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The survival and growth of microorganisms in mascara during use.

Over 150 mascaras representing eight popular brands were examined for their susceptibility to microbial contamination during their use by study group members. Additional mascaras from patients with symptoms and clinical findings of long-term blepharitis also were investigated. Early in the study, two brands without preservatives supported reproducing populations of microorganisms, including potential eye pathogens. These products, as currently manufactured, were recalcitrant to microbial attack. Microbes associated with the facial skin and fingers of the study group users were typically isolated from mascaras after use. Initial microorganisms isolated from mascaras were usually transients. Establishment of reproducing populations within the cosmetics appeared related to the number of uses, personal habits of the user, and the formulation of the product. Four patients with staphylococcal blepharitis and cosmetics heavily laden with Staphylococcus epidermidis showed marked clinical improvement when they stopped using the contaminated cosmetics. The application of used eye area makeup prior to and following ocular surgery should be avoided.

Bacillus↗

Clinical evaluation of trimethoprim-containing ophthalmic solutions in humans.

We studied trimethoprim in combination with sulfacetamide and polymyxin B and also in combination with polymyxin B alone (without the sulfacetamide) to determine the efficacy and safety of these new antibiotic combinations in the eyes of patients with bacterial conjunctivitis or blepharitis. Patients were selected for the study if they showed at least three of the following criteria: (1) symptoms of a surface ocular infection; (2) a purulent discharge; (3) a polymorphonuclear neutrophilic response on Giemsa stain; (4) a history of recent exposure to an infected individual; (5) a history of an inadequately treated surface bacterial infection. Trimethoprim-sulfacetamide-polymyxin B and polymyxin B-neomycin-gramicidin (Neosporin, the control) eliminated bacteria from the eyes of patients with conjunctivitis or blepharitis with equal effectiveness. There was no loss of effectiveness when trimethoprim-polymyxin B was compared with trimethoprim-sulfacetamide-polymyxin B, suggesting that the sulfacetamide was not a necessary component. The combination antibiotic containing trimethoprim and polymyxin B appears to be an effective topical antibiotic solution for the treatment of ocular surface infections.

Adolescent↗

Ophthalmologic findings in the Cornelia de Lange Syndrome.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a disorder caused in many patients by a mutation in the NIPBL gene with a dominant pattern of inheritance characterized by mental retardation, prenatal and postnatal growth retardation, upper-limb abnormalities, and characteristic facies. Few data exist concerning the ophthalmic findings in this syndrome. METHODS: One hundred twenty individuals with CdLS underwent ophthalmic examination to ascertain the relative frequencies of oculofacial and ophthalmic abnormalities. RESULTS: We confirmed the frequent findings of synophrys (99%), long lashes (99%), hypertrichosis of the brows (96%), ptosis (44%), epiphora (22%), nasolacrimal duct obstruction (16%), blepharitis (25%), and myopia (58%). In addition, we found peripapillary pigment (83%), and microcornea (21%), which have infrequently been mentioned in the literature. CONCLUSION: Patients with CdLS can have multiple eye problems. Many of these problems can be readily treated, including myopia, blepharitis, nasolacrimal duct obstruction, and ptosis. Early examination is recommended for all children known or suspected to have CdLS.

Adolescent↗

[Tear-film deficiencies in patients with sarcoidosis; clinical study of 56 patients].

