tacrolimus and Conjunctivitis--Allergic

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments.

Topics: Conjunctivitis, Allergic; Cyclosporine; Humans; Ophthalmic Solutions; Tacrolimus; Ulcer

Tacrolimus has been widely used in recent years for treating allergic conjunctivitis, but there is currently no available meta-analysis regarding its therapeutic efficacy. This study systematically evaluated the effectiveness of tacrolimus in the treatment of allergic conjunctivitis.. Data obtained from literature searches of the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases were retrieved by combining medical subject words and free words. Literature was selected on the basis of established inclusion and exclusion criteria, and the extracted data were evaluated for risk of bias using RevMan 5.3 for meta-analysis.. A total of 177 articles were retrieved, of which 5 articles were eventually selected, all of which involved tacrolimus treatment for vernal keratoconjunctivitis. A total of 203 samples were analysed. Results of the meta-analysis showed that the tacrolimus treatment group had significantly lower ocular objective sign scores (SMD -1.39, 95% CI -2.50 to -0.27; p<0.05) and had a significantly lower subjective symptom evaluation score (SMD -0.92, 95% CI -1.59 to -0.24; p<0.05) than the control group.. Current evidence shows that tacrolimus is effective in treating vernal keratoconjunctivitis.

Topics: Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Tacrolimus

The purpose of this article is to provide an update on the advances made through recent clinical trials regarding the treatment of the signs and symptoms of allergic conjunctivitis and its associated conditions.. Recent studies have demonstrated significant advancement in the various forms of immunotherapy treatments. Nutritional interventions such as probiotics have surfaced as a viable complementary treatment option. Novel delivery methods such as contact lenses have been further studied along with a new tacrolimus formulation to improve ocular levels of the drug.. Currently, the primary advances in treatment for allergic conjunctivitis has shifted from new ophthalmic agents to immunotherapy and improvement of drug delivery. This includes the classic subcutaneous and sublingual and the novel epicutaneous and intralymphatic immunotherapy delivery systems as well as an edible rice vaccine. New targets for treatment have spurred research into new antagonist drugs such as (OC000459), a prostaglandin D2 antagonist. The Marinosolv formulation using tacrolimus shows promise and may be considered for other ophthalmic agents in the future. Other nonpharmacological treatments such as stenting and mechanical barrier gel have demonstrated their usefulness in treating ocular symptoms.

Topics: Administration, Sublingual; Clinical Trials as Topic; Conjunctivitis, Allergic; Desensitization, Immunologic; Humans; Indoleacetic Acids; Quinolines; Tacrolimus; Vaccines

The spectrum of allergic eye diseases includes a variety of conditions, each characterized by complex immunopathologies.Antiallergic drugs, such as antihistamines and mast cell stabilizers, are often insufficient without concomitant topical corticosteroid treatment. The chronic course of the more severe allergic eye diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), limits the treatment with topical corticosteroids to short courses. In addition, topical corticosteroid treatment puts patients at high risk of developing severe ocular complications, particularly during childhood when VKC most frequently occurs.The immunopathology of chronic diseases, such as VKC and AKC, involves predominantly T lymphocytes, and as such, immunomodulators that inhibit T-cell activation seem to be the appropriate treatment for these chronic diseases. In the past years, there is an increased incidence of managing chronic allergic eye diseases with the immunomodulator tacrolimus. The current review presents an update of the recent clinical experience with topical tacrolimus for the management of chronic allergic eye diseases.. Topical tacrolimus significantly improves the symptoms and signs of the various forms of chronic allergic eye disease. Recent studies also demonstrate the efficacy of low concentrations of topical tacrolimus for VKC.Early medical treatment with topical tacrolimus can also prevent the development of serious ocular complications of VKC, such as shield ulcers or limbal stem cell deficiency.. Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids.

Topics: Administration, Topical; Adrenal Cortex Hormones; Chronic Disease; Conjunctivitis, Allergic; Humans; Immunologic Factors; T-Lymphocytes; Tacrolimus

Contact lens-induced papillary conjunctivitis (CLPC) is a common ocular allergic disease in contact lens wearers. In its more severe form, it can cause giant papillary conjunctivitis, resulting in contact lens intolerance and the need to discontinue the use of contact lenses. This review presents the pathogenesis, clinical manifestations and management guidelines of this common disorder.. Different types of contact lenses are associated with differences in the severity of CLPC. Refitting patients with silicone hydrogel contact lenses or with daily disposable contact lenses may improve the signs and symptoms of CLPC. The recent introduction of the topical immunomodulatory agent tacrolimus in other severe allergic eye diseases may apply in suppressing the allergic inflammation in CLPC as well.. CLPC is a common ocular disorder in contact lens wearers, with a significant impact on the quality of vision. It should be promptly recognized by healthcare practitioners and managed by modifications of the types and wearing schedules of contact lenses, as well as novel treatment options with topical immunomodulators.

Topics: Animals; Conjunctivitis, Allergic; Contact Lenses; Eye; Humans; Hypersensitivity; Immunomodulation; Tacrolimus

Topical calcineurin (Cn) inhibitors delivered via ophthalmic drop is emerging as a potential treatment for severe, immune-mediated forms of allergic conjunctivitis, such as vernal keratoconjunctivitis, atopic keratoconjunctivitis and giant papillary conjunctivitis.. This article is based on a comprehensive literature search, with information taken from meta-analyses, systematic reviews, treatment guidelines and clinical studies in children and adults. The articles that have been selected evaluate the use of topical Cn inhibitors and their role in the treatment of allergic conjunctivitis.. Ophthalmic topical Cn inhibitors have been shown to be safe for short-term use, with minimal systemic absorption and toxicity. For patients with severe, refractory forms of allergic conjunctivitis, topical Cn inhibitors offer a promising treatment option and an alternative to steroidal therapies. The safety profile and efficacy data for topical cyclosporine are more robust compared to that of tacrolimus and pimecrolimus, although larger trials will be needed for all three agents. With more randomized controlled trials involving larger sample sizes and long-term follow-up to establish both efficacy and safety, ophthalmic Cn inhibitors offer exciting treatment possibilities for the prevention of morbidity associated with refractory allergic conjunctivitis.

Topics: Administration, Ophthalmic; Calcineurin Inhibitors; Conjunctivitis, Allergic; Cyclosporine; Humans; Immunosuppressive Agents; Tacrolimus; Treatment Outcome

Allergic eye diseases comprise a spectrum of diseases, with each condition being characterized by a complex immunopathology. The more severe and chronic conditions, such as vernal keratoconjunctivitis and atopic keratoconjunctivitis, involve predominantly mast cells and eosinophils, while also being associated with a preponderance of T cells. Treatment with topical antihistamines or mast cell stabilizers is often unsatisfactory, and therapy depends on topical corticosteroids. Corticosteroids have significant side-effects with long-term use; therefore, they appear to be more appropriate for short-term pulse therapy. Immunomodulatory agents can also be used to inhibit T-cell activation and show encouraging results among patients with severe allergic eye conditions. The present review is an attempt to present a coherent picture of the recent investigations of topical immunomodulatory agents' therapy in severe allergic eye diseases, especially cyclosporine A and tacrolimus, and their mechanisms of action.. Immunomodulatory agents are commonly indicated for the treatment of severe and prolonged allergic conjunctivitis. This article reviews the recent studies of these drugs and the development of immunomodulatory treatments for severe allergic eye diseases.. Cyclosporine A and tacrolimus are currently available for the treatment of severe allergic conjunctivitis. These agents have led to improved therapeutic results for patients with severe and chronic allergic eye diseases.

Topics: Administration, Topical; Adrenal Cortex Hormones; Conjunctivitis, Allergic; Cyclosporine; Eosinophils; Eye; Humans; Immunomodulation; Lymphocyte Activation; Mast Cells; T-Lymphocytes; Tacrolimus; Treatment Outcome

Vernal keratoconjunctivitis is a sight-threatening inflammatory disease of conjunctiva and cornea. It is frequently observed in young children with the onset usually occurring in the first decade of life. Mild cases of VKC tend to remit with nonspecific and supportive therapy. In contrast, severe cases are usually more protracted with remission/relapse occurring for a prolonged period of time. Although VKC is classified as an allergic eye condition, the role of allergens as an inciting factor is not clear. Pathogenesis of VKC involves roles for IgE, cytokines, chemokines, and inflammatory cells (T and B lymphocytes, mast cells, basophils, neutrophils, and eosinophils) with the release of their granular proteins, proliferation of fibroblasts, and laying down exuberant amounts of collagen fibers in the conjunctival tissue. In severe VKC cases-often of tarsal VKC-diagnostic giant papilla are classically observed on the upper tarsal plate, giving the classic 'cobble-stone' appearance. Corneal ulcer can occur from the effect of eosinophilic granular proteins on corneal epithelium and by physical trauma by intense eye rubbing. Topical corticosteroids, often required for controlling symptoms and signs in severe VKC, can lead to serious ocular complications. Immunomodulators that have been investigated for VKC treatment include topical ocular preparations of cyclosporine A and tacrolimus. Severe VKC responds promptly to topical cyclosporine A and tacrolimus, mostly within 1 month of therapy. Prolonged use of cyclosporine A and tacrolimus in VKC is safe and is tolerated by most patients without significant side effects. Recent investigations on the use of these two agents in VKC are the main purpose of this review. The use of cyclosporine A and tacrolimus are a major breakthrough in treatment for severe VKC, a debilitating allergic eye disease in children.

Topics: Allergens; Conjunctiva; Conjunctivitis, Allergic; Cyclosporine; Cytokines; Epithelium, Corneal; Humans; Immunosuppressive Agents; Ophthalmic Solutions; Recurrence; Tacrolimus

Seasonal atopic conjunctivitis is treated with antihistamines, cromoglycate and short courses of corticosteroids, in severe cases with subcutaneous or sublingual immunotherapy. Chronic conjunctivitis requires year-round treatment with mast cell stabilizers, antihistamines or topical corticosteroids. Long-term treatment of atopic blepharoconjunctivitis consists of tacrolimus or pimecrolimus cream. For atopic keratoconjunctivitis corticosteroid and, if necessary, cyclosporine eye drops are needed. First-line therapy of vernal conjunctivitis involves mast cell stabilizers and, if necessary, corticosteroid eye drops. Treatment of non-allergic eosinophilic conjunctivitis involves mast cell stabilizers, corticosteroid and, if necessary, cyclosporine eye drops.

Topics: Adrenal Cortex Hormones; Conjunctivitis, Allergic; Cromolyn Sodium; Cyclosporine; Histamine Antagonists; Humans; Immunosuppressive Agents; Tacrolimus

To report the utility of tacrolimus 0.03% dermatologic ointment (Protopic) in a case of refractory atopic keratoconjunctivitis with giant papillae. A review of the medical literature is presented.. A 32-year-old man with a long-standing history of severe atopic disease was referred to our department because of bilateral intense eye pain, itching, photophobia, and epiphora. Biomicroscopy examination showed conjunctival hyperemia, superficial punctata keratitis, and tarsal giant papillae. This patient had undergone previous treatment with systemic and topical steroids, antihistamines, topical antihistamine/mast cell stabilizer drops, cyclosporine A, and even surgical resection-cryopexy of giant papillae-without success.. The patient was started on tacrolimus 0.03% ointment treatment of the conjunctival fornix twice daily. After 2 months, the patient experienced resolution of his clinical symptoms with a significant decrease in papillae size. No side effects were reported. Treatment was continued for 1 month and gradually reduced with increasingly wide intervals between applications. Eight months after treatment, there were no signs of reactivation, and the patient remains asymptomatic.. Application of tacrolimus 0.03% dermatologic ointment into the lower fornix seems to constitute an interesting alternative treatment for atopic keratoconjunctivitis that is refractory to traditional treatment.

