tacrolimus and Blepharitis

Atopic dermatitis, a chronic disease seen by allergist-immunologists, has both dermatologic and ocular manifestations. The ocular component is often disproportionately higher than the dermatologic disease. Even if skin abnormalities seem well controlled, these patients require ophthalmic evaluation. Atopic keratoconjunctivitis in atopic dermatitis patients is characterized by acute exacerbations and requires maintenance therapy for long-term control. Future studies will continue to emphasize the use of steroid-sparing, immunomodulating agents that have the potential to provide long-lasting anti-inflammatory control with a more favorable side-effect profile.

Topics: Adrenal Cortex Hormones; Animals; Blepharitis; Cyclosporine; Dermatitis, Atopic; Humans; Immunomodulation; Keratoconjunctivitis; Risk Factors; Tacrolimus

Topical calcineurin inhibitors (cyclosporin A 1%, FK506, pimecrolimus) can be useful for treating chronic blepharokeratoconjunctivitis in addition to lid hygiene and lubricants. This treatment leads to an improvement of dry eye symptoms and reduces inflammation.

Topics: Administration, Topical; Blepharitis; Calcineurin Inhibitors; Cyclosporine; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Tacrolimus

This prospective, randomized, double-blind interventional case series was designed to evaluate the short-term efficacy of 0.03% tacrolimus ointment as a new therapeutic approach for refractory cases of posterior blepharitis.. Forty eyes (20 patients) with posterior blepharitis refractory to previous treatment were randomized. Eighteen eyes (9 patients) were treated with 0.03% tacrolimus ointment and 20 eyes (10 patients) with placebo ointment twice daily. Patients were evaluated with a questionnaire and slit-lamp examination 14 days and 28 days after treatment, and symptoms and signs of blepharitis were compared to those observed at baseline.. We could observe statistical difference in the outcome measurements of meibomian gland secretion, conjunctival hyperemia, telangiectasia of inferior lid, Rose Bengal, and fluorescein scoring for the study group. As for the symptoms score, we observed statistical difference in the symptoms scoring for pruritus and dry eye sensation in the tacrolimus group.. This study suggests that topical administration of 0.03% tacrolimus ointment can improve some symptoms and some ocular surface status in patients with refractory posterior blepharitis.

Topics: Administration, Topical; Adult; Blepharitis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Meibomian Glands; Middle Aged; Ointments; Prospective Studies; Slit Lamp Microscopy; Tacrolimus; Treatment Outcome

The main objective of this explorative study was to evaluate if tacrolimus ointment could be safer than corticosteroid ointment, with special reference to the intraocular pressure in the treatment of eyelid eczema in patients with atopic keratoconjunctivitis (AKC). Secondary aims were to compare the effects of the treatments on eyelid eczema and their potential impact on ocular surface inflammation.. Tacrolimus 0.1% ointment and clobetasone butyrate 0.05% ointment were compared in a double-masked explorative crossover study. In total, 25 AKC patients were included. Each ointment was applied twice daily for 3 weeks, with 2 weeks of washout before, between, and after treatments. Efficacy was determined by eye examination and the patients' own symptom scoring. Cytology and cytokine measurements were performed on tear samples. Safety parameters were intraocular pressure, presence of bacteria and fungi, and the patients' reports of adverse events. The validity of the crossover design was explored with analysis of variance, and the effect of each medication was calculated with paired t-test and Wilcoxon paired test.. A total of 20 patients completed the study. Both treatments were effective in reducing signs and symptoms of eyelid eczema, with a near superior benefit for tacrolimus in terms of eczema (total skin score) signs (P=0.05). No serious adverse events occurred and interestingly, intraocular pressure was not evidently affected by either treatment.. Tacrolimus 0.1% ointment is a promising alternative therapy for eyelid eczema in AKC patients. Long-term studies are needed to further determine the value of tacrolimus in this patient group.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Biomarkers; Blepharitis; Clobetasol; Cross-Over Studies; Cytokines; Dermatitis, Atopic; Eyelids; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Inflammation Mediators; Intraocular Pressure; Keratoconjunctivitis; Male; Middle Aged; Ointments; Tacrolimus; Tears; Treatment Outcome