BACKGROUND: The eye and its adnexa are frequently involved in sarcoidosis. Keratoconjunctivitis sicca is a typical manifestation that is believed to result from aqueous-layer deficiency in context with lacrimal gland disease. In this study we determined which layer of the tear-film might be involved. PATIENTS AND METHODS: Fifty-six patients with clinically and histologically proven sarcoidosis were prospectively analysed for symptoms of dry eye, visual acuity, signs of blepharitis, Schirmer II test, rose bengal test, fluorescein staining, break-up time (BUT), and impression cytology (IPC). Deficiencies of the lipid, water and mucin layers were differentiated. The observations were compared with those from a control group of patients with symptoms of "dry eye" (n = 56). RESULTS: All patients in the control group, but only 20 sarcoidosis patients had dry eye symptoms. The BUT in the control group (7.2 +/- 5.4; mean +/- SEM) was shorter (p < 0.02) than in sarcoidosis patients (8.9 +/- 4.5; mean +/- SEM). Compared with the sarcoidosis patients, conjunctivitis occurred more frequently in the control group (p < 0.01). Rose bengal staining was positive in 18 sarcoidosis patients, and in 35 patients of the control group (p < 0.01). Signs of blepharitis, the results of Schirmer test, fluorescein staining and IPC, and the frequent incidence of deficiencies of aqueous layer, lipid layer and combined deficiencies of two or more layers did not differ significantly between the two groups. Deficiencies of the mucin layer were detected in 43 sarcoidosis patients, and in 51 patients in the control group (p < 0.05). CONCLUSIONS: Tear-film deficiencies are common in sarcoidosis patients, even when clinical symptoms are absent. Observations herein suggest that patients with sarcoidosis may not only suffer from deficiencies of the aqueous layer, but also of the mucin and lipid layers.

Adult↗

[Demodex folliculorum].

The author reports on Demodex folliculorum ("hair follicle mite"), a frequent and widespread parasite. These mites are found in hair follicles of eyelashes in particular. In ophthalmology they are responsible for chronic eczematous blepharitis ("blepharitis acarica") with trichiasis and madarosis. Therapy is unsatisfactory. The author has now discovered that isoptocarbachol 3% eyedrops successfully combat Demodex folliculorum. The solution was first tested experimentally on house flies (Musca domestica) and was later used to treat patients affected with the parasite: a cotton bud impregnated with this parasympathomimetic (anticholinesterase) drug was applied to the border of the eyelids several times.

Adult↗

Meibomianitis: polar lipid abnormalities.

PURPOSE: To determine abnormal meibomian gland secretion polar lipids from meibomianitis patients and to determine the significance of these lipid differences. METHODS: Meibomian gland secretions were collected from controls and patients with chronic blepharitis. These meibomian gland lipids (meibum) were first separated by thin-layer chromatography. Polar lipids were then separated utilizing high-pressure liquid chromatography with ultraviolet detection. Individual peaks were identified by comparison to standards and retention time. RESULTS: A polar lipid with an HPLC retention time longer than either phosphatidylcholine or sphingomyelin and shorter than phosphatidylethanolamine was significantly greater in the meibomianitis group (P<0.05) compared with other chronic blepharitis groups and normals. This polar lipid's retention time was similar to that of dimethylphosphatidylcholine or possibly lysophosphatidylcholine. Additionally, meibomianitis polar lipids' normal fatty acids were highly unsaturated and differed from those of other groups, none of which were unsaturated. CONCLUSION: Many of the most significant differences in meibomianitis meibum composition occur in the polar lipids rather than the nonpolar lipids. Further investigations will determine the true significance of these findings.

Blepharitis↗

Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of meibomian gland dysfunction.

OBJECTIVE: To investigate the efficacy of topical cyclosporine A 0.05% (tCsA) (Restasis, Allergan Pharmaceuticals) in the treatment of meibomian gland dysfunction (posterior blepharitis). METHODS: Thirty-three patients with symptomatic meibomian gland dysfunction were randomized in a prospective study to either tCsA or placebo (Refresh Plus preservative-free artificial tears), 2 times daily for 3 months. They were evaluated at baseline and at 1, 2, and 3 months for subjective symptoms and objective signs including meibomian gland inclusions, lid margin vascular injection, tarsal telangiectasis, fluorescein staining, tear breakup time, and Schirmer scores. RESULTS: Twenty-six patients completed the study. All patients were tested for ocular symptoms, lid margin vascularity, tarsal telangiectasis, meibomian gland inclusions, tear breakup time, and fluorescein staining. At the 3-month visit, the tCsA group showed a greater improvement in ocular symptoms than the placebo group, but this difference was not statistically significant. At the 3-month visit, several objective examination findings were statistically significantly (P < 0.05) improved in the tCsA group compared with the placebo group. These differences included lid margin vascular injection, tarsal telangiectasis, and fluorescein staining. The most significant finding (P = 0.001) was the greater decrease in the number of meibomian gland inclusions in the tCsA group compared with the placebo group. CONCLUSIONS: Topical CsA may be helpful in the treatment of meibomian gland dysfunction (posterior blepharitis). Topical CsA did not induce an improvement in the symptoms, but it did decrease the number of meibomian gland inclusions in patients with meibomian gland dysfunction.