Topics: Administration, Topical; Adult; Chronic Disease; Conjunctiva; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Male; Ointments; Tacrolimus; Treatment Outcome

This review will focus on the diagnostic features of atopic keratoconjunctivitis (AKC), its relationship to atopic dermatitis, the immunopathogenesis, and therapy, and will include strategies used for the management of severe disease unresponsive to conventional therapy.. Recent research has demonstrated the importance of various cytokines (IL-33), proteins (thymic stromal lymphopoetin) and effector cells (conjunctival epithelial cells, eosinophils and basophils) in the pathogenesis of chronic ocular inflammation. Current evidence supports the use of tacrolimus and cyclosporin A, topically or systemically, as well tolerated and effective steroid sparing agents.. Recalcitrant AKC may be a blinding condition. Understanding the immunopathogenesis of atopic dermatitis and AKC has already influenced therapy and is essential to the development of future immunomodulatory treatments. The successful management of AKC requires the use of topical cromones, antihistamines and calcineurin inhibitors. Severely affected patients also require systemic immunosuppressive therapy. The current challenge is to find more specific topical and systemic immunomodulatory therapies with a better side-effect profile.

Topics: Basophils; Conjunctivitis, Allergic; Cyclosporine; Cytokines; Dermatitis, Atopic; Drug Resistance; Eosinophils; Epithelial Cells; Humans; Interleukin-33; Interleukins; Keratoconjunctivitis; Tacrolimus; Thymic Stromal Lymphopoietin

The paper presents some notes about the type of cellularity involved in principal ocular allergy determinate by an allergic mechanism and tries a correspondence with a logical and target treatment, with maximum efficiency.

Topics: Adrenal Cortex Hormones; Conjunctivitis, Allergic; Cyclosporine; Drug Therapy, Combination; Eosinophils; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Mast Cells; Ophthalmic Solutions; Tacrolimus; Treatment Outcome

Allergic eye disease is a term that refers to a number of disease processes that affect about one-fifth of the world's population. Although the more advanced forms of the disease can be sight threatening, the most disabling effects are due to the clinical manifestations, and hence quality of life, with some patients having seasonal exacerbations of their symptoms, whereas others have symptoms that are present throughout the year. Recent increased understanding of the cellular and mediator mechanisms that are involved in the various disease manifestations has greatly facilitated the development of more effective treatment options. Newer topical medications are being used that have multiple actions, such as an antihistaminic effect coupled with mast-cell stabilisation, and which require reduced daily dosing due to their longer duration of action. With greater research into newer therapies and more effective modes of delivery, improved healthcare outcomes with a lower economic burden will be achieved for patients with allergic eye disease.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Conjunctivitis, Allergic; Cost of Illness; Dibenzoxepins; Drug Administration Schedule; Health Care Costs; Histamine H1 Antagonists; Humans; Immunosuppressive Agents; Mast Cells; Olopatadine Hydrochloride; Phthalazines; Quality of Life; Randomized Controlled Trials as Topic; Tacrolimus; Vision Disorders

Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, external ocular inflammatory disorder that mainly affects patients in their first or second decade. This study was designed to compare tacrolimus and interferon alpha-2b (IFN alpha-2b) eye drops in the treatment of VKC.. In this randomized, double-masked clinical trial, 40 consecutive patients with VKC were sent to a referral eye hospital in a tropical region southeast of Iran. Patients were randomly assigned to receive either 0.005% tacrolimus or IFN alpha-2b (1,000,000 units/cc). Chi-square and t tests were used for comparison of outcomes between both groups.. Mean ± SD age was 11.1 ± 5.2 years. Thirty-one patients (77.5%) were male. The mean duration of disease was 3.4 ± 2.9 years. In this study, the signs and symptoms were significantly reduced in patients after treatment in both groups (P = 0.0001). In the tacrolimus group, all patients responded to treatment whereas only one subject in the IFN group failed to respond (P = 0.99). Side effects in both groups were mild and tolerable.. This study indicated that both 0.005% tacrolimus and IFN alpha-2b are effective and appear to be safe in treatment of recalcitrant VKC.

Topics: Adolescent; Child; Conjunctivitis, Allergic; Double-Blind Method; Female; Humans; Immunologic Factors; Immunosuppressive Agents; Interferon alpha-2; Interferon-alpha; Male; Ophthalmic Solutions; Recombinant Proteins; Tacrolimus

To assess the efficacy of monotherapy using tacrolimus eye drops versus sodium cromoglycate for the treatment of vernal keratoconjunctivitis (VKC).. Randomized double-masked controlled trial comparing the efficacy of tacrolimus 0.03% eye drops t.i.d. (Group 1) with sodium cromoglycate 4% eye drops t.i.d. (Group 2) for the symptomatic control of VKC at days 0, 15, 30, 45, and 90 of follow-up. Visual acuity, intraocular pressure, and other complications were evaluated to assess safety and side effects.. In total, 16 patients were included, with 8 enrolled in each group. Two patients from Group 2 were excluded from the analysis at days 45 and 90 because of corticosteroid use. Most patients were male (81.8%) and presented with limbal VKC (56.3%). There were statistically significant differences in favor of tacrolimus in the following severity scores: itching at day 90 (p=0.001); foreign body sensation at day 15 (p=0.042); photophobia at day 30 (p=0.041); keratitis at day 30 (p=0.048); and limbal activity at days 15 (p=0.011), 30 (p=0.007), and 45 (p=0.015). No relevant adverse effects were reported, except for a burning sensation with tacrolimus, though this did not compromise treatment compliance.. Treatment with tacrolimus was superior to sodium cromoglycate when comparing severity scores for symptoms of itching, foreign body sensation, and photophobia, as well as for signs of limbal inflammatory activity and keratitis.

Topics: Adolescent; Child; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Severity of Illness Index; Statistics, Nonparametric; Tacrolimus; Time Factors; Treatment Outcome; Visual Acuity

The aim of the study was to evaluate and compare the efficacy, side effects and recurrence rate of vernal kerato conjunctivitis (VKC) with 0.03% tacrolimus and 0.05% cyclosporin.. A prospective randomised double blinded comparative study was conducted at a tertiary eye center. 46 Patients of VKC between March 2015- August 2015 were randomly divided into two groups and treated for 6weeks with either Tacrolimus(0.03%) eye ointment BD or Cyclosporine (0.05%) eyedrops QID.The main outcome measures were scoring and comparison of Total subjective symptom scores (TSSS) and Total objective ocular sign scores (TOSS) within and between the Groups at each follow up.Thirty two patients, sixteen from each group, with comparable baseline characters were analysed.. With treatment both TSSS and TOSS decreased consistently in both groups without any adverse effects but an increase in scores was noticed within two weeks after drug withdrawal.. Both drugs are equally effective and safe in VKC but with short lasting effect.

Topics: Child; Child, Preschool; Conjunctiva; Conjunctivitis, Allergic; Cornea; Cyclosporine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Ointments; Ophthalmic Solutions; Prospective Studies; Recurrence; Tacrolimus; Treatment Outcome

Vernal keratoconjunctivitis (VKC) is a chronic sight-threatening ocular disease. Topical cyclosporine A (Cyc) has been widely administered as a steroid-sparing drug, although in about 7-10% of cases, it has been ineffective. The purpose of this study was to evaluate the efficacy of 0.1% topical tacrolimus (Tcr) in patients with severe VKC who failed to respond to 1% Cyc eyedrops.. Consecutive patients with severe, Cyc-resistant VKC were enrolled in a double-blind, comparative, crossover (DBCO) trial; all patients were treated with 1% Cyc in one eye and 0.1% Tcr in the other eye for 3 wk. After a washout period of 7 days, patients were instructed to cross over the medications for three additional weeks. Objective ocular score, subjective score, and quality-of-life questionnaires (QoLQ) were collected during the trial. Blood samples were drawn to assess several safety parameters.. Thirty patients have been enrolled (mean age 9.05 ± 2.12 yr). In each of the two phases of the DBCO trial, a significant improvement in objective and subjective scores was observed in the eyes treated with 0.1% Tcr (p < 0.001). Likewise, the quality of life significantly improved despite only half the eyes being successfully treated. Serum creatinine and blood parameters were constantly within the normal range, and both blood Cyc and Tcr concentrations remained below the lowest detectable levels.. Topical Tcr is very effective and safe in the short term for patients suffering from severe VKC resistant to topical Cyc.

Topics: Child; Conjunctivitis, Allergic; Creatinine; Cross-Over Studies; Cyclosporine; Disease Progression; Double-Blind Method; Drug Resistance; Eye; Female; Humans; Male; Ophthalmic Solutions; Quality of Life; Tacrolimus

This study sought to evaluate the efficacy of the isolated use of tacrolimus compared with the combined use of tacrolimus and olopatadine for the treatment of severe vernal keratoconjunctivitis (VKC).. Twenty-one patients with severe VKC were randomized into two groups: one treated with 0.03% tacrolimus ointment combined with 1% olopatadine ophthalmic solution and the other with 0.03% tacrolimus ointment combined with placebo eye drops. The clinical signs and symptoms were graded from 0 to 3, and the efficacy of treatment was determined by the difference between the score at the beginning of treatment and after 30 days. The clinical impression of improvement as perceived by the evaluator and the self-assessment provided by the patient were scored at day 30 of treatment and compared between the groups.. The scores for symptoms decreased between the assessments in both groups (-1.7±3.9 in the experimental group; -0.6±1.6 in the control group), with no significant difference between groups (P=0.205). The scores for clinical signs decreased between the assessments in the experimental group (-1.1±2.7) and increased in the control group (0.3±0.9) but with no significant differences (P=0.205). There was no significant difference between the groups regarding the self-assessment (P=0.659) and the clinical impression of the evaluator (P=0.387).. The isolated use of tacrolimus and the combined use of tacrolimus and olopatadine seems to have the same efficacy, although controlled studies with larger samples are required to confirm this hypothesis.

Topics: Administration, Topical; Adolescent; Child; Child, Preschool; Conjunctivitis, Allergic; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Prospective Studies; Tacrolimus

To estimate the efficacy and safety of 0.1% tacrolimus ophthalmic suspension based on the blood level of tacrolimus in patients with severe allergic conjunctivitis.. Fifty-two patients in whom topical anti-allergic agents had been ineffective were treated with 0.1% tacrolimus ophthalmic suspension twice daily for 12 weeks. Adverse drug reactions were monitored, as well as ocular symptoms and signs. The blood concentration of tacrolimus was measured before the initiation of treatment and 4 and 12 weeks later.. About 75% of the patients without concomitant using of tacrolimus ointment had blood levels of tacrolimus below the detection limit of the assay (0.5ng/mL). On the other hand, 71% (week 4) and 57% (week 12) of patients with concomitant using of tacrolimus ointment had blood levels above the detection limit of the assay. However, the maximum blood concentration was less than 2ng/mL. Adverse drug reactions occurred in 16 patients. These were disorders of the eye such as warmness, irritation, and a burning sensation. However, all of the patients could continue treatment with tacrolimus for 12 weeks. There were no serious adverse events such as increased intraocular pressure or ocular infection during the study. All symptoms and signs improved over time.. The good safety profile of 0.1% tacrolimus ophthalmic suspension based on the low blood concentration of tacrolimus, coupled with demonstrated efficacy, make it an important tool for treating severe allergic conjunctivitis.