Severe atopic blepharitis is difficult to treat, as topical steroids offer only a limited therapeutic benefit with increasing side effects by time. Topical FK 506 was found to be efficient and safe for treatment of atopic dermatitis in dermatologic studies. The use of topical FK 506 in atopic blepharitis has not been reported so far.. Fourteen patients with severe atopic blepharitis were treated with topical FK 506 0.1 %. The ointment was applied twice daily on the eye lids. Ophthalmologic examinations were scheduled at two weeks, two months and five months after onset of treatment. A score was defined for the skin of the lid (edema, erythema, lichenification, oozing, excoriation and crusting) and for the eye lid margin (erythema, thickening, crusting) respectively. Every patient graded pruritus on a visual analogue scale.. The mean skin score prior to treatment was 25.6 +/- 5.8, after two weeks 7.9 +/- 4.8 (p < 0.001), after two months 5.8 +/- 5.0 (p < 0.001) and after five months 5.3 +/- 5.3 (p < 0.001). The mean score for the eye lid margin prior to treatment was 12.3 +/- 4.0, after two weeks 4.6 +/- 2.7 (p < 0.001), after two months 3.8 +/- 2.4 (p < 0.001) and after five months 4.3 +/- 2.6 (p < 0.001). The mean score for pruritus prior to treatment was 8.1 +/- 1.3, after two weeks 2.0 +/- 1.4 (p < 0.001), after two months 1.3 +/- 0.8 (p < 0.001) and after five months 0.8 +/- 0.7 (p < 0.001). All patients assessed the overall situation under therapy as markedly improved.. Topical FK 506 0.1 % ointment turns out to be an excellent therapeutic option for treatment of severe atopic blepharitis. Long-term efficacy and safety have to be evaluated in long-term follow-up studies.

Topics: Administration, Topical; Adult; Blepharitis; Cross-Over Studies; Dermatitis, Atopic; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Patient Satisfaction; Severity of Illness Index; Tacrolimus; Treatment Outcome

Topics: Blepharitis; Dermatitis, Atopic; Eczema; Eyelids; Humans; Immunosuppressive Agents; Tacrolimus; Treatment Outcome

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and has aesthetic, physical, and emotional-social sequelae when left untreated.. To classify the most common adverse reactions associated with dupilumab treatment in patients with AD.. The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions associated with dupilumab, topical pimecrolimus, and topical tacrolimus. Phase III clinical trial data were used to compare the rate of herpes infections between the treatment group and placebo group.. The most common adverse reaction associated with dupilumab was ocular complications. Herpes infections were extremely rare in the patients with AD being treated with dupilumab.. Prescribing information for dupilumab, topical pimecrolimus, and topical tacrolimus is not available. Adverse effects are reported by patients, health care providers, and pharmaceutical companies, they have not been corroborated.. Ocular complications are the most common complication associated with dupilumab. The rate of herpes infection is low in patients being treated with dupilumab, topical pimecrolimus, and topical tacrolimus. There is no significant difference for the rate of herpes infection between, placebo, dupilumab, topical pimecrolimus, and the topical tacrolimus treatment group, suggesting that dupilumab does not affect herpes infection rates.

Topics: Antibodies, Monoclonal, Humanized; Blepharitis; Clinical Trials as Topic; Conjunctivitis; Dermatitis, Atopic; Dry Eye Syndromes; Eye Diseases; Herpesviridae Infections; Humans; Hyperemia; Interleukin-13; Interleukin-4; Retrospective Studies; Tacrolimus; United States; United States Food and Drug Administration; Virus Activation

Allergies are frequently implicated in ophthalmologic practice. These typically benign allergies can be potentially severe for the ocular surface and have an impact in everyday life. We relate, through a case of keratoconjunctivitis involving 2 types of hypersensitivity, the various triggers and therapeutic choices to allow a more effective treatment.

Topics: Adult; Allergens; Animals; Azithromycin; Blepharitis; Cats; Dermatitis, Atopic; Desensitization, Immunologic; Dogs; Drug Therapy, Combination; Eosinophilia; Histamine Antagonists; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Intradermal Tests; Keratoconjunctivitis; Lubricant Eye Drops; Male; Pyroglyphidae; Rhinitis, Allergic, Seasonal; Tacrolimus

Topics: Administration, Topical; Adult; Blepharitis; Cohort Studies; Conjunctivitis, Allergic; Databases, Factual; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Finland; Follow-Up Studies; Humans; Male; Middle Aged; Patient Safety; Retrospective Studies; Severity of Illness Index; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

To report a case of refractory atopic blepharoconjunctivitis (ABC) treated by using topical tacrolimus 0.03% dermatologic ointment.. A 73-year-old man with ABC was refractory to topical corticosteroid treatment.. Topical tacrolimus 0.03% dermatologic ointment (Protopic; Astellas Pharma) was applied into the conjunctival fornix twice each day. Dramatic improvement of patient's symptoms was observed during the first week of therapy. Tacrolimus ointment treatment continued for 12 months. No drug-induced conjunctival hyperemia, ocular surface staining, or other adverse changes were noted secondary to the use of the topical tacrolimus ointment.. Topical tacrolimus 0.03% dermatologic ointment appears to be an effective treatment for ABC that is refractory to conventional therapy.