Adult↗

Effect of 0.03% tacrolimus ointment on conjunctival cytology in patients with severe atopic blepharoconjunctivitis: a retrospective study.

PURPOSE: To evaluate the efficacy and effect of tacrolimus ointment on conjunctival cytology in patients with atopic blepharoconjunctivitis or keratoconjunctivitis. METHODS: Ten patients with severe atopic blepharoconjunctivitis treated with 0.03% tacrolimus ointment once daily as an intermittent treatment were analysed retrospectively. The main outcome measures were clinical response to topical tacrolimus, adverse events and changes in the inflammatory cells obtained from conjunctival brush samples. RESULTS: Marked clinical responses in blepharitis and conjunctivitis symptoms were seen after a mean follow-up time of 6 weeks. Clinical scores decreased by 67% in blepharitis and 74% in conjunctivitis symptoms. No severe adverse events or signs of immunosuppression such as herpes simplex infections occurred. No significant changes occurred in visual acuity, refraction, anterior chamber, retina or intraocular pressure. Median decreases were 85% (p =0.01) in conjunctival eosinophils, 50% (p = 0.01) in neutrophils and 58% (p = 0.02) in lymphocytes. CONCLUSIONS: Tacrolimus ointment is potentially a safe and effective treatment for atopic blepharoconjunctivitis. Regular treatment of the eyelids once daily may also lead to clinical and cytological improvement of the conjunctivitis.

Adult↗

Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease.

The ribonucleotide reductase (RR) of herpes simplex virus type 1 (HSV-1) is an important virulence factor, being required for neurovirulence, ocular virulence, and reactivation from latency. The RR activity requires the association of two distinct homodimeric subunits, and the association of the subunits is inhibited in the presence of a peptide homologous to the carboxy terminus of the small subunit. A structural analog of the inhibitory peptide (BILD 1263) has been shown to inhibit the replication of HSV-1 at micromolar concentrations in vitro. We used a mouse model of HSV-1 ocular infection to determine the in vivo efficacy of topical BILD 1263. Treatment of HSV-1 KOS-infected mice resulted in significant reductions in the severity and incidence of stromal keratitis and corneal neovascularization. At higher concentrations (5%) BILD 1263 reduced the severity but not the incidence of blepharitis. Treatment with 5% BILD 1263 also reduced viral shedding from the cornea by 10- to 14-fold (P < 0.001). In uninfected mice treated with 5% BILD 1263, we found no evidence of corneal epithelial damage, conjunctivitis, or blepharitis, and histopathological studies revealed no changes in the corneas of these mice. These results show that the peptidomimetic RR inhibitor BILD 1263 is effective in preventing disease, has an antiviral effect in vivo, and has little or no toxicity.

Animals↗

Herpes simplex virus virion host shutoff (vhs) activity alters periocular disease in mice.