Topics: Adolescent; Adult; Child; Conjunctivitis, Allergic; Disease Progression; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Prospective Studies; Suspensions; Tacrolimus; Treatment Outcome; Young Adult

The purpose of this study was to compare the efficacy of tacrolimus, fluorometholone, and saline in the treatment of mild to moderate contact lens-induced papillary conjunctivitis (CLPC).. This was a double-masked, randomized pilot study. A total of 18 soft contact lens users (n = 36 eyes) with mild to moderate papillary conjunctivitis were enrolled. Subjects were randomly assigned into three groups to receive tacrolimus 0.05%, fluorometholone 0.1%, or saline (sodium chloride 0.9%). Drugs were prescribed at the baseline visit (visit 1) and instilled twice daily for 4 weeks. Follow-up visits were taken at week 1 (visit 2), week 2 (visit 3), week 4 (visit 4, drug usage suspended at this visit), and week 6 (visit 5, 2 weeks after interrupting eye drops). Contact lens use was discontinued during the 6 weeks of the study, and variables assessed were symptoms and signs, tear film status, and intraocular pressures. Conjunctival impression cytology was performed at baseline and visit 5 to assess ocular surface status.. Mean roughness and redness scores decreased significantly from visit 1 to visit 5, but the variation tendency was comparable in all groups (P = 0.180 and 0.889, respectively). Subjective symptom parameters were improved in all CLPC patients at visit 5, and there was no remarkable difference in symptom reduction in three groups. The mean Schirmer value and mean break-up time (BUT) did not change significantly in the three groups during the study. Ocular surface findings by impression cytology improved significantly after three treatments. Intraocular pressure fluctuation from baseline to 6-week follow-up was not statistically significant in all subjects. No adverse treatment-related event was observed in any study group.. Tacrolimus 0.05% may be a safe and effective treatment for mild to moderate CLPC and is comparable with fluorometholone 0.1% in efficacy. Contact lens cessation accompanied with saline may also be effective in treating mild to moderate CLPC.

Topics: Adolescent; Anti-Allergic Agents; Conjunctivitis, Allergic; Contact Lenses, Hydrophilic; Fluorometholone; Humans; Immunosuppressive Agents; Ophthalmic Solutions; Pilot Projects; Sodium Chloride; Tacrolimus; Treatment Outcome; Young Adult

To compare the efficacy of 0.1% tacrolimus (FK-506) ophthalmic ointment with 2% cyclosporine eye drops in the treatment of vernal keratoconjunctivitis (VKC).. Prospective double-masked randomized comparative trial.. Twenty-four VKC patients were enrolled into the study. Their mean age was 9.61 +/- 2.55 years. Twelve patients were allocated into the FK-506 group and the other twelve into the cyclosporine group. Their baseline characteristics were similar between groups.. After a 2 week run-in period, patients were randomized into 2 groups in a double-masked, parallel fashion. Group A received 0.1% FK-506 eye ointment twice daily with placebo eye drops four times daily for 8 weeks. Group B received 2% cyclosporine eye drops with placebo ointment for the same duration. All patients received an open-treatment with 0.1% FK-506 eye ointment for another 4 weeks. Subjective ocular symptoms and side effects were recorded by patients once daily, during the entire period. Objective ocular signs were evaluated and scored at each follow up visit.. Improvement of total subjective symptom scores per day (TSSS) within group and between groups at various time points.. For within group comparison, there was a significant decrease in TSSS, compared to their baselines, at weeks 4 and 8, in both treatment groups. However, no statistical difference in TSSS was noted between groups at any time point. Total ocular sign scores (TOSS) in the FK-506 group decreased significantly at weeks 4 and 8 compared to baseline. Although there was a decrease of TOSS in the cyclosporine group, the difference did not reach statistical significance. Side effect scores reduced significantly in both groups at week 4 compared to their respective baselines (p = 0.034 in the FK506 group and p = 0.003 in the cyclosporine group). There was no significant difference in the comparison between groups on TOSS and side effect scores at any time point of the study. During the open FK-506 period, patients in cyclosporine group showed further reduction of both TSSS and TOSS. However, these changes were not statistically significant (p > 0.05).. 0.1% FK-506 eye ointment and 2% cyclosporine were both effective in treatment of VKC. 0.1% FK-506 could become another viable therapeutic option for VKC.

Topics: Adolescent; Child; Child, Preschool; Conjunctivitis, Allergic; Cyclosporine; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Ointments; Ophthalmic Solutions; Prospective Studies; Tacrolimus

To examine the efficacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis.. This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary efficacy endpoint was change in the total score of objective signs at the end of treatment. The secondary efficacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events.. Mean change from baseline in total score for objective signs was significantly greater in the tacrolimus (-5.6 + or - 5.1) than in the placebo group (-0.1 + or - 4.5; P < 0.001). Tacrolimus significantly improved giant papillae (P = 0.001) and corneal involvement (P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were significantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated.. Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis.

Topics: Adolescent; Conjunctivitis, Allergic; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Incidence; Male; Ophthalmic Solutions; Sickness Impact Profile; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Child; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Male; Ointments; Ophthalmic Solutions; Tacrolimus; Treatment Outcome

Topics: Biomarkers; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Tacrolimus; Treatment Outcome

Management of allergic eye disease is seldom straightforward and often challenging. We conducted an online survey to elicit opinions on the preferred practice pattern in the treatment of allergic eye disease.. An online survey questionnaire was sent to all practicing ophthalmologists using social media platforms. The respondents were asked about their clinical experience and preferred treatment in various scenarios such as mild-moderate vernal keratoconjunctivitis (VKC), chronic VKC, refractory VKC, steroid responders, giant papillae, and shield ulcer. Respondents were asked about the newer molecule (alcaftadine) and reservations regarding systemic immuno-suppressants and ordering allergy tests in their practice.. Ninety - one participants responded to the survey. About 57.1% of ophthalmologists reported coming across more than 10 cases per week in their practice. The most common age group was 5-10 years (61.1%), but adult onset VKC was also reported at 41.6% (1-2 per month), 37.1% (3-5 per month), and 13.5% (more than 10 per month). The disease is perennially present (36.7%), and a mixed form has been reported by 47.8% of ophthalmologists. Dual-acting agents were preferred by 40% in mild-moderate clinical variants. Topical steroids in slow tapering dosage were preferred by 86.7% in their prescription. Tacrolimus 0.03% was preferred by 65.9% and given for at least 3 months of continuous usage by 47.6% of ophthalmologists. High-dose topical steroids were preferred for giant papillae (67.8%) and Shields ulcers (68.3%) in our survey. Supratarsal steroid injection was preferred by 50% in treating refractory VKC in our survey.. Allergic eye disease is a common yet annoying disease. The signs and symptoms can vary from subtle, innocuous forms to devastating variants affecting vision and day-to-day work. This survey aims to elicit responses from clinicians spreading across different geographical areas and compares responses based on experience in practice.

Topics: Adult; Child; Child, Preschool; Conjunctivitis, Allergic; Humans; India; Ophthalmologists; Steroids; Tacrolimus

To evaluate the clinical improvement and safety of prolonged treatment of vernal (VKC) and atopic keratoconjunctivitis (AKC) using topical tacrolimus.. We included 36 eyes of 36 patients who had VKC and AKC and were treated with topical tacrolimus ophthalmic suspension (0.1%) for 24 months. The demographic data of the enrolled patients were collected from their medical files. Clinical scores, remission rates, number of relapses, concomitant use of steroids, and refractory indices were assessed. Clinical outcomes were determined using papillae-limbus-cornea (PLC) scores and 5-5-5 exacerbation grading scale scores. Clinical characteristics associated with the need for concomitant steroid eye drops administration were determined using logistic regression analysis. All patients were classified into 3 subgroups using cluster analysis.. PLC scores recorded in the sixth month were significantly improved compared with those recorded at baseline. PLC scores recorded in the 18th, 21st, and 24th months were significantly improved compared with those recorded in the sixth month. The remission rates increased diachronically and significantly, reaching 92% in the 24th month. Logistic regression analysis showed that, for every 10-year increase in patient age, the risk for requiring concomitant administration of steroid eye drops was reduced by half (odds ratio, 0.53; 95% confidence interval, 0.29-0.96). Using cluster analysis, the patients were divided into 3 clusters: adolescent type, pediatric type, and adult type.. Two years of treatment with topical tacrolimus ophthalmic suspension is an effective method for inducing and maintaining the stable stages of VKC and AKC.

Topics: Conjunctivitis, Allergic; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Male; Ophthalmic Solutions; Recurrence; Seasons; Tacrolimus; Time Factors; Treatment Outcome; Young Adult

We investigated ocular surface microbiota dysbiosis in patients with refractory allergic conjunctival diseases (ACDs; stratified into mild and severe groups) treated with topical tacrolimus.. Patients (n = 21) with refractory ACDs (including vernal and atopic keratoconjunctivitis) actively treated with topical tacrolimus and 6 healthy controls were evaluated. Based on clinical scores and expression of specific cytokines on the ocular surface, patients with ACDs were divided into mild and severe groups using cluster analysis. The microbial composition of tear specimens collected from patients with mild and severe ACD and control subjects using the Schirmer test paper was determined through next-generation 16S rRNA sequencing analysis.. Compared with healthy controls, patients with ACDs exhibited significantly decreased ocular surface microbiota α-diversity. Ocular surface microbiota mainly comprised members of the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria in all groups. The relative abundance of ocular surface microbiota in patients with ACDs was increased for phylum Firmicutes and decreased for phylum Proteobacteria (compared with control subjects). The genera Blautia (vs. mild ACD group) and Morganella (vs. control group) exhibited significantly increased abundance only in the severe ACD group.. The ocular surface microbiota in patients with severe ACD exhibited decreased diversity and exacerbation of dysbiosis compared with that in patients with mild ACD and control subjects. Patients with mild refractory ACD also exhibited decreased diversity of these microbiota. These alterations in microbiota indicated a change in the ocular surface of patients with refractory ACD (be it because of disease pathogenesis or topical immunomodulatory treatment).

Topics: Conjunctiva; Conjunctivitis, Allergic; Cytokines; Dysbiosis; Humans; Microbiota; RNA, Ribosomal, 16S; Tacrolimus

The aim of this study was to compare treatment regimens of tacrolimus and of topical steroids for VKC and suggest a treatment protocol according to our clinical experience.. This retrospective, nonrandomized case series enrolled 85 patients with VKC. Patients were classified clinically according to severity (mild, moderate, severe) and were treated according to a suggested protocol. Analysis was made according to treatment received: tacrolimus ointment as first line treatment (tacrolimus 1st line), tacrolimus ointment after topical steroid drops treatment (tacrolimus 2nd line) and topical steroid drops or artificial tears alone (topical steroid and tears group).. Significant improvements in clinical signs and symptoms were achieved under tacrolimus treatment 14 months in the moderate group and 5 months in the severe group. The longest duration of treatment was for tacrolimus 2nd line group (p = 0.031) and the mean number of visits in the clinic was the highest. The mean number of topical treatments per day was higher in the topical steroid and tears group (2.6 times) than in the two tacrolimus groups (1.3 times for both). The mean time needed to achieve disease remission or relief did not differ between the tacrolimus 1st line and 2nd line groups.. Tacrolimus treatment is effective and safe for VKC. Tacrolimus as 1st line treatment may be preferred for severe cases, for faster disease remission compared to tacrolimus as 2nd line treatment; and with fewer topical treatments per day compared to topical steroids.

