     

Comparative bacteriology of chronic blepharitis.

One hundred and fifteen patients with chronic blepharitis were compared with 47 normal controls. Six clinically distinct groups of blepharitis were observed: staphylococcal; seborrhoeic, alone, with associated staphylococcal superinfection, meibomian seborrhoea, or secondary inflammation of the meibomian glands; and meibomian keratoconjunctivitis (MKC). Staphylococcus aureus was isolated in appreciable frequency from the staphylococcal and the mixed staphylococcal/seborrhoeic groups in contrast to the normal and non-staphylococcal groups. Coagulase-negative Staphylococcus spp., Propionibacterium acnes, and cornyneform bacteria were the most commonly isolated bacteria from the lid for all groups. Cultures of material expressed from the meibomian glands yielded similar organisms but in reduced frequency. Testing of antibiotic susceptibility revealed Staph aureus to be usually sensitive to most commonly used ophthalmic antimicrobials except sulphonamides.     

Demodex as an etiological factor in chronic blepharitis

PURPOSE: To present and account the results of newest experimental and clinical investigations on the role of Demodex folliculorum and Demodex brevis in the etiology of chronic blepharitis. MATERIAL AND METHODS: A review of literature concerning the role of Demodex in the etiology of chronic blepharitis was done. RESULTS: It has been established that: (1) Demodex folliculorum and Demodex brevis occur among humans worldwide. (2) With age the prevalence of eyelids demodicidosis rises. (3) In the course of chronic blepharitis infection of Demodex folliculorum and Demodex brevis is often observed. CONCLUSIONS: Demodex is an etiological factor in chronic blepharitis.     

慢性睑缘炎与蒸发过强性干眼症的临床观察

目的探讨慢性睑缘炎与蒸发过强性干眼的关系。方法选择2002年11月至2003年4月北京同仁眼科中心门诊诊断为慢性睑缘炎患者4l例（82只眼）,其中男性22例、女性19例,观察其外眼情况,进行泪液分泌试验（SchirmerⅠtest,ST）、泪膜破裂时间（BUT）检测、泪液镜分析以及睑板腺分泌物的细菌学和药敏试验。选择同期门诊青光眼、白内障、准分子激光原位角膜磨镶术术前检查的患者30例（60只眼）设为对照组,其中男性16例、女性14例,对其睑板腺分泌物进行细菌培养和药敏试验,并且对比两组细菌种类和药敏情况。结果41例（82只眼）慢性睑缘炎患者中,30只眼（36.6％）ST〈10mm,56只眼（68．3％）BUT〈10s,46只眼（56．1％）泪液镜分级3级以上。两组睑板腺分泌物中培养出表皮葡萄球菌、金黄色葡萄球菌及棒状杆菌。两组细菌阳性率和金黄色葡萄球菌阳性率比较,差异有统计学意义（P〈0.05）。两组表皮葡萄球菌和棒状杆菌药物敏感性比较,差异有统计学意义（P〈0.05）。结论慢性睑缘炎是导致蒸发过强性干眼的重要病因之一。     

The role of wax and sterol ester fatty acids in chronic blepharitis

The authors analyzed the long-chain fatty acids derived from the wax and sterol ester fractions of meibomian secretions from patients with chronic blepharitis and normal individuals. Meibomian secretions were partitioned into separate lipid classes by thin-layer chromatography (TLC). Wax and sterol esters were eluted and transesterified. The liberated fatty acid methyl esters (FAME) were analyzed by gas liquid chromatography. Equivalent chain lengths (ECL) were determined for the 58 peaks found. Thirty-three peaks were positively identified by standards. Peaks were quantified by area normalization. Percentage compositions were computed for each individual and tabulated by group; each fatty acid was analyzed by analysis of variance, and each clinical group was compared with normal subjects. The authors found increases in the series of monounsaturated fatty acids from patient wax/sterol esters compared with normal subjects (P less than 0.05). The authors also found differences in some members of the series of normal, straight, and branched saturated moieties. These differences between normal groups and the blepharitic groups represent a biologically significant pattern that may relate to the disease process. Discriminant analysis provided a 73% probability of correct classification into clinical groups based strictly on FAME analysis (P less than 0.05).     

Tear film flow and stability in herpes simplex keratitis and chronic blepharitis

Tear film flow and stability studies were carried out in patients suffering from herpes simplex keratitis and chronic blepharitis by performing Schirmer test I and tear film break-up-time (BUT) measurements. In herpes simplex keratitis the values of BUT were within normal limits. Values of Schirmer test I were significantly higher (t-test, P less than 0.001) in these patients and are considered to be due to reflex hypersecretion of tears. Schirmer test I was found to be unaffected, whereas the values of BUT seen were significantly lower (t-test, P less than 0.001) in patients suffering from chronic blepharitis. These lower values of BUT can perhaps be attributed to the altered resurfacing of precorneal tear film as a result of changes in the lid margins.     

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.     