During lytic infection, the virion host shutoff (vhs) protein of herpes simplex virus (HSV) mediates the rapid degradation of RNA and shutoff of host protein synthesis. In mice, HSV type 1 (HSV-1) mutants lacking vhs activity are profoundly attenuated. HSV-2 has significantly higher vhs activity than HSV-1, eliciting a faster and more complete shutoff. To examine further the role of vhs activity in pathogenesis, we generated an intertypic recombinant virus (KOSV2) in which the vhs open reading frame of HSV-1 strain KOS was replaced with that of HSV-2 strain 333. KOSV2 and a marker-rescued virus, KOSV2R, were characterized in cell culture and tested in an in vivo mouse eye model of latency and pathogenesis. The RNA degradation kinetics of KOSV2 was identical to that of HSV-2 333, and both showed vhs activity significantly higher than that of KOS. This demonstrated that the fast vhs-mediated degradation phenotype of 333 had been conferred upon KOS. The growth of KOSV2 was comparable to that of KOS, 333, and KOSV2R in cell culture, murine corneas, and trigeminal ganglia and had a reactivation frequency similar to those of KOS and KOSV2R from explanted latently infected trigeminal ganglia. There was, however, significantly reduced blepharitis and viral replication within the periocular skin of KOSV2-infected mice compared to mice infected with either KOS or KOSV2R. Taken together, these data demonstrate that heightened vhs activity, in the context of HSV-1 infection, leads to increased viral clearance from the skin of mice and that the replication of virus in the skin is a determining factor for blepharitis. These data also suggest a role for vhs in modulating host responses to HSV infection.

Animals↗

Blepharokeratoconjunctivitis in children: diagnosis and treatment.

AIM: Blepharokeratoconjunctivitis (BKC) is a poorly described entity in children. This study characterises this syndrome in childhood and evaluates epidemiology, clinical grading, and treatment strategies. METHODS: 44 children (20 white, 22 Asian, 2 Middle Eastern, median age 5.4 (range 1-14) years) with a diagnosis of BKC were followed for a median of 7 years. Diagnostic criteria included recurrent episodes of chronic red eye, watering, photophobia, blepharitis including recurrent styes or meibomian cysts, and a keratitis. Clinical features were graded as mild, moderate, or severe. The lids and conjunctiva were cultured. The treatment regimen incorporated lid hygiene, topical and/or systemic antibiotics, and topical corticosteroids. RESULTS: The disease was most severe in the Asian and Middle Eastern children (p <0.001), who had a statistically higher risk of subepithelial punctate keratitis (p = 0.008), corneal vascularisation (p <0.001), and marginal corneal ulcerations (p = 0.003), than the white group. 15 children had culture positive lid swabs. Most children had a reduction in symptoms and signs with treatment, and progression of disease after the age of 8 was rare. CONCLUSIONS: BKC in children can be defined as "a syndrome usually associated with anterior or posterior lid margin blepharitis, accompanied by episodes of conjunctivitis, and a keratopathy including punctate erosions, punctate keratitis, phlyctenules, marginal keratitis, and ulceration." BKC is common in children in a tertiary referral corneal and external diseases clinic, with the more severe manifestations in the Asian and Middle Eastern populations. Therapy is effective and loss of sight can be prevented in most cases.

Adolescent↗

Identification and antibiotic susceptibility of coagulase negative staphylococci isolated in corneal/external infections.

AIMS: To identify and determine antibiotic susceptibility of coagulase negative staphylococci (CoNS) isolated from patients with chronic blepharitis, purulent conjunctivitis, and suppurative keratitis. METHODS: A retrospective review of all culture positive cases of chronic blepharitis, purulent conjunctivitis, and suppurative keratitis between July 1995 and December 1996 was performed. Cases in which CoNS were the sole isolates were analysed. Species identification was performed by using a commercially available standardised biochemical test system. Antibiotic susceptibility to penicillin, gentamicin, tetracycline, erythromycin, ciprofloxacin, and teicoplanin was determined by agar disc diffusion (Kirby-Bauer method). Teicoplanin resistance was confirmed by agar dilution. RESULTS: 42 Staphylococcus epidermidis, four S warneri, three S capitis, two S hominis, one each of S xylosus, S simulans, S equorum, and S lugdunensis were identified. 37 CoNS were penicillin resistant, 12 gentamicin resistant, 28 tetracycline resistant, 18 erythromycin resistant, four ciprofloxacin resistant, and one teicoplanin resistant (MIC, 32 microg/ml). In total, 16 strains were resistant to three or more antibiotics. CONCLUSION: Species of CoNS apart from S epidermidis may be isolated from patients with corneal and external infection. Antibiotic susceptibility of CoNS is unpredictable and multiresistant strains are common. As a result, antibiotic susceptibility testing should be performed in all cases of clinically significant ocular infections caused by CoNS.