Topics: Administration, Topical; Clinical Protocols; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Ointments; Prospective Studies; Retrospective Studies; Steroids; Tacrolimus; Treatment Outcome

To assess the safety of dermatological 0.1% tacrolimus ointment when used topically and its efficacy in the treatment of vernal keratoconvinctivtis.. The quasi-experimental, multi-centre study was conducted at the Gujranwala Medical College/District Headquarters Teaching Hospital, Gujranwala, and the Gomal Medial College/Mufti Mehmood Teaching Hospital, Dera Ismail Khan, Pakistan, from July 2019 to March 2020, and comprised patients of severe vernal keratoconvinctivtis. Symptoms and clinical signs were graded on a pre-devised scale. Patients were given small amount of tacrolimus 0.1% ointment applied to the inferior conjunctival fornix before going to bed. The duration of treatment was 3 months and the patients were followed up for up to 6 months. Data was analysed using SPSS 20.. Of the 50 patients, 30(60%) were males and 20(40%) were females. The overall mean age was 10.64±3.199 years. Mean symptom score and clinical signs score gradually reduced on each follow-up (p<0.05). Mild recurrence was noted in 12(24%) patients who were managed with lubricants and anti-histamine topical drops. No complication was noted.. Tacrolimus 0.1% was found to be effective and safe in the treatment of severe refractory vernal keratoconvinctivtis even when given once a day.. Chinese Clinical Trial Registry Id: ChiCTR2000031929 link: www.chictr.org.cn/hvshowproject.aspx?id=28053.

Topics: Adolescent; Child; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Lubricants; Male; Ointments; Tacrolimus; Treatment Outcome

Allergic conjunctivitis (AC) is the most common ocular condition in allergic children. In tropical countries, the study about the clinical features and outcome of treatment is very limited.. To review clinical characteristics and outcomes of treatment in children with ocular allergy.. Children with history of AC were classified to seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The clinical history and outcome of treatment were recorded.. One hundred and sixty-four children were recruited. PAC was the most common type (61.6%), followed by SAC (21.3%), VKC (12.2%), and AKC (4.9%). Male preponderance was found in all groups. Mean age of onset was 6.8 ± 2.8 years. Allergic rhinitis was the most common co-morbidity (97.6%). The common sensitized allergen is house-dust mites (86.1%). Standard treatments in all groups were natural tear and topical olopatadine. Add-on medications were usually needed in severe types of AC (VKC, AKC). History of topical corticosteroid use was 68.8% and 12.5% in VKC and AKC, respectively. All of them can discontinue topical corticosteroid when topical tacrolimus was applied. The overall remission was found 35% in VKC group and 63% in AKC group. The median duration of treatment was 20.5 months in VKC group and 11 months in AKC group.. most Thai children with AC sensitized to house-dust mites. In severe forms of AC, most patients needed addon medication. The use of topical calcineurin inhibitor as an add-on therapy can decrease the use of topical corticosteroid.

Topics: Allergens; Child; Child, Preschool; Chronic Disease; Conjunctivitis, Allergic; Dust; Humans; Male; Southeast Asian People; Tacrolimus

To compare the efficacy of 2% rebamipide suspension with topical cyclosporine and tacrolimus for managing vernal keratoconjunctivitis (VKC).. In this prospective, interventional study, 38 patients with moderate to severe VKC were allocated to receive either 2% rebamipide in one eye and 0.03% tacrolimus ointment in the contralateral eye (n = 19) or 2% rebamipide in one eye and 0.05% cyclosporine in the contralateral eye (n = 19) for 12 weeks. Ten ocular signs and 7 symptoms were graded on a scale of 0-3 each for each eye at every visit.. Total sign and symptom scores reduced significantly in all 4 subgroups (all p's <0.05) at 12 weeks. Reduction of mean sign scores between rebamipide and tacrolimus (- 4.67 ± 4.63 and - 2.80 ± 3.18 respectively) and between rebamipide and cyclosporine (-6.00 ± 3.74 and -5.42 ± 3.68 respectively) was comparable. Reduction in symptom scores was also comparable between subgroups.. Our findings suggest that efficacy of topical rebamipide is comparable to topical cyclosporine and tacrolimus for managing moderate to severe VKC and it merits further evaluation as a novel steroid sparing alternative for this disorder.

Topics: Administration, Topical; Alanine; Conjunctivitis, Allergic; Cyclosporine; Humans; Immunologic Factors; Immunosuppressive Agents; Ointments; Ophthalmic Solutions; Prospective Studies; Quinolones; Tacrolimus; Treatment Outcome

To compare the effects of ciclosporine A (2%) eye drop and tacrolimus (0.03%) eye ointment on children with vernal keratoconjunctivitis (VKC) who were not responding to corticosteroid eye drops.. A prospective comparative study was carried out on children who were diagnosed with refractory VKC at the ophthalmology clinic in Benha University, Delta area, Egypt, during the period from October 2019 to February 2020.. Fifty-nine patients completed this study. Regarding the individual symptom score, redness, burning, photophobia, and foreign body sensation were significantly reduced in the tacrolimus group compared to those in the ciclosporine A group during the 1st week (p < 0.05). Moreover, the tacrolimus group showed a statistically significant reduction in burning and foreign body sensation at the 4th week (both p = 0.032), and in redness and burning sensation at the 12th week compared to those in the ciclosporine A group (p = 0.005 and 0.048, respectively). The tacrolimus group showed significantly lower mean scores for tarsal conjunctival papillary hypertrophy at the 1st week and 12th week (p = 0.037 and 0.046, respectively), and for punctate erosion and cobblestone papillae at the 1st week (p = 0.029 and 0.037, respectively) than the ciclosporine group. Failure of treatment was observed in 6 patients (19.35%) in the ciclosporine A group and in 5 patients (17.85%) in the tacrolimus group. No serious side effects were detected in any group.. A higher reduction in inflammatory symptoms and signs as well as compliance with tacrolimus 0.03% eye ointment than with ciclosporine A 2% eye drops was observed. Moreover, long-term medication for refractory cases is needed to control inflammation. Overall, our finding suggested that ciclosporine A eye drops and tacrolimus eye ointment could be considered as corticosteroid-sparing drugs in the management of children with refractory VKC.

Topics: Child; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Ointments; Ophthalmic Solutions; Prospective Studies; Tacrolimus; Treatment Outcome

The aim of this study was to evaluate the safety and efficacy of tacrolimus 0.1% eye drops in a large population of pediatric patients affected by a severe form of vernal keratoconjunctivitis (VKC) who responded poorly to cyclosporine eye drops.. This is a retrospective study based on standardized clinical charts and data collection of consecutive patients affected by severe VKC who responded poorly to cyclosporine eye drops topical treatment but treated with tacrolimus 0.1% eye drops with a follow-up of 18 months. Four clinical signs were graded for analysis: hyperemia, tarsal papillae, giant papillae, and limbal papillae. The blood tests for kidney and liver function and the tacrolimus level were studied. Visits were scheduled at baseline and at 3, 6, 12, and 18 months. Patients received tacrolimus 0.1% eye drops in both eyes 2 times daily.. Four hundred thirty-one patients were included. Three hundred twenty-five patients were affected by a seasonal form, whereas the remaining 106 by a perennial form. Statistical analysis on each single score showed a positive relevance (P < 0.001) from baseline to all other visits. No local or systemic complications were recorded.. Tacrolimus has been proposed as a treatment for severe forms of VKC. This study has confirmed the safety and efficacy of tacrolimus 0.1% eye drops in a large pediatric population of patients affected by a severe form of VKC who responded poorly to cyclosporine eye drops.

Topics: Adolescent; Child; Child, Preschool; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Retrospective Studies; Tacrolimus; Treatment Outcome

Children with vernal keratoconjunctivitis (VKC) present symptoms that are similar to other ocular allergies, but more pronounced, and are controlled using topical steroids. To avoid excessive and prolonged use of topical steroid eye drops, over the past 20 years galenic eye drops of cyclosporine with a concentration of 1% to 2% and tacrolimus with a concentration of 0.1% have been introduced as a treatment for the severe and unresponsive forms. The main symptoms of VKC occur most frequently during the spring and tend to get worse during the summer, meaning that affected children tend to avoid exposure to sunlight. The aim of this study was to assess the most common cell types present in the conjunctiva of children with VKC, how ocular treatment can influence them, and whether affected children express a typical conjunctival pattern, which could be useful as a pathognomonic pattern of VKC, allowing us to study this rare eye disease.. This was a cohort study of 56 children, of whom 17 were not receiving any treatment at the time of testing, 14 were using steroid eye drops or had taken them in the previous 10 days, and 25 were treated with cyclosporine eye drops or tacrolimus eye drops 0.1%.. Children in group 1 (no topical therapy) express more epithelial cells, neutrophils, mast cells, eosinophils, and lymphocytes than the other two groups.. Given the ease of performance, when conducting further longitudinal studies, the conjunctival cytology examination could be used, on the one hand, to diagnose VKC, especially when the clinical diagnosis is uncertain, and, on the other, to follow disease evolution and monitor the response to topical treatment.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Conjunctiva; Conjunctivitis, Allergic; Cyclosporine; Cytological Techniques; Female; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Tacrolimus

Topics: Adolescent; Aged; Child; Conjunctivitis, Allergic; Drug Resistance; Female; Gene Expression Profiling; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Male; Middle Aged; Sequence Analysis, RNA; Tacrolimus; Transcriptome

Severe atopic keratoconjunctivitis (AKC) is a relatively rare disease, and some cases are refractory to conventional steroid treatment.. To examine the efficacy of 0.1% tacrolimus ophthalmic suspension in treating severe AKC during a 1-year follow-up.. This was a single-center, retrospective clinical study. Sixty eyes from 30 patients with severe AKC who were treated with 0.1% tacrolimus ophthalmic suspension 4 times per day, were included. The mean age of the patients was 21.5 ± 13.7 years. The severity of objective signs was observed at baseline (before treatment), at 2 weeks, and at 1, 2, 3, 6, and 12 months after treatment initiation. Ten objective signs of palpebral conjunctiva, bulbar conjunctiva, limbus, and cornea were assessed using 4 grades (0 = normal; 1+ = mild; 2+ = moderate; 3+ = severe). Safety was assessed based on the incidence and the severity of adverse events.. The total score of the 10 clinical signs significantly decreased from baseline 2 weeks after initiating tacrolimus eye drop treatment, except at 2 months. The mean total score of clinical signs was 13.6 ± 6.6 at the beginning of treatment, and decreased to 5.4 ± 4.8 12 months after initiation. Treatment was gradually tapered, with increasing intervals between applications. Additional medications were required to provide relief in 18 patients during follow-up. No patient discontinued treatment due to adverse drug effects. Herpes keratitis was observed in 3 cases during follow-up. However, these cases were completely controlled.. The 0.1% tacrolimus ophthalmic suspension is effective for the treatment of severe AKC refractory to standard conventional treatments throughout a full year.

