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.

Symptomatic vulvar demodicosis: A case report and review of the literature.

Demodex folliculorum is a mite that commonly inhabits the pilosebaceous units of facial skin, particularly in a perioral and periorbital distribution. While typically an incidental and asymptomatic parasite, Demodex spp. are proposed to contribute to the pathogenesis of facial folliculitis, chronic blepharitis and papulopustular rosacea. Reports of demodicosis in anatomic locations other than the face are exceedingly rare. Here we report a 36-year-old woman with symptomatic Demodex spp. infestation of Fordyce spots of the labia minora. She was referred to dermatology after a 9-month history of tender red bumps on the vulva that would arise and drain over a 24 to 72 hours period, several times per week. Physical examination revealed erythema of the labia minora and introitus with a 4 mm, pink, dome-shaped soft papule on the left labium minus. Wet mount, microbiologic cultures and sexually transmitted infection (STI) screenings were unremarkable. Histopathologic examination revealed a well-circumscribed nodule of suppurative granulomatous inflammation arising in a background of mucosa with Fordyce spots, the majority of which were infiltrated by Demodex spp. Treatment with oral ivermectin and topical metronidazole cream resulted in a symptom-free period of 22 months. This case represents an unusual presentation of symptomatic Demodex infestation.

Blepharitis in dogs: a clinical evaluation in 102 dogs.

BACKGROUND: Blepharitis is a common finding in many dogs with various skin diseases. OBJECTIVES: To establish a definition for canine blepharitis versus periocular dermatitis (POD), to evaluate the clinical findings and underlying skin diseases of blepharitis, and to document the effects of blepharitis on tear production in dogs. ANIMALS: One hundred and two privately owned dogs with clinical signs of blepharitis and a definitive diagnosis of skin disease. METHODS AND MATERIALS: Prospective evaluation of clinical signs and underlying diseases in dogs with blepharitis alone compared to dogs with blepharitis and POD. RESULTS: Brachycephalic dogs were significantly more likely to present with blepharitis than other breeds. Twenty five dogs had blepharitis alone [three dogs (2.9%) without and 22 dogs (21.5%) with cutaneous lesion beyond the periocular skin]. Seventy one of 102 (69%) presented with POD in addition to blepharitis. In six cases a differentiation between blepharitis and POD was not possible. Typical lesions included alopecia/hypotrichosis (97%), erythema (93%), eyelid oedema (50%) and crusts (39.2%). Allergic skin disease (52%) was the most common underlying cause of blepharitis, followed by infectious/parasitic diseases (21.5%), autoimmune disorders (17.7%) and neoplasia (4.9%). Four dogs could not be allocated to any of these disease groups. A diagnosis of parasitism was always accompanied by POD. Reduced tear production was detected in ten of the 53 dogs tested (18.8%). CONCLUSION: Blepharitis occurring in the absence of other skin lesions is rare. The most common underlying cause of blepharitis is allergic dermatitis. Measurement of tear production should be recommended in all cases of blepharitis.

Impact of Eye Cosmetics on the Eye, Adnexa, and Ocular Surface.

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film.

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.

Two cases of tinea ciliaris with blepharitis due to Microsporum audouinii and Trichophyton verrucosum and review of the literature.

Dermatophytes are rarely taken into account among the causes of blepharitis. In our report, we describe a 69-year-old man and a 40-year-old woman with chronic blepharitis for 10 years and 4 years respectively, in whom we examined the scales and pulled eyelashes on direct microscopy and isolated Microsporum audouinii and Trichophyton verrrucosum in the culture. We emphasise that dermatophytes may play a role in the etiopathogenesis of chronic blepharitis. In chronic, treatment resistance blepharitis fungal infections may be considered as possible cause.

Blepharitis and Neoplasms of the Canine Eyelid Margin and Skin.

Canine eyelid masses (tumors) should include the differential clinical diagnoses of neoplasia and blepharitis. They have many common clinical signs including tumor, alopecia, and hyperemia. Biopsy and histologic examination remains the most effective diagnostic test to establish a confirmed diagnosis and appropriate treatment. Neoplasms are typically benign (tarsal gland adenomas, melanocytomas, and so forth) with the exception of lymphosarcoma. Blepharitis is noted in 2 age groups including dogs aged less than 1.5 years and middle aged to older dogs. Most blepharitis cases will respond to specific therapy once an accurate diagnosis is established.