Anti-Bacterial Agents↗

Improved protection from primary ocular HSV-1 infection and establishment of latency using multigenic DNA vaccines.

PURPOSE: To compare the effectiveness of immunization with "naked" DNA corresponding to the genes encoding five HSV-1 glycoproteins, gB, gC, gD, gE, and gI (5gP DNA), with immunization with the five glycoproteins (5gP protein). Also, to compare immunization of 5gP protein in Montanide ISA 720 (SEPPIC, Paris, France), an adjuvant recently approved for use in humans, with immunization of 5gP protein in Freund's adjuvant. METHODS: BALB/c mice were vaccinated with 5gP DNA or 5gP protein emulsified in ISA 720 or Freund's adjuvant. Neutralizing antibody titers were determined by plaque-reduction assays. IL-2, -4, and -12 and IFN-gamma levels were determined by ELISA after in vitro stimulation of spleen cells. After ocular challenge with 2 x 10(5) plaque-forming units [pfu] per eye of HSV-1 strain McKrae, virus replication in the eye, survival, blepharitis, corneal scarring, and latency were determined. RESULTS: Neutralizing antibody titers (approximately 1:800-1:1200), corneal scarring (trace) and survival (100%) were similar for all vaccine groups, including 5gP DNA. Compared with the other vaccine groups, the 5gP DNA group had less ocular virus replication, as judged both by maximum virus titer and time of viral clearance. ISA 720 appeared more effective than Freund's against ocular virus replication and eye disease. The 5gP DNA-vaccinated mice had less blepharitis and latency than any other group and had the highest levels of IL-12 and IFN-gamma. All vaccine groups had similar levels of IL-2. CONCLUSIONS: The 5gP DNA vaccine appeared to be more effective than the corresponding protein subunit vaccine, regardless of adjuvant. Emulsification of the 5gP protein in ISA 720 appeared to be more effective than emulsification in Freund's adjuvant.

Animals↗

Toxicological study on rats fed haloperidol: 80 week chronic toxicity test.

Haloperidol (HPL) was administered by presenting HPL-admixed food to 20 male and 19 female Sprague-Dawley rats from the age of 5 weeks at a target dose of 1.0 mg/kg/day for 80 weeks. The range of the actual daily dose was 0.48-1.11 mg/kg in males and 0.34-0.73 mg/kg in females. The control rats(13 males and 13 females) were given normal food. In the present study, the general condition and locomotor activity of these rats were examined. 1. The number of HPL-treated animals that died during the administration periods (11 males and 9 females) and the symptoms observed immediately before their death were comparable to those in the control group. Vacuous chewing movement developed in HPL-treated animals (12 males and 11 females) after the 28th week of administration. These movements showed a tendency of decrease after the 68th week. Blepharitis was observed in all females and 3 males of the HPL-treated group, but in none of the controls of either sex. Subcutaneous masses in the chest and abdomen were observed in 3 HPL-treated females and 6 control females, but there was no significant difference in their incidence between the two groups. 2. The body weight gain in the HPL-treated group was suppressed in males, but was promoted and then suppressed in females. The food consumption in the HPL-treated group was similar, but the water consumption was reduced in both sexes as compared with the control groups. 3. Locomotor activity was reduced in the HPL-treated group for both males and females, and no tolerance developed. These results suggest that HPL does not have a possibility to cause death even by chronic administration at the doses examined in the present study. However, the occurrence of body weight losses and blepharitis indicated the need for particular attention to these symptoms during chronic administration.

Animals↗

Why the eye becomes dry: a cornea and lacrimal gland feedback model.