Topics: Adolescent; Adult; Child; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Male; Ophthalmic Solutions; Retrospective Studies; Severity of Illness Index; Tacrolimus; Treatment Outcome; Young Adult

To report the results of treating children with vernal keratoconjunctivitis (VKC) using a monotherapy of topical tacrolimus 0.03%.. This was a prospective, nonrandomized observational study of children newly diagnosed with VKC. The severity of the disease was graded on a 4-point scale of symptoms and signs. Patients were treated with tacrolimus 0.03% ointment and were followed for 8 months according to a schedule based on the severity of the disease. The primary measure of treatment efficacy was the change in the score of objective signs. The incidence and severity of adverse events, if any, were recorded.. A total of 45 children aged 5-15 years were enrolled. The mean composite symptom score was 6.84 ± 2.26 at baseline and 0.71 ± 1.62 at 8 months, a statistically significant reduction (P < 0.001). The mean composite sign score was 9.6 ± 3.14 at baseline and 1.16 ± 1.28 at 8 months, also a statistically significant reduction (P < 0.001). Four patients had to be started on steroids within the first month of treatment and were considered treatment failures. Thus, 89% of patients showed significant improvement. No participant experienced adverse effects, although some reported a transient stinging sensation.. In our study cohort topical tacrolimus ointment 0.03% as a monotherapy for VKC was successful in the majority of subjects, and there was no adverse effect.

Topics: Administration, Topical; Adolescent; Child; Child, Preschool; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Prospective Studies; Tacrolimus; Treatment Outcome

Atopic keratoconjunctivitis is frequently associated with atopic eyelid dermatitis. It may require topical steroids, the prolonged use of which may cause ocular complications. Tacrolimus is an immunosuppressant used topically on the skin in atopic dermatitis. The purpose of this study is to evaluate the efficacy and tolerability of tacrolimus 0.1% ointment applied to the eyelids in atopic keratoconjunctivitis.. This is a single center, retrospective study carried out between June 2014 and February 2017. Patients presenting with atopic keratoconjunctivitis uncontrolled by first-line medical treatment were included. The main outcome was change in functional symptoms as evaluated by the NEI-VFQ25 and OSDI quality of life scores. Secondary criteria were visual acuity and topical steroids use.. Among the 18 patients included, the mean age was 37.9±16.8years. The first follow-up visit occurred on average 68.3±55.3 days after initiation of treatment. The NEI-VFQ25 score improved significantly for seven of the sub-scores (P<0.05), and the mean OSDI decreased significantly from 52.3±26.2 to 22.0±27.0 (P<0.001), demonstrating a decrease in ocular symptoms. A significant reduction in the number of patients requiring topical steroid treatment was observed. There was no significant change in visual acuity.. Tacrolimus 0.1% ointment applied to the eyelids appears to be an effective treatment in the management of atopic keratoconjunctivitis.

Topics: Administration, Topical; Adult; Conjunctivitis, Allergic; Dermatitis, Atopic; Female; Humans; Keratoconjunctivitis; Male; Middle Aged; Ointments; Retrospective Studies; Tacrolimus; Treatment Outcome; Young Adult

The study aims to evaluate the therapeutic effects of dermatologic tacrolimus ointment on eyelids to treat refractory vernal keratoconjunctivitis (VKC).. This institutional study examined the effects of steroid treatment for 10 patients diagnosed with severe VKC refractory to steroid treatment. Patients received 0.1% dermatologic topical tacrolimus treatment on their eyelids once or twice daily for concomitant atopic dermatitis. The therapeutic outcomes were evaluated according to change in severity of clinical findings recorded with serial external ocular photography and change in requirement for steroid treatment.. Clinical signs and symptoms improved substantially after tacrolimus treatment. Significant reduction in size of papillae, decrease of discharge, improvement in hyperemia, and shield ulcer healing with re-epithelization were observed in all patients. Six out of 10 (60%) patients did not receive steroid treatment. Long-term maintenance of tacrolimus was required to prevent episodic exacerbation. Patients' only treatment-related complaints were of mild burning sensations during medication application to eyelids, and this sensation disappeared a few days after treatment.. Application of 0.1% dermatologic tacrolimus ointment to eyelids is effective and safe in the treatment of refractory VKC in patients with concomitant atopic dermatitis. This treatment may serve as a substitute for or decrease the requirement of steroid treatment.

Topics: Administration, Topical; Adolescent; Child; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Drug Resistance; Eyelids; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Ointments; Retrospective Studies; Tacrolimus; Treatment Outcome

Atopic keratoconjunctivitis is associated with eyelid eczema. It may require the use of local corticosteroids which if prolonged can be a source of ocular complications. Tacrolimus is an immunosuppressant used in cutaneous application in atopic dermatitis. The aim of this study was to measure the efficacy and tolerance of tacrolimus 0.1% ointment in palpebral application in atopic keratoconjunctivitis.. This retrospective, single-center study was conducted between June 2014 and February 2017. Patients with atopic keratoconjunctivitis not controlled by first-line medical treatments were included. The primary endpoint was the evolution of functional signs as assessed by the NEI-VFQ25 and OSDI quality of life scores. Secondary endpoints were visual acuity and local corticosteroid use.. Among the 18 patients included, the mean age was 37.9±16.8 years. The first follow-up visit was on average 68.3±55.3 days after initiation of treatment. The NEI-VFQ25 score was significantly improved for seven of its sub-scores (P<0.05) and the mean OSDI decreased significantly from 52.3±26.2 to 22.0±27.0 (P<0.001) showing a decrease in eye discomfort. A significant reduction was observed in the number of patients using local corticosteroids. There was no significant change in visual acuity.. Tacrolimus ointment 0.1% in palpebral application appears to be an effective treatment for the management of atopic keratoconjunctivitis.

Topics: Administration, Topical; Adult; Conjunctivitis, Allergic; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Male; Middle Aged; Ointments; Retrospective Studies; Tacrolimus; Treatment Outcome; Young Adult

Topics: Administration, Ophthalmic; Adolescent; Adult; Chronic Disease; Conjunctivitis, Allergic; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Prospective Studies; Tacrolimus; Treatment Outcome; Young Adult

The purpose of this study was to evaluate the efficacy and safety of 0.1% tacrolimus eye drops in the tarsal form of vernal keratoconjunctivitis (VKC) and to survey the changes of dendritic cells at the palpebral conjunctiva in patients with VKC by in vivo confocal microscopy.. A total of 17 patients (34 eyes) with the tarsal form of VKC were enrolled in this prospective, nonrandomized case series. They were treated with 0.1% tacrolimus eye drops twice daily after discontinuation of all other topical medications. Subjective ocular symptoms and objective ocular signs were scored on a 4-point scale by one ophthalmologist and the characteristics of the dendritic cells in each right eye at the palpebral conjunctiva were evaluated by in vivo confocal microscopy before treatment and at the 1st, 2th, 4th, and 8th weeks after treatment.. After 1 week of treatment with 0.1% tacrolimus eye drops, the score for each symptom in all patients showed a significant (p < 0.001) improvement, and 13 patients (76%) experienced dramatic relief of symptoms. In addition, there was a significantly (p < 0.001) decreased clinical sign score (except for giant papillae) after 4 weeks, and a significant (p < 0.001) improvement in the score of giant papillae after 8 weeks of treatment. The characteristics of dendritic cells (including cell count, total area, average size, perimeter, and diameter) showed a significant (p < 0.05) decrease after 2 weeks of treatment. During the follow-up, no other topical medications were required and no significant changes in visual acuity were documented. No cataracts or elevation of intraocular pressures were detected. Only 5 patients (29%) had a tingling or burning sensation or discomfort.. Tacrolimus 0.1% eye drops are an effective and safe treatment for the tarsal form of VKC, and can rapidly inhibit the activity of dendritic cells, improve symptoms, reduce papillary hyperplasia, and reverse damage at the palpebral conjunctiva. The side effects could affect the compliance of some patients.

Topics: Adolescent; Adult; Child; Conjunctiva; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Prospective Studies; Tacrolimus; Treatment Outcome; Young Adult

Topics: Conjunctivitis, Allergic; Double-Blind Method; Humans; Immunosuppressive Agents; Interferon-alpha; Ophthalmic Solutions; Tacrolimus

To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-ε-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model.. The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed.. The microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De, and Te+De groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group.. Tacrolimus-loaded microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

Topics: Absorbable Implants; Allergens; Ambrosia; Animals; CD11c Antigen; CD4 Antigens; Conjunctivitis, Allergic; Delayed-Action Preparations; Disease Models, Animal; Drug Delivery Systems; Immunohistochemistry; Immunosuppressive Agents; Interleukin-4; Mice; Mice, Inbred BALB C; Polyesters; Polyethylene Glycols; Tacrolimus

To evaluate galectin-3 (Gal-3), a β-galactoside binding protein, as a possible biomarker in ocular allergy and further investigated the role of endogenous Gal-3 in a murine model of ovalbumin (OVA)-induced allergic conjunctivitis (AC).. Conjunctival impression cytology specimens from control and patients with severe vernal keratoconjunctivitis, treated or untreated, were used to evaluate Gal-3 expression by immunocytochemistry. To investigate the mechanism of action of Gal-3, OVA-immunised BALB/c male wild-type (WT) and Gal-3 null (Gal-3. Patients with AC and OVA-sensitised WT mice exhibited increased levels of Gal-3 in the conjunctiva compared with control, an effect reverted by the action of Dex and TC therapy. Twenty-four hours after the final OVA challenge, total and anti-OVA IgE levels increased significantly in the blood of OVA-sensitised WT and Gal-3. Gal-3 contributes to the pathogenesis of ocular allergy and represents a relevant therapeutic target.

Topics: Adolescent; Adult; Animals; Anti-Allergic Agents; Biomarkers; Blood Proteins; Blotting, Western; Child; Conjunctivitis, Allergic; Disease Models, Animal; Drug Therapy, Combination; Female; Galectin 3; Galectins; Glucocorticoids; Humans; Immunoenzyme Techniques; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Tacrolimus

Allergic conjunctival granuloma is a rare cause of conjunctival ocular lesions. The aim of this case report was to present a successful treatment of an allergic conjunctival granuloma with topical tacrolimus eye drops. A 20-year-old female presented with bilateral multiple yellow nodules of the bulbar conjunctival epithelium and conjunctival injection. The patient had tearing, photophobia, itching, foreign body sensation, and red eye. The patient's signs and symptoms progressed despite the use of topical steroids. The patient was treated by application of tacrolimus eye drop (0.005%) in her right eye every 6 h while the left eye was put on placebo. Her signs and symptoms were recorded at each visit. After 3 weeks' therapy with topical tacrolimus eye drop, the patient became asymptomatic in her right eye and conjunctival granulomas fully resolved. Topical tacrolimus seems to be an effective therapeutic option for the treatment of allergic conjunctival granulomas.