Microbial and immunological investigations of chronic non-ulcerative blepharitis and meibomianitis.

Concentrations of tear lysozyme, lactoferrin, ceruloplasmin, IgG, and IgA have been measured by enzyme linked immunosorbent assay (ELISA) in patients with chronic non-ulcerative blepharitis and meibomianitis at the same time as the lid and conjunctivae were cultured for bacteria and fungi by a semiquantitative method. A group of normal controls aged 20 to 80 were similarly sampled, when strains of Staphylococcus epidermidis from their eyes and the patients' eyes were biotyped according to Baird-Parker's scheme. 5% of blepharitis cases had increased numbers of Staph. aureus present on the lids, compared with only a scanty growth obtained from 5% of normals. 7% of blepharitis cases had increased numbers of Staph. epidermidis type VI (coagulase-negative, mannitol-fermenting) present compared with a scanty growth obtained from 6% of normals. Isolation rates of other types of Staph. epidermidis did not differ from those in normals; no types were associated with meibomianitis. Tear protein profiles were normal in most patients, and there was no increase in tear IgA or IgG, which is expected with chronic infection. Overall our evidence suggests that in 88% of cases these lid conditions have an inflammatory aetiology not associated with infection. Staphylococcal isolates often found in the eye usually represent a normal commensal rather than pathogenic flora.     

Severe chronic blepharitis and scarring ectropion associated with discoid lupus erythematosus

Discoid lupus erythematosus is a common form of chronic cutaneous lupus erythematosus, an autoimmune inflammatory disease that affects most of the human organs, including the skin, kidneys, joints, heart and lungs. We describe a 45‐year‐old Caucasian woman with a 21‐year history of eyelid redness and irritation. She had been treated with antibiotics, steroids and eyelid hygiene, a therapy that resulted to brief periods of relief of symptoms. In the last 12 months, her symptoms seemed to have exacerbated, despite the administration of a local therapy. Following biopsy, a diagnosis of discoid lupus erythematosus was confirmed and the patient was placed on a systemic therapy with hydroxychloroquine. The eyelid inflammation decreased but severe scarring of the marginal eyelids persisted, resulting in cicatricial ectropion.     

The role of tetracycline in chronic blepharitis. Inhibition of lipase production in staphylococci

Tetracycline administered in low doses can be effective in the long-term management of patients with meibomian keratoconjunctivitis (MKC). However, the mechanism of action does not appear to be a reduction of bacteria. Seventy-five percent of the ocular staphylococci in such patients are resistant to tetracycline. An alternative mechanism of action could be the inhibition of production of extracellular enzymes by the ocular flora. Inhibition of lipase production could result in lowered levels of toxic hydrolysis products (free fatty acids), which may exacerbate the disease process. The authors tested this hypothesis by examining the differential effect of tetracycline on growth and lipase production in a tetracycline-resistant and tetracycline-sensitive strain of Staphylococcus epidermidis and S. aureus isolated from patients with MKC and Staphylococcal blepharitis. Tetracycline caused significant decreases in the production of lipase in the sensitive and resistant strains of S. epidermidis without concominant decreases in growth. In contrast, S. aureus strains showed parallel decreases in both lipase production and inhibition of growth. The authors propose that the sensitivity of lipase production to tetracycline, in tetracycline-resistant S. epidermidis, may partially explain the clinical improvement observed in MKC patients.     

Analysis of the free fatty acid component of meibomian secretions in chronic blepharitis

Meibomian secretions were collected from 43 patients with chronic blepharitis and 8 normal controls. Patients were divided into six clinically distinct groups of chronic blepharitis. Individual secretions were weighed and separated into specific lipid classes by thin-layer chromatography. The free fatty acid (FFA) fraction was recovered, methylated, and analyzed by gas-liquid chromatography. Quantitation was achieved through the use of an internal standard, and qualitative analyses were aided by the use of commercial external standards. Carbon numbers were expressed in terms of their equivalent chain lengths (E.C.L.). For statistical comparisons, specific acid weights were expressed as nanograms per milligram of secretion. Data from individual subjects were tabulated by group and analyzed by a nonparametric analysis of variance. The FFA portion made up from 0.21% to 1.3% of the total meibomian secretion. Acids ranged in length from 12 to 29 carbon atoms. Iso-branched and anteisobranched carbon chains made up approximately 33% of the FFA fraction. E.C.L.'s corresponding to C16:0, C18:0, and C18:1 together made up a major portion of the total FFA fraction (mean = 49%). When compared to normals, a significantly decreased amount of C12:0 was seen in the mixed seborrheic/staphylococcal group and the meibomian seborrhea group. A significantly decreased amount of anteiso-branched C15:0 was seen in the mixed seborrheic/staphylococcal group. Significantly decreased amounts of anteiso-branched C23:0 were seen in all of the seborrheic blepharitides. A significantly increased amount of isobranched C22:0 was seen in the meibomian keratoconjunctivitis group. No significant differences were seen in the staphylococcal group.