PURPOSE: Many explanations have been offered for why a large segment of the population develops dry eye. The purpose of this paper is to describe a new unifying theory of dry eye that incorporates all of these causes. METHODS: Data from the Department of Ophthalmology, University of Iowa Hospitals and Clinics was analyzed from 520 patients with dry eye, blepharitis and other conditions to assess the relationship between dry eye and blepharitis. This data was reviewed in terms of the relationship between dry eye, menopause, and aging. Also examined in detail were many of the proposed causes for dry eye in the literature. RESULTS: A close relationship between corneal damage and lacrimal gland function is hypothesized. Not only does decreased lacrimal gland output damage the ocular surface, but also damage to the corneal surface creates a negative feedback loop and damage to the lacrimal gland. There are probably several mechanisms by which this feedback occurs. One mechanism results from interruption or damage to the sensory corneal nerves. Damage to the nerves within the lacrimal gland may be another mechanism. Alteration of growth factor levels in the lacrimal gland, which occurs following corneal damage, represents another possible mechanism. Contact lenses and corneal refractive surgery are additional elements that may create negative feedback to the lacrimal gland. CONCLUSION: The ocular surface and the lacrimal gland functions as a tightly integrated unit. Dry eye conditions damage the ocular surface and this in turn leads to further damage to the lacrimal gland.

Age Factors↗

[Treatment of acne rosacea with 13-cis-retinoic acid].

13 patients of both sexes, affected by a severe form of papular rosacea, were treated with 13-cis retinoic acid (1 mg/kg/day) for 2 months. One patient interrupted the treatment after 15 days because of severe blepharitis. The size and number of papules were progressively reduced from the 2nd week, reaching complete regression at the 6th week. Three patients complained of mild blepharitis, 9 patients developed dry cheilitis.

Adult↗

A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing.

Previous studies to determine the efficacy of new antiviral compounds in treating HSV ocular infections have used rabbit models. However, rabbits are expensive to purchase and maintain, and require the use of substantial amounts of test compounds. We have used the currently licensed antiviral trifluorothymidine in a murine model of HSV-induced ocular infection to demonstrate that the less expensive murine model can be used for the in vivo evaluation of potentially useful antiviral compounds. Treatment with TFT reduced the severity of blepharitis, vascularization of the cornea, stromal keratitis, and the percentage of animals developing symptoms. TFT treatment did not reduce the peak titers of infectious virus in the eyes of the infected animals, but did enhance clearance of virus from the tissues in a dose-dependent manner. Treatment with 1.0% TFT prevented the establishment of reactivatable latent infections. However, treatment with 0.01% or 0.1% TFT did not affect latency. The ED50 values for blepharitis, vascularization, and stromal keratitis ranged between 0.007% and 0.023%. These results are very similar to results obtained in rabbits and establish baseline data for comparing rabbit and murine models. This murine model provides a potentially less expensive alternative for in vivo drug testing.

Animals↗

Ocular evaporation in meibomian gland dysfunction and dry eye.

BACKGROUND: Secretions from the meibomian gland are believed to be important in reducing ocular surface water evaporation and preventing dry eye. Patients with blepharitis frequently have meibomian gland dysfunction with loss of meibomian glands (drop out). The authors hypothesized that dry eye that often occurs in patients with chronic blepharitis is secondary to increased evaporation associated with gland loss. METHODS: The authors measured the ocular surface water evaporation and tear osmolarity of patients with meibomian gland drop out and patients with gland drop out with a low Schirmer test. These findings were compared with those of a control group. RESULTS: The authors found that eyes with meibomian gland drop out and those with drop out and a low Schirmer test had a significantly higher evaporative rate at 30% relative humidity (average, 49.9 +/- 21 x 10(-7) g/cm2/second, or 0.49 +/- 0.29 microliters/minute evaporative loss per eye, and 59.1 +/- 28 x 10(-7) g/cm2/second, or 0.58 +/- 0.23 microliters/minute, respectively) when compared with those in the control group (average, 14.8 +/- 6 x 10(-7) g/cm2/second, or 0.15 +/- 0.07 microliters/minute [P < 0.05]). There was a significant correlation between evaporative rate and gland drop out (r = 0.522). CONCLUSION: Patients with meibomian gland drop out, and especially those with low tear production by Schirmer test, have an increased risk of dry eye developing through increased evaporation.

Adult↗