Knockout of Mkp-1 exacerbates colitis in Il-10-deficient mice.

Il-10-deficient mice develop colitis associated with exaggerated Th1/Th17 responses and are a valuable model of inflammatory bowel disease. Mkp-1 is a major negative regulator of MAPKs, and its expression is enhanced by IL-10. To understand the role of Mkp-1 in the regulation of intestinal mucosal immune responses, we studied the effect of Mkp-1 deletion on the pathogenesis of colitis in Il-10(-/-) mice. We found that knockout of Mkp-1 on an Il-10(-/-) background accelerated the development of colitis. Compared with Il-10(-/-) mice, colitis not only appeared earlier but also was more severe in Il-10(-/-)/Mkp-1(-/-) mice. Il-10(-/-) mice exhibited a mild intestinal inflammation in the specific pathogen-free environment, and rectal prolapse rarely appeared before 6 mo of age. In contrast, the majority of Il-10(-/-)/Mkp-1(-/-) mice developed severe colitis rapidly and presented with rectal prolapse after only 2-3 mo. The colon of Il-10(-/-)/Mkp-1(-/-) mice showed diffuse transmural chronic inflammation and mucosal hyperplasia, with significantly more proliferating crypt epithelial cells than those of Il-10(-/-) mice. In addition to the severe colitis, Il-10(-/-)/Mkp-1(-/-) mice also developed conjunctivitis and blepharitis. The colon of Il-10(-/-)/Mkp-1(-/-) mice contained significantly higher levels of proinflammatory cytokines and exhibited greater MAPK activities than did the colon of Il-10(-/-) mice. Splenocytes and lymphocytes from Il-10(-/-)/Mkp-1(-/-) mice produced higher levels of Th1 cytokines ex vivo upon activation than did cells from Il-10(-/-) mice. Our studies support a pivotal role of Mkp-1 as a negative regulator of mucosal immune responses and highlight its protective function against inflammatory bowel disease.

Interventions for chronic blepharitis.

BACKGROUND: Blepharitis, an inflammatory condition associated with itchiness, redness, flaking, and crusting of the eyelids, is a common eye condition that affects both children and adults. It is common in all ethnic groups and across all ages. Although infrequent, blepharitis can lead to permanent alterations to the eyelid margin or vision loss from superficial keratopathy (abnormality of the cornea), corneal neovascularization, and ulceration. Most importantly, blepharitis frequently causes significant ocular symptoms such as burning sensation, irritation, tearing, and red eyes as well as visual problems such as photophobia and blurred vision. The exact etiopathogenesis is unknown, but suspected to be multifactorial, including chronic low-grade infections of the ocular surface with bacteria, infestations with certain parasites such as demodex, and inflammatory skin conditions such as atopy and seborrhea. Blepharitis can be categorized in several different ways. First, categorization is based on the length of disease process: acute or chronic blepharitis. Second, categorization is based on the anatomical location of disease: anterior, or front of the eye (e.g. staphylococcal and seborrheic blepharitis), and posterior, or back of the eye (e.g. meibomian gland dysfunction (MGD)). This review focuses on chronic blepharitis and stratifies anterior and posterior blepharitis. OBJECTIVES: To examine the effectiveness of interventions in the treatment of chronic blepharitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 February 2012. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (CCTs) in which participants were adults aged 16 years or older and clinically diagnosed with chronic blepharitis. We also included trials where participants with chronic blepharitis were a subset of the participants included in the study and data were reported separately for these participants. Interventions within the scope of this review included medical treatment and lid hygiene measures. DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. Data were meta-analyzed for studies comparing similar interventions and reporting comparable outcomes with the same timing. Otherwise, results for included studies were summarized in the text. MAIN RESULTS: There were 34 studies (2169 participants with blepharitis) included in this review: 20 studies (14 RCTs and 6 CCTs) included 1661 participants with anterior or mixed blepharitis and 14 studies (12 RCTs and 2 CCTs) included 508 participants with posterior blepharitis (MGD). Due to the heterogeneity of study characteristics among the included studies, with respect to follow-up periods and types of interventions, comparisons, and condition of participants, our ability to perform meta-analyses was limited. Topical antibiotics were shown to provide some symptomatic relief and were effective in eradicating bacteria from the eyelid margin for anterior blepharitis. Lid hygiene may provide symptomatic relief for anterior and posterior blepharitis. The effectiveness of other treatments for blepharitis, such as topical steroids and oral antibiotics, were inconclusive. AUTHORS' CONCLUSIONS: Despite identifying 34 trials related to treatments for blepharitis, there is no strong evidence for any of the treatments in terms of curing chronic blepharitis. Commercial products are marketed to consumers and prescribed to patients without substantial evidence of effectiveness. Further research is needed to evaluate the effectiveness of such treatments. Any RCT designed for this purpose should separate participants by type of condition (e.g. staphylococcal blepharitis or MGD) in order to minimize imbalances between groups (type I errors) and to achieve statistical power for analyses (prevent type II errors). Medical interventions and commercial products should be compared with conventional lid hygiene measures, such as warm compresses and eyelid margin washing, to determine effectiveness, as well as head-to-head to show comparative effectiveness between treatments. Outcomes of interest should be patient-centered and measured using validated questionnaires or scales. It is important that participants be followed long-term, at least one year, to assess chronic outcomes properly.