Topics: Administration, Ophthalmic; Aged; Blepharitis; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Male; Ointments; Tacrolimus; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Blepharitis; Calcineurin Inhibitors; Conjunctivitis, Allergic; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Intraocular Pressure; Male; Middle Aged; Ointments; Retrospective Studies; Tacrolimus; Treatment Outcome; Young Adult

Topics: Administration, Topical; Blepharitis; Chloroquine; Dermatomyositis; Female; Humans; Immunosuppressive Agents; Injections, Intravenous; Middle Aged; Paraneoplastic Syndromes; Tacrolimus; Treatment Outcome

To study corneal abnormalities in the NC/Nga mouse, which is an animal model of atopic dermatitis.. To study histopathologic changes of the eyelid, conjunctiva, and cornea, we extracted the eyeballs together with upper and lower eyelids and fixed them for examination by light and electron microscopy or snap-froze them for immunohistochemistry. Transferase mediated-dUTP digoxigenin nick-end labeling staining was performed to detect apoptotic cells. In order to assess eye scratching behavior and the effect of tacroliums hydrate ointment, we made video recordings.. Mice kept in a conventional room suffered from various grades of blepharoconjunctivitis and scratched their eyes furiously. Tacrolimus hydrate ointment reduced their eye-scratching behavior. Histopathologic study of the eyelid and conjunctiva showed that this blepharoconjunctivitis was caused by allergic inflammation. Mice with severe blepharoconjunctivitis showed thinning of the corneal epithelium, an irregular interface between the epithelium and stroma, subepithelial deposition of materials, and neovascularization of the stroma. Their corneas were cone shaped. Many transferase mediated-dUTP digoxigenin nick-end labeling-positive cells were recognized among superficial epithelial cells and keratocytes.. NC/Nga mice are a useful animal model of atopic blepharoconjunctivitis. Various corneal disorders in these mice may depend on their eye-scratching behavior.

Topics: Animals; Apoptosis; Blepharitis; CD4 Antigens; CD4-Positive T-Lymphocytes; Conjunctivitis, Allergic; Dermatitis, Atopic; Disease Models, Animal; Epithelium, Corneal; Immunoenzyme Techniques; Immunoglobulin E; Immunosuppressive Agents; In Situ Nick-End Labeling; Keratoconus; Male; Mice; Mice, Inbred Strains; Ointments; Specific Pathogen-Free Organisms; Tacrolimus

Topics: Blepharitis; Chronic Disease; Conjunctivitis; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Tacrolimus; Treatment Outcome

To evaluate the efficacy and effect of tacrolimus ointment on conjunctival cytology in patients with atopic blepharoconjunctivitis or keratoconjunctivitis.. 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.. 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.. 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.

Topics: Adult; Blepharitis; Conjunctiva; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Male; Ointments; Retrospective Studies; Tacrolimus; Treatment Outcome

To report 4 cases of patients treated with topical tacrolimus ointment 0.03% for ocular inflammatory conditions refractory to traditional treatment.. Four patients were treated topically with tacrolimus 0.03% ointment twice daily: 2 patients with blepharokeratoconjunctivitis, 1 patient with severe atopic keratoconjunctivitis, and 1 patient with chronic follicular conjunctivitis.. Three patients had a dramatic improvement of their ocular condition as early as 2 weeks after starting tacrolimus ointment. One patient developed a herpes simplex virus dendrite after 1 week of tacrolimus use.. Tacrolimus ointment appears to be an effective alternative for certain ocular inflammatory conditions refractory to traditional treatments. There may be an increased risk of herpes simplex virus keratitis associated with topical use. Our results support previous literature of patients benefiting from topical tacrolimus use.

Topics: Administration, Topical; Adult; Aged; Blepharitis; Chronic Disease; Conjunctivitis; Conjunctivitis, Allergic; Drug Administration Schedule; Female; Humans; Immunosuppressive Agents; Keratitis, Dendritic; Keratoconjunctivitis; Male; Middle Aged; Ointments; Tacrolimus; Treatment Outcome

To report the association of Kaposi varicelliform eruption (KVE) with 0.1% tacrolimus ointment treatment of atopic blepharitis in a patient with atopic dermatitis (AD).. We encountered KVE in a 20-year-old male patient with atopic blepharitis and AD who developed generalized herpetic lesions on his face 28 days after commencement of treatment.. The lesions resolved quickly with intravenous acyclovir treatment.. Ophthalmologists should be well aware of KVE as a complication of immunosuppressive treatment in patients with atopic blepharitis.