Topics: Administration, Ophthalmic; Conjunctivitis, Allergic; Female; Granuloma; Humans; Immunosuppressive Agents; Ophthalmic Solutions; Tacrolimus; Young Adult

Atopic keratoconjunctivitis (AKC) remains a difficult diagnosis despite advances in imaging technologies. This is a case study of the diagnostic and treatment course for a patient with AKC.. A 15-year-old male complained of progressively increasing pain, redness, watering and blurred vision in the right eye. The medical history showed that the patient suffered from itching on the hands, knees, neck and the eye skin one year before the onset of initial symptoms in the affected eye.. A final diagnosis of stage III AKC with atopic dermatitis (AD) was reached.. The patient was used 0.1% tacrolimus eye drops and 0.3% gatifloxacin eye gel after antimicrobial susceptibility test was performed. In the presence of AD, 0.1% mometasone furoate cream and 0.03% tacrolimus ointment were applied twice daily.. One month after starting treatment, the conjunctivitis and corneal ulcer rapidly improved along with reduced lid papillae. Macular grade corneal opacity was noticed with minimal thinning. The AD also rapidly improved. At the end of two months patient was asymptomatic with a significant improvement in his quality of life.. Proper diagnosis of AKC especially when associated with dermatological signs along with management of AD in conjunction with dermatologist is necessary to prevent corneal involvement which can cause permanent visual disability is of utmost importance. We also noticed that topical tacrolimus is a good option for the treatment of severe AKC with AD along with systemic immunosupressants.

Topics: Administration, Topical; Adolescent; Anti-Allergic Agents; Anti-Bacterial Agents; Conjunctivitis, Allergic; Corneal Ulcer; Dermatitis, Atopic; Fluoroquinolones; Gatifloxacin; Humans; Immunosuppressive Agents; Male; Mometasone Furoate; Ophthalmic Solutions; Tacrolimus; Treatment Outcome

Topics: Child; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Male; Prospective Studies; Tacrolimus

Marine polysaccharide-based nanomaterial attracted considerable attention due to its biocompatibility and biodegradability. Here, a novel polymannuronic acid derivative (PM-C

Topics: Alginates; Amines; Animals; Cell Line; Conjunctivitis, Allergic; Drug Carriers; Drug Liberation; Glucuronic Acid; Hexuronic Acids; Mice; Micelles; Tacrolimus

To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases.. Open cohort study.. Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791).. The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics.. Changes in the corneal epitheliopathy score.. Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus.. The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids.

Topics: Administration, Oral; Administration, Topical; Adolescent; Betamethasone; Calcineurin Inhibitors; Child; Cohort Studies; Conjunctivitis, Allergic; Corneal Ulcer; Drug Therapy, Combination; Epithelium, Corneal; Female; Fluorometholone; Glucocorticoids; Humans; Male; Ophthalmic Solutions; Retrospective Studies; Tacrolimus; Young Adult

Vernal keratoconjunctivitis is an ocular allergy that is common in the pediatric age group. It is often chronic, severe, and nonresponsive to the available treatment options. Management of these children is difficult and often a dilemma for the practitioner. There is a need to simplify and standardize its management. To achieve this goal, we require a grading system to judge the severity of inflammation and an algorithm to select the appropriate medications. This article provides a simple and practically useful grading system and a stepladder algorithm for systematic treatment of these patients. Use of appropriate treatment modalities can reduce treatment and disease-related complications.

Topics: Algorithms; Conjunctivitis, Allergic; Cyclosporine; Drug Combinations; Humans; Immunosuppressive Agents; Ophthalmic Solutions; Severity of Illness Index; Tacrolimus

To evaluate the efficacy of 0.03% tacrolimus in the treatment of corticosteroid-refractory vernal keratoconjunctivitis (VKC).. This open-label study enrolled 30 patients with VKC who were not responding to topical corticosteroid treatment for at least 4 weeks. All patients were treated with 0.03% tacrolimus eye ointment 3 times daily, 0.05% ketotifen eye drops twice daily, and preservative-free artificial tears. Symptoms (itching, redness, watering, discharge, burning, and photophobia) and signs (conjunctival injection, papillae, cobblestone papillae, limbal inflammation, or hypertrophy and corneal epithelial staining) were graded on a 4-point scale at enrolment, after 4 weeks, and at the end of treatment period, which was at 12 weeks. Composite scores for symptoms and signs were computed by summing individual scores. Treatment failure was denoted if additional treatment with corticosteroids were required.. The composite scores for symptoms (10.8, 3.8, 3.4) and signs (8.7, 4.7, 4.0) in 23 patients showed a statistically significant (P < 0.05) improvement from baseline to the 4- and 12-week visits. Among the signs, upper tarsal papilla showed improvement only at 12 weeks, but the scores for giant cobblestone papillae did not reach statistically significant reduction even at 12 weeks. There was improvement in visual acuity at 12 weeks, although it was not statistically significant (P = 0.05). Treatment failure was recorded in 17% patients. The only adverse effect reported was transient stinging sensation lasting for a few days.. Tacrolimus 0.03% was apparently safe and effective in treating patients with steroid-refractory VKC. A small subset of patients may still require supplemental topical corticosteroids for resolution of their symptoms.

Topics: Administration, Topical; Adolescent; Child; Child, Preschool; Conjunctivitis, Allergic; Drug Resistance; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Ointments; Tacrolimus; Treatment Outcome; Visual Acuity; Young Adult

To evaluate the long-term clinical outcomes of 0.1% tacrolimus dermatologic ointment (Protopic) in cases of refractory atopic keratoconjunctivitis (AKC).. Prospective, nonrandomized, noncontrolled case series.. Twenty-two eyes from 11 patients with severe AKC who were treated with 0.1% tacrolimus ointment were followed prospectively. The mean age of the patients was 32.27 ± 12.7 years (range, 19-61 years). Each patient completed a follow-up period of at least 48 months, during which the signs and symptoms of AKC were assessed. Changes in the total scores of signs and symptoms from baseline were recorded at each visit, and the main outcome measure was the clinical response to topical tacrolimus treatment.. Dramatic improvements in clinical signs and symptoms were achieved 1 week after starting topical tacrolimus treatment, and complete clinical resolution was observed in almost all patients 6 weeks after starting treatment. Treatment was gradually reduced, with increasing intervals between applications. Eight patients remained asymptomatic for up to 3 years, although recurrence occurred in 3 patients who attempted to discontinue treatment. All patients complained of a mild burning sensation upon application of the ointment. No additional medications were required to provide relief, and no patient discontinued treatment because of adverse drug effects. No drug-related ocular complications were encountered, and no significant changes in visual acuity or refraction were documented.. Tacrolimus dermatologic ointment is a potentially safe and effective treatment for AKC cases refractory to standard treatment and may substitute for steroid treatments aimed at controlling disease activity.

Topics: Adult; Conjunctivitis, Allergic; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Prospective Studies; Recurrence; Tacrolimus; Treatment Outcome; Visual Acuity; Young Adult

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

The objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement.. This prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during the study period. Ten clinical signs and six clinical symptoms were rated on a four-grade scale. The primary endpoint was the change from baseline in total clinical signs and symptoms score at the last observation or following 6 months of treatment.. Total signs and symptoms score significantly decreased after 1 month of treatment (p<0.001). Giant papillae and corneal lesions were also reduced by tacrolimus eye drop use (p<0.001). The drug proved effective in patients whose condition did not respond well to topical cyclosporine therapy. About 50% of all patients using topical steroids were weaned. The most common adverse reaction was a transient burning sensation (3.20%).. Tacrolimus eye drops are highly effective in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement, and may reduce or replace topical steroid use.. UMIN 000008640.

Topics: Adolescent; Adult; Child; Conjunctivitis, Allergic; Corneal Diseases; Female; Humans; Immunosuppressive Agents; Male; Ophthalmic Solutions; Prospective Studies; Tacrolimus; Young Adult

A retrospective study for evaluating the clinical course of patients with vernal keratoconjunctivitis (VKC) treated with topical tacrolimus ophthalmic suspension 0.1% (Tacrolimus).. Subjects were 30 patients (24 men and 6 women) with VKC who were treated with a combined therapy of Tacrolimus and antiallergic ophthalmic solution, and could be followed up for six months. The subjects were divided into two groups: 1. A conversion treatment group in which Tacrolimus was substituted for a steroid ophthalmic solution [21 patients; average age 14.7 +/- 9.44 years (mean +/- SD)] and 2. An additional treatment group receiving Tacrolimus and anti-allergic ophthalmic solution [9 patients; average age 28.2 +/- 7.31 years (mean +/- SD)]. The therapeutic effects of the patients were evaluated chronologically using the ocular clinical score according to the papillae-limbus-cornea grading score and eosinophil cationic protein (ECP) levels in tears.. Papillae-limbus-cornea grading scores were significantly decreased from 8 (median) points at instillation initiation to 5 points at the first month after initiation of Tacrolimus treatment (p < 0.01, Steel test). Tear ECP levels were significantly decreased from 3493.6 (median) ng/ml at instillation initiation to 205.6 ng/ml at the first month after initiation of Tacrolimus treatment (p < 0.05, Steel test). During the course, four cases of exacerbation were found among the 30 cases, but no infections of the anterior segment were found.. The therapeutic effect of Tacrolimus eye drops for vernal keratoconjunctivitis was remarkable at one month after instillation initiation. For evaluating the effect of treatment and diagnosing exacerbation in VKC treated with Tacrolimus, a follow-up examination using clinical indexes such as the papillae-limbus-cornea grading score and ECP levels in tears is beneficial.

Topics: Adolescent; Adult; Anti-Allergic Agents; Conjunctivitis, Allergic; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Retrospective Studies; Tacrolimus; Treatment Outcome

Acute allergic conjunctivitis is a constantly challenging condition that often requires steroids for effective management. Alternative treatment options are needed due to the potential side effects of steroids. Tacrolimus has been used for vernal/atopic conjunctivitis. The aim of our study was to investigate the therapeutic effect of topical administration of 0.03 % tacrolimus (eye drops or ointment) in comparison to 0.1 % dexamethasone in a mouse model of acute allergic conjunctivitis.. BALB/c mice were sensitized by an intraperitoneal injection of 10 μg/0.2 ml ovalbumin (OVA) absorbed on ALUM (2.0 mg) on days 1 and 8. They were challenged by topical instillation of 2 μl of 15 % OVA (absorbed in 10 % glycerol) twice daily, on days 15-21. Treatment was administered twice daily on days 17-21. Mice were randomly assigned topical treatment groups: Group 1, 0.1 % dexamethasone drops; Group 2, 0.03 % tacrolimus drops; Group 3, 0.03 % tacrolimus ointment; Group 4 PBS drops (control). On day 22 all mice underwent clinical evaluation, blood sampling for IgE levels, and conjunctivas were removed for eosinophil counting.. IgE and OVA-specific IgE levels were similar among all groups, demonstrating induction of allergic reaction in all mice. Significantly lower clinical scores were found among all treated groups as compared to controls (P < 0.001), while no significant difference was found among the three treatment groups (P > 0.05). Conjunctival eosinophil counts were significantly lower in Group 1 (P < 0.05) as compared to the other groups.. The clinical efficacy of topical 0.03 % tacrolimus was similar to 0.1 % dexamethasone for acute allergic conjunctivitis.