Ocular surface discomfort and Demodex: effect of tea tree oil eyelid scrub in Demodex blepharitis.

The purpose of this study was to evaluate the relation between ocular discomfort and ocular Demodex infestation, and therapeutic effects of tea tree oil (TTO) in Demodex blepharitis patients. Three hundred and thirty-five patients with ocular discomfort were evaluated for ocular Demodex infestation and subjective symptoms with ocular surface discomfort index (OSDI) score. Among them, Demodex-infested patients were randomized to receive either eyelid scrubbing with TTO (TTO group,106 patients) or without TTO (Control group, 54 patients) for 1 month. Demodex were found in 84% of patients with ocular discomfort. The number of Demodex was significantly correlated with age (P = 0.04) and OSDI score (P = 0.024). After eyelid scrub treatment, Demodex count was reduced from 4.0 ± 2.5 to 3.2 ± 2.3 in the TTO group (P = 0.004) and from 4.3 ± 2.7 to 4.2 ± 2.5 in the control group (P = 0.27). Also, OSDI score was reduced from 34.5 ± 10.7 to 24.1 ± 11.9 in the TTO group (P = 0.001) and from 35.3 ± 11.6 to 27.5 ± 12.8 in the control group (P = 0.04). In conclusion, Demodex number showed a significant positive correlation with age and subjective ocular discomfort. The tea tree oil eyelid scrub treatment is effective for eliminating ocular Demodex and improving subjective ocular symptoms.

Eyelid margin modification associated with eyelid hygiene in anterior blepharitis and meibomian gland dysfunction.

OBJECTIVE: To assess the changes in eyelid margins associated with eyelid hygiene using Blephaclean eye pads to manage anterior blepharitis or meibomian gland dysfunction (MGD) associated with dry eye complaints. METHOD: The investigation was a bilateral, prospective, interventional, open-label investigation of 3-month duration. The test population included dry eye sufferers with at least mild symptoms (Ocular Surface Disease Index ≥ 13) who presented with mild to moderate anterior blepharitis or MGD. Eyelid hygiene was intensive (twice a day) for the initial 3 weeks and a maintenance regimen (once a day) for the remainder of the study. At each visit, a detailed assessment of eyelid margins was performed. This assessment included the rating of lashes contamination, lid margin foam, droplet, redness and staining, and meibomian gland blockage, dropout, and expression. RESULT: Forty subjects aged 22 to 74 years (54 ± 15 years) were enrolled of whom 39 completed the investigation. The product usage revealed good overall compliance throughout the study. The results revealed a significant improvement in eyelid margin status. Significant (P<0.001) decrease in contamination of eyelashes and meibomian gland blockage were recorded at the completion of the initial 3-week intensive phase and maintained over the 3-month study during the maintenance phase. Meibomian gland expression, indicative of the glands functionality, was also significantly better at the completion of both study phases (intensive P=0.003; maintenance P=0.001). A decrease in eyelid margin staining was also observed but was only significant at the 3-month follow-up at the completion of the maintenance phase. CONCLUSION: The results showed that eyelid hygiene with Blephaclean wipes by subjects with anterior blepharitis or MGD significantly improved the status of the eyelid margin tissues including the meibomian glands. The data confirmed the efficiency of the clinical methodology put forward of 3 weeks of intensive use (twice a day) of eyelid wipes followed by maintenance use (once a day) and that approach achieved a rapid improvement in tissue status and gland patency.