Topics: Acyclovir; Adult; Antiviral Agents; Blepharitis; Humans; Immunosuppressive Agents; Kaposi Varicelliform Eruption; Male; Ointments; Tacrolimus; Virus Activation

Experimental immune-mediated blepharoconjunctivitis (EC) in Brown Norway (BN) rats, which is inducible by transfer of antigen-specific T cells, is a model for human allergic conjunctivitis. We investigated the possible inhibition of EC in BN rats by topical application of FK506, which is an immunosuppressive agent that mainly targets T cells.. To induce EC by active immunization, ovalbumin (OVA) adsorbed to alum was injected into the hind footpads of BN rats. Three weeks after the initial immunization, rats were challenged with OVA by eye drops. Twenty-four hours later, lids including conjunctivas, lymph nodes (LNs), and sera were harvested for histology or reverse transcriptase PCR, proliferation assays, and measurement of IgE titer, respectively. For passive immunization, rats were intravenously injected with 10 million of in vitro-stimulated OVA-primed LN cells. Four days after the transfer, rats were challenged with OVA and evaluated as above. The rats were divided into two groups. One group received topical FK506 treatment three times per day from 15 to 21 days after active immunization or from 1 to 4 days after transfer. The other group was treated with vehicle as above.. FK506 treatment suppressed infiltration of both lymphocytes and eosinophils in the conjunctiva either by active or passive immunization (P<0.002). No differences were noted in antigen-specific cellular and humoral immune responses. Concerning cytokine expression in the conjunctiva, a prominent difference was noted only with IL-4, which was more abundantly detected in the vehicle-treated group.. Topical FK506 treatment suppressed EC in BN rats, possibly by inhibition of IL-4 in the conjunctiva.

Topics: Administration, Topical; Animals; Blepharitis; Conjunctivitis; Immunization, Passive; Immunosuppressive Agents; Male; Ophthalmic Solutions; Ovalbumin; Rats; Rats, Inbred BN; Tacrolimus

FK506 has been used for treatment of cell-mediated immune disorders such as graft rejection in transplantation or Behçet disease. To evaluate the effectiveness of FK506 in another ocular disease model, we injected FK506 in rats with experimental allergic/immune-mediated blepharo conjunctivitis (EAC) the induction mechanism of which depends on cell-mediated immunity.. Lewis rats were immunized with ovalbumin (OVA) in emulsion of complete Freund's adjuvant (CFA). We injected 2 (n = 6), 20 (n = 6) or 200 (n = 5) microg of FK506 intramuscularly daily from the day of immunization (day 0) to day 6. Control rats were not treated with FK506 (n = 4). In addition, we injected 200 microg of FK506 from day 7 to day 13 (n = 12) to compare the timing of FK506 administration (day 0 to day 6, n = 12; control, n = 12). Twenty-one days after immunization, all rats were challenged with OVA by eye drops, and 24 h later they were killed after clinical evaluation and their eyes, blood and draining lymph nodes were harvested for histology, antibody titers and proliferation assay or flow cytometric analysis. In another set of experiments, rats that had received OVA-primed lymph node cells did (n = 9) or did not (n = 9) receive additional FK506 by injection daily for 4 days. Four days after transfer, these rats were challenged with OVA and evaluated as mentioned. To investigate possible suppression of disease by topical administration of FK506, both actively immunized and passively immunized rats received OVA together with 0.3% (weight/volume) of FK506 (n = 16) or vehicle (n = 10) by eye drops and 24 h after challenge, rats were evaluated as mentioned.. Development of disease, induced by either active or passive immunization, was inhibited in the group treated with 200 microg of FK506, regardless of timing of administration. Cellular proliferative responses to OVA were inhibited only in this group. Flow cytometry demonstrated a decrease of about 20% in the proportion of all cells made up by CD4-positive T cells. Topical administration of FK506 inhibited the development of EAC, though not significantly.. Systemic treatment with 200 microg of FK506 either in the induction or the effector phase inhibits the development of EAC in Lewis rats. Topical administration is not so effective as systemic administration.

Topics: Adoptive Transfer; Animals; B-Lymphocytes; Blepharitis; CD3 Complex; CD4-Positive T-Lymphocytes; Conjunctivitis, Allergic; Disease Models, Animal; Immunosuppressive Agents; Injections, Intramuscular; Leukocyte Common Antigens; Lymph Nodes; Lymphocyte Activation; Male; Ophthalmic Solutions; Ovalbumin; Rats; Rats, Inbred Lew; Tacrolimus; Vaccination