Topics: Acute Disease; Administration, Topical; Animals; Conjunctivitis, Allergic; Dexamethasone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Glucocorticoids; Immunoglobulin E; Immunosuppressive Agents; Injections, Intraperitoneal; Mice; Ophthalmic Solutions; Ovalbumin; Tacrolimus; Treatment Outcome

Topics: Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Keratoconjunctivitis; Tacrolimus

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

To evaluate the long-term effectiveness of the combination of topical cyclosporine drops and tacrolimus ointment in the treatment of steroid-dependent atopic keratoconjunctivitis (AKC).. Ten patients with moderate to severe AKC participated in the study. Topical cyclosporine 0.05% was used, as a monotherapy, 6 times daily during the first month of the study, followed by 4 times daily during the second month. The patients were then instructed to self-treat with topical cyclosporine at a dose ranging from 2 to 6 times daily depending on the severity of the disease. Tacrolimus ointment 0.03% was applied on the lid skin. Follow-up examinations were performed approximately every 3 months. Each patient completed a follow-up period of at least 12 months. Symptoms and signs of AKC were assessed on the day of enrollment, on days 28, 56, and 63, and at subsequent follow-up visits. Flare-ups of AKC requiring steroid use and progression of the disease findings were also recorded.. All patients experienced significant improvement of their symptoms and signs during the first 2 months of the study. Two patients were lost to follow-up after the initial 2 months. One patient was noncompliant and continued the treatment only for 7 months. During the median treatment period of 21.5 months for the 7 continuing patients, a total of only 2 flare-up episodes were noted requiring topical steroids.. Adequate topical immunomodulation using topical calcineurin inhibitors may eliminate the need for steroids and favorably alter the long-term prognosis of patients with AKC.

Topics: Administration, Topical; Adult; Calcineurin Inhibitors; Conjunctivitis, Allergic; Cyclosporine; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Ophthalmic Solutions; Prednisolone; Prospective Studies; Tacrolimus; Treatment Outcome; Visual Acuity; Young Adult

To determine whether topical tacrolimus might prove effective in the treatment of refractory anterior segment inflammatory diseases, and to evaluate its efficacy in eyes with ocular graft versus host disease (GVHD), and vernal keratoconjunctivitis (VKC).. Twenty-eight eyes of 14 patients with anterior segment inflammation refractory to steroid treatment were treated with 0.03% tacrolimus ointment at the Samsung Medical Center, Seoul, Korea from March 2008 through August 2009. Seven patients had ocular GVHD and seven had VKC. We evaluated the conjunctival and corneal inflammatory change at one, two, four, and eight weeks after treatment with a scoring system. Time to initial response of treatment and therapeutic effect between GVHD and VKC was also analyzed. After the eight-week treatment period, patients were divided into two groups (maintenance group and discontinuance group). Eight patients maintained the treatment for an additional four months, and six patients discontinued the treatments. Therapeutic effect was also compared between the groups at eight weeks and six months after treatment.. The mean conjunctival and corneal inflammation score was reduced significantly at eight weeks after treatment (p < 0.0001). The therapeutic effect in conjunctival inflammation was first noted at week two after the initial treatment (p = 0.002); reduction in corneal inflammation was first noted at one week (p = 0.0009). When compared according to diagnosis, no therapeutic difference was detected between the groups (p > 0.05). Six months after treatment, we noted no therapeutic differences between the maintenance group and discontinuance group (p > 0.05).. 0.03% tacrolimus ointment was safe and effective for use in anterior segment inflammatory disease refractory to steroid.

Topics: Administration, Topical; Adolescent; Adult; Child; Conjunctivitis, Allergic; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Prospective Studies; Statistics, Nonparametric; 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

To evaluate the efficacy and safety of topical 0.005% tacrolimus eye drop for treatment of refractory vernal keratoconjunctivitis (VKC).. This prospective study included 20 eyes of 10 patients with refractory VKC, who had active symptomatic disease despite conventional medications including topical steroids. After discontinuing all other medications, patients were treated with topical 0.005% tacrolimus eye drop four times a day. Changes in subjective symptoms and objective signs after treatment were evaluated, and development of possible complications was assessed.. Mean age of patients was 21.3±7.4 years and mean duration of VKC was 12.1±5.8 years. After starting tacrolimus eye drop, patients were followed for a mean duration of 10.7±3.7 months (range, 6-15 months). All symptoms including itching, redness, photosensitivity, foreign body sensation, and mucus discharge improved after the treatment; itching was the first symptom to show dramatic relief. In addition, there was improvement in objective signs including conjunctival hyperaemia, conjunctival papillary hypertrophy, giant papillae, limbal hypertrophy, corneal punctate epithelial erosions, and corneal pannus; conjunctival hyperaemia was the first sign to show improvement. No patient required addition of other medications including steroids for further relief. Any attempt to discontinue tacrolimus eye drop was associated with recurrence of patients' symptoms and signs, necessitating continued use of the medication during the entire follow-up time. No ocular complication related to tacrolimus was noted.. Topical 0.005% tacrolimus eye drop seemed to be a safe and effective treatment for steroid-resistant refractory VKC; however, long-term use was needed to control the disease.

Topics: Adolescent; Adult; Child; Conjunctivitis, Allergic; Female; Humans; Hyperemia; Immunosuppressive Agents; Male; Ophthalmic Solutions; Prospective Studies; Seasons; Tacrolimus; Visual Acuity; Young Adult

To examine the clinical efficacy and anti-inflammatory effects of tacrolimus eye drops; we studied the changes in clinical ocular findings and measured tear eosinophil cationic protein (ECP) levels of atopic keratoconjunctivitis (AKC) patients before and after the treatment.. Nine eyes of 9 patients (8 males, 1 female; mean age: 16.9 ± 11.4 years; range: 6-44 years) diagnosed with moderate or severe AKC disease were enrolled in this prospective study and treated with tacrolimus. All patients received 0.1% tacrolimus eye drops 2 times a day for 1 month. Tear samples were taken before and after treatment and ECP concentrations were obtained. Corneal fluorescein staining and conjunctival injection, edema, and papillary formation were graded on the recruitment day and one month later. Analysis of pre- and post-treatment findings was done using the Wilcoxon signed test. The ECP concentrations were correlated with the clinical signs using Spearman correlation tests.. Post-treatment tear ECP levels were significantly reduced compared to the pre-treatment level. Clinical corneal scores also improved significantly after one month treatment with tacrolimus eye-drops. The mean conjunctival injection and conjunctival edema scores were significantly (p<0.05) decreased after the drug therapy. Strong positive linear correlations between ECP values and clinical signs were observed. Patients did not present side effects during the treatment with tacrolimus.. In this pilot study, tacrolimus eye drops were found to reduce signs of AKC. ECP proved to correlate well with clinical signs of AKC.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Biomarkers; Child; Conjunctivitis, Allergic; Cornea; Corneal Edema; Drug Administration Schedule; Eosinophil Cationic Protein; Female; Fluorescein; Humans; Japan; Keratoconjunctivitis; Male; Ophthalmic Solutions; Prospective Studies; Tacrolimus; Tears; Treatment Outcome; Young Adult

To investigate, using tear fluid analysis, the effects of topical 0.1% tacrolims therapy on the pathophysiology of vernal keratoconjunctivitis (VKC).. Subjects were 6 eyes of 6 patients with VKC who underwent topical 0.1% tacrolims treatment twice a day and 5 eyes of 5 healthy volunteers as a control. Using the filter paper method, the tear fluid of the patients was sampled both before and 4 +/- 2 weeks after the treatment and once from the control subjects. Eosinophil cationic protein (ECP) in the tears was examined by the chemiimmunoluminescent enzyme immunoassay method and the chemokine profile of the tears was analyzed using an antibody-array.. In terms of the chemokine profile, growth related oncogene (GRO) -alpha, eotaxin-2 and thymus and activation-regulated chemokine (TARC) in the VKC were elevated compared with those in the controls, but they decreased significantly after the treatment (p<0.05). ECP concentrations in the tears were 3092 +/- 1658 ng/ml (average +/- S. D.) for the pretreatment base-line and 464 +/- 775 for the posttreatment. ECP values for the pre-treatment time were statistically significantly higher than those for the post-treatment in 5 patients (p<0.05).. Topical tacrolims treatment of VKC can suppress allergic inflammation associated chemokines such as eotaxin-2 and TARC.

Topics: Adolescent; Adult; Biomarkers; Chemokine CCL17; Chemokine CCL24; Chemokine CXCL1; Child; Conjunctivitis, Allergic; Depression, Chemical; Eosinophil Cationic Protein; Female; Humans; Immunoenzyme Techniques; Immunosuppressive Agents; Male; Protein Array Analysis; Tacrolimus; Tears; Young Adult

Topics: Administration, Topical; Child; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Male; Tacrolimus; Young Adult

Topics: Calcineurin Inhibitors; Conjunctivitis, Allergic; Cyclosporine; Humans; Ophthalmic Solutions; Tacrolimus

To evaluate the feasibility of tacrolimus 0.03% dermatological ointment (Protopic) in the treatment of intractable allergic conjunctivitis.. Twenty patients (mean age 10.8 years, range 6-26) with intractable allergic conjunctivitis were enrolled in an open-label study. Tacrolimus 0.03% ointment was applied into the conjunctival sac of both eyes twice daily for 8 weeks, followed by a 2-week washout period. Other ocular medications were discontinued. Conjunctivitis severity was recorded with a composite subjective/objective score (chemosis, tarsal papillary size, corneal staining, tearing, itching, and photophobia) at baseline, week 8, and after washout. Tacrolimus blood levels were measured at 2 weeks.. Statistically significant improvement in all categories of the conjunctivitis score was observed between baseline and the week 8 examination (p < 0.001). Adverse events were limited to local burning in one patient who discontinued treatment. Blood tacrolimus levels were mostly undetectable.. Application of tacrolimus 0.03% dermatological ointment into the conjunctival sac appears to be effective, well tolerated, and safe in the treatment of allergic conjunctivitis refractory to traditional treatment.