Metagenomic profiling of ocular surface microbiome changes in Demodex blepharitis patients.

Purpose: To compare the ocular surface and meibum microbial communities of humans with Demodex Blepharitis (DB) and healthy controls. Methods: Conjunctival sac and meibum samples from 25 DB patients and 11 healthy controls were analyzed using metagenomic next-generation sequencing (mNGS). Results: The alpha-diversity of the conjunctival sac microbiome of the DB group (observed, Chao1, ACE) was lower than that of the control group, whereas all meibum diversity indicators were similar. In conjunctival samples, the relative abundance (RA) of the phylum Proteobacteria was significantly higher (p=0.023), and the RA of both phyla Actinobacteria and Firmicutes was significantly lower (p=0.002, 0.025, respectively) in the DB group than that in the control group. In meibum samples, the RA of the phyla Proteobacteria and Actinobacteria were similar, whereas that of the phylum Firmicutes was significantly lower in the DB group (p=0.019) than that in the control group. Linear discriminant analysis with effect size measurement of the conjunctival and meibum microbiomes showed that Sphingobium sp. YG1 and Acinetobacter guillouiae were enriched in the DB group. Sphingobium sp. YG1, Acinetobacter guillouiae and Pseudomonas putida in the DB group were related to more severe ocular surface clinical parameters. Discriminative genera's principal coordinate analysis separated all control and DB microbiomes into two distinct clusters. Conclusions: Proteobacteria's increased prevalence may indicate ocular microbial community instability. The species Sphingobium sp. YG1 and Acinetobacter guillouiae are potentially pathogenic bacterial biomarkers in DB. Demodex infection mainly affects the ocular surface microbiome rather than penetrating deeper into the meibomian gland.

Disseminated histoplasmosis with concurrent oral candidiasis in an Eclectus parrot (Eclectus roratus).

Disseminated histoplasmosis caused by Histoplasma capsulatum, a zoonotic fungal organism, is an important disease in animals and humans, particularly those with compromised immune systems. Reports of disseminated histoplasmosis in an avian species are not available within the current literature. Candida albicans, another fungal agent with zoonotic importance, is a commensal of the avian digestive tract that is often associated with opportunistic infections particularly in young or immunocompromised birds. This report describes a case of concomitant histoplasmosis and candidiasis in an Eclectus parrot (Eclectus roratus) characterized by severe granulomatous glossitis, blepharitis and osteomyelitis with numerous intrahistiocytic and extracellular yeasts (H. capsulatum) as well as intralesional hyphae, pseudohyphae and conidia (C. albicans). To our knowledge, co-infection with H. capsulatum and C. albicans has not been reported in an avian species.

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.

Is it always blepharitis? Urbach-Wiethe syndrome (lipoid proteinosis).

A 12-year-old girl presented with recurrent crusty debris and dandruff at the base of both eyelashes despite having completed different medical treatments. She had had a hoarse voice since her early childhood. Upon anterior segment examination of the eyes, we found yellow-white, bead-like papules on the margins of the eyelids. An otolaryngologist detected multiple nodules on the vocal cords and buccal mucosa. Ultrasonography revealed salivary stones in the main parotid ducts. And a dermatological examination revealed thickened skin lesions on the elbows and knees with a biopsy showing histopathological findings of lipoid proteinosis. We diagnosed the patients as having Urbach-Wiethe syndrome or lipoid proteinosis, a rare autosomal recessive multisystem disorder with variable manifestations vary that difficult the diagnosis. The ocular manifestations are not well known among ophthalmologists, but the typical lid lesions are pathognomonic and ophthalmologists should be aware of this presentation to identify patients with Urbach-Wiethe syndrome.