Topics: Administration, Topical; Adolescent; Adult; Child; Conjunctivitis, Allergic; Feasibility Studies; Female; Humans; Immunosuppressive Agents; Male; Ointments; Pilot Projects; Prospective Studies; Tacrolimus; Treatment Outcome; Visual Acuity

Topical immunomodulators such as tacrolimus have revolutionized the treatment of atopic dermatitis. Because T lymphocytes are integral to the pathogenesis of atopic dermatitis, systemic treatment with T-lymphocyte signal transduction inhibitors should ameliorate both the dermatologic and ocular manifestations. We describe the successful treatment of 6 patients with severe atopic keratoconjunctivitis (AKC) resistant to conventional therapies.. Retrospective observational case series. The charts of patients with AKC assessed by 1 of the authors were reviewed to identify those treated with systemic T-cell signal transduction inhibitors. Visual acuities, previous treatments, and the response to systemic signal transduction inhibitors were observed and reported in 6 patients.. The patients had a mean duration of AKC of 21 years. Topical corticosteroids and antihistamines had failed to control signs and symptoms of the disease in all patients, and in some patients, systemic corticosteroids and topical cyclosporine were ineffective. Three patients were treated with systemic cyclosporine, and 3 were treated with systemic tacrolimus. One patient was subsequently treated with daclizumab in addition to tacrolimus. All 6 patients experienced complete remission of their AKC and an increase in visual acuity.. Selective systemic immunosuppression of T lymphocytes with cyclosporine or tacrolimus has proved effective in the treatment of both atopic dermatitis and atopic keratoconjunctivitis. We advocate the consideration of systemic therapy in cases that are resistant to conventional treatment to resolve inflammation and preserve vision. Further studies in this area are advocated.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Conjunctivitis, Allergic; Cyclosporine; Daclizumab; Drug Therapy, Combination; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Infusions, Intravenous; Male; Middle Aged; Retrospective Studies; Signal Transduction; T-Lymphocytes; Tacrolimus; Visual Acuity

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

To investigate the therapeutic effects of topical tacrolimus ointment on refractory ocular surface inflammatory diseases.. Retrospective interventional consecutive case series.. Ten consecutive patients with severe ocular surface inflammatory diseases who were suspected to be steroid responders (elevation of intraocular pressure [IOP]) or were refractory to standard steroid therapy were studied. One patient had peripheral ulcerative keratitis with impending corneal perforation, 1 had a Mooren's ulcer, 2 had scleroperikeratitis, 5 had atopic keratoconjunctivitis, and 1 had vernal keratoconjunctivitis.. The clinical findings and therapeutic responses after treatment with 0.02% topical tacrolimus ointment were determined by conventional ophthalmological examinations.. Resolution of the ocular surface diseases (e.g., decrease of hyperemia, ulceration, size of papillae) and IOP. The necessity to use steroids was also assessed.. In all cases, marked to moderate improvement was obtained, including suppression of the melting reaction of the inflamed cornea, remission of scleroperikeratitis, and reduction of a giant papilla and corneal epithelial defect in severe atopic keratoconjunctivitis. The elevated IOP was reduced in steroid responders after successful cessation of steroid therapy. No adverse side effect was noted for 2 to 26 months of continuous treatment.. Topical tacrolimus ointment is effective in treating refractory ocular surface inflammatory diseases and should be considered as an alternative to higher doses, steroid supplementation, or surgical intervention.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Conjunctivitis, Allergic; Corneal Ulcer; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Retrospective Studies; Scleritis; Tacrolimus; Treatment Outcome

To report a case of refractory giant papillary conjunctivitis (GPC) treated by using topical tacrolimus 0.03% ointment.. A 16-year-old white boy with a history of GPC was referred to our department for severe GPC with eye itching, tearing, photophobia, discharge, and blepharospasm. The patient had received previous treatments with antihistamines, mast cell stabilizers, topical corticosteroid ointments, and surgical resection-cryopexy of GPC that were ineffective.. Topical tacrolimus 0.03% ointment (Protopic; 0.5 cm) was applied into the lower fornix twice a day. An improvement of the patient's symptoms was observed during the first 5 days of therapy, and the GPC was resolved within 15 days. After 1 month of continued topical tacrolimus ointment treatment, there was no evidence of GPC. Topical tacrolimus was tapered during the next 2 months. Six months after treatment, there were no GPC findings, and no side effects were reported.. Topical tacrolimus 0.03% ointment for severe GPC, refractory to conventional therapy, appears to be an effective alternative treatment.

Topics: Administration, Topical; Adolescent; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Male; Ointments; Tacrolimus; Treatment Outcome

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

Severe atopic keratoconjunctivitis (AKC) forms part of the spectrum of allergic eye disease and is often refractory to conventional topical treatment. Topical cyclosporin A and tacrolimus have been shown to reduce immunologic activation, symptoms, and signs of patients suffering from AKC, but there are no reports on safety and efficacy of systemic tacrolimus for this condition.. We report on a retrospective study of 3 patients with severe AKC, where the disease did not respond to conventional therapy, and they were therefore treated with low-dose systemic tacrolimus for at least 1 year as an adjunct to their existing treatment.. There was a good clinical response in all patients to low-dose systemic tacrolimus, with a low incidence of side effects and no relapse of symptoms after discontinuation of treatment.. Low-dose systemic tacrolimus is a safe and effective treatment of some patients with severe AKC, which is refractory to conventional treatment. Such patients need careful monitoring for side effects, and the long-term benefits need to be assessed as part of a clinical trial.

Topics: Adult; Chemotherapy, Adjuvant; Conjunctivitis, Allergic; Female; Humans; Immunosuppressive Agents; Male; 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 describe the effects of topical tacrolimus treatment of severe atopic eyelid disease.. Interventional consecutive case series.. A description of clinical findings and therapeutic response for five consecutive adult patients (mean age, 56.2 years; range 44-62) treated with topical tacrolimus for severe atopic eyelid disease at one institution.. Five patients with bilateral atopic eyelid disease that was refractory to treatment with topical corticosteroids were treated with tacrolimus 0.03% ointment, applied to the affected eyelid skin of both eyes twice daily. Eyelid induration, erythema, and eczematous changes were substantially improved within 1 to 3 weeks after initiation of topical tacrolimus treatment in all patients. There was an associated decrease in ocular surface irritation and inflammatory signs in each of four patients who also had atopic keratoconjunctivitis. No adverse effect associated with tacrolimus treatment was noted during continued treatment for 5 to 14 months. All patients were able to discontinue longstanding use of topical corticosteroid drugs.. Application of topical tacrolimus on eyelid skin may be effective for treatment of severe atopic dermatitis of the eyelids, and may have secondary benefits for atopic keratoconjunctivitis. Topical tacrolimus may be used for at least 1 year without apparent adverse reaction in some patients, although the rate of adverse reaction cannot be determined from this small series.

Topics: Administration, Topical; Adult; Conjunctivitis, Allergic; Dermatitis, Atopic; Eyelid Diseases; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Tacrolimus

Topics: Animals; Conjunctivitis, Allergic; Humans; Immunosuppressive Agents; Tacrolimus

It is well-known that FK506 strongly inhibits cytokine production by T cells in vitro. However, less evidence is available from in vivo studies of ocular allergy.. To study the anti-inflammatory effect of FK506 eye drops on late and delayed-type responses in several animal models of ocular allergy.. Rats and guinea-pigs were sensitized with egg albumin (EA) in adjuvant and later challenged by topical EA application to their eyes to examine the late response. Biopsy specimens of conjunctiva were stained with haematoxylin-eosin or stained for T cells and eosinophils. In addition, rats, rabbits and guinea-pigs were sensitized with complete Freund's adjuvant and later challenged by injecting purified protein derivatives for the delayed-type response. Bulbar conjunctival oedema and hyperaemia were graded by score in rabbits, and Evans blue (EB) extravasation was measured in rats and guinea-pigs. FK506 (0.01-1%) and steroid (0.1%) eye drops were instilled in the eyes of animals several times, before and after challenge.. FK506 eye drops inhibited T cell and eosinophil infiltration in the late response and EB extravasation in the delayed-type response in rats. Also, they inhibited conjunctival oedema, hyperaemia and ocular mucus in the delayed-type response in rabbits. These effects were similar to those of steroid eye drops (betamethasone sodium phosphate, fluorometholone). FK506 eye drops also inhibited inflammatory cell infiltration, the loss of conjunctival epithelium and decrease of goblet cells in the late response as well as EB extravasation in the delayed-type response in guineapigs, a steroid-resistant species.. FK506 eye drops inhibit late and delayed-type responses in animal models of ocular allergy.

Topics: Animals; Conjunctivitis, Allergic; Disease Models, Animal; Dose-Response Relationship, Immunologic; Eosinophils; Glucocorticoids; Guinea Pigs; Hypersensitivity, Delayed; Immunosuppressive Agents; Male; Ophthalmic Solutions; Rabbits; Rats; Rats, Inbred BN; T-Lymphocytes; 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

A number of structurally different allergens trigger the release of mediators from basophils by cross-linking of IgE receptors. In this study, we analyzed the effects of cyclosporine A (CSA) and FK-506 on allergen-induced histamine release in human blood basophils obtained from birch- or grass-pollen-allergic donors (n = 12). Preincubation of basophils with CSA (0.003-3 microg/ml) or FK-506 (0.003-3 microg/ml) led to inhibition of histamine release induced by purified recombinant tree pollen allergens (r Bet v 1, r Bet v 2) and timothy grass pollen allergens (r Ph1 p 1, r Ph1 p 2, r Ph1 p 5). The effects of CSA and FK-506 were dose dependent, with IC50 values ranging between 0.03 and 0.3 microg/ml for both CSA and FK-506. Cyclosporine H, an inactive CSA analog, did not show any effect on allergen-induced histamine secretion. IgE dependency of the reaction was demonstrated in passive transfer experiments using highly enriched human basophils (> 95% pure) and specific IgE from a patient allergic to Bet v 2. In summary, our data show that CSA and FK-506 inhibit recombinant-allergen-induced histamine release from peripheral blood basophils in allergic donors.

Topics: Adult; Allergens; Asthma; Basophils; Conjunctivitis, Allergic; Cyclosporine; Female; Histamine Release; Humans; Immunization, Passive; Immunoglobulin E; Immunosuppressive Agents; In Vitro Techniques; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal; Tacrolimus

Basic and clinical studies on immunotherapy in immune-mediated ocular disorders, i.e. uveitis, allograft rejection in corneal transplantation and allergic conjunctivitis, were carried out using a variety of immunosuppressants, including immunophilin ligands (FK506 and cyclosporine). 1. In an animal model for uveitis, experimental autoimmune uveitis (EAU), immunophilin ligands were demonstrated in the rat and monkey to have unique immunological activities: (1) intense and prolonged suppression of EAU development, (2) therapeutic effects by treating animals only after disease onset, (3) selective suppression on cellular immune response to S-antigen, (4) induction of immunological tolerance and activation of antigen specific suppressor cells. Combination therapy with low doses of immunophilin ligand and other immunosuppressant was tested to achieve better effects with less side effects. A low dose of cyclosporine (2 mg/kg/day) with bucillamine (20 mg/kg/day) which suppresses antigen-presenting activity by macrophages caused much stronger suppression of EAU than the therapy with either cyclosporine or bucillamine alone. Similarly, a low dose of FK506 (0.1 mg/kg/day) with dexamethasone (0.01 mg/kg/day) caused stronger suppression of EAU. A multi-center clinical open trial of FK506 in refractory uveitis was carried out in Japan. A total of 40 cases of active uveitis in the posterior segment of the eye were treated with FK506 (0.05, 0.1 or 0.2 mg/kg/day) and the mean observation period was 26.2 +/- 12.4 weeks. FK506 therapy improved uveitis in 60% of all cases including 47% of patients resistant to previous therapy with cyclosporine. FK506 significantly suppressed the number of uveitis attacks in patients with Behçet's disease. As for the side effects, 22.5% of patients showed abnormal values of renal function on FK506. The trough level of FK506 in whole blood correlated with adverse side effects as well as with therapeutic effect on uveitis, and it should be maintained between 15 and 25 ng/ml. 2. Effects of immunophilin ligands on the allograft rejection in corneal transplantation was examined in the rat. Fisher rat were used as donors and Lewis rats as recipients. This combination caused 100% rejection by 2-3 weeks after surgery as indicated by (1) edema, opacity and neovascularization in the graft, (2) infiltration of a variety of immune cells demonstrated by immunohistological examination and (3) high mixed leukocyte reaction (MLR). Systemic administration o

Topics: Adolescent; Adult; Aged; Animals; Conjunctivitis, Allergic; Corneal Transplantation; Female; Graft Rejection; Humans; Immunosuppressive Agents; Immunotherapy; Male; Middle Aged; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Tacrolimus; Uveitis