tacrolimus and Eye-Diseases

Ocular graft-versus-host disease (GvHD) following allogeneic blood stem cell transplantation leads to immunologically induced alterations in many ocular tissues, particularly at the ocular surface. Within the framework of the main topic, this article focuses primarily on corneal complications in chronic ocular GvHD.. This article aims to promote understanding of the influencing factors, diagnostics, and therapeutic options pertaining to corneal complications in ocular GvHD. Furthermore, the possibilities for prevention are discussed.. This analysis is based on a literature review as well as on data from the Ophthalmology Clinic at the University Hospital Essen.. Corneal complications often occur secondarily in ocular GvHD, as a consequence of severe inflammatory alterations of the conjunctiva or eyelid. Spontaneous corneal perforations associated with only mild symptoms are less common during the course of disease. From the ophthalmologist's perspective, it is important that the inflammatory activity of all the different ocular tissues is considered. Treatment may follow a stepwise scheme that includes substitution, immunosuppression, and surgical rehabilitation.. Systematic diagnosis of ocular GvHD helps to prevent corneal complications or support early therapeutic intervention. An interdisciplinary approach to diagnosis and treatment planning is recommended, in order to optimize local and systemic immunosuppressive therapy.

Topics: Adrenal Cortex Hormones; Chronic Disease; Combined Modality Therapy; Corneal Diseases; Corneal Ulcer; Cyclosporine; Diagnosis, Differential; Eye Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Interdisciplinary Communication; Intersectoral Collaboration; Keratoplasty, Penetrating; Limbus Corneae; Ophthalmic Solutions; Tacrolimus

Tacrolimus (FK506) has been used successfully as a systemic immunomodulator for more than 2 decades, and numerous studies have investigated its mechanisms of action. Systemic and topical tacrolimus have been investigated as treatments for ocular surface disorders that may have an immune-based inflammatory component. In these studies, tacrolimus has shown efficacy in corneal graft rejection, inflammatory conjunctival and corneal diseases, uveitis, and graft-versus-host disease. As these disorders are often refractory to other available treatments, ophthalmic or systemic tacrolimus is a welcome nontoxic adjunct or replacement to potentially toxic topical or systemic immunosuppressive therapies.

Topics: Administration, Topical; Animals; Eye Diseases; Humans; Immunosuppressive Agents; Tacrolimus

Cyclosporine and tacrolimus are potent immunosuppressant agents that have been used extensively in humans, primarily for prevention of transplant rejection but also for the treatment of autoimmune disorders. Both agents have similar mechanisms of action and pharmacokinetic profiles. However, the expected toxicity of the agents is dissimilar. Although cyclosporine usage in veterinary medicine is limited, it has been used enough for therapeutic guidelines to be established. Tacrolimus, however, has undergone limited use in veterinary medicine. The drug is too toxic in dogs for its use to be recommended in most clinical situations. This article reviews the mechanism of action, pharmacokinetics, expected drug interactions and toxicities, and clinical usage of cyclosporine and tacrolimus in veterinary medicine.

Topics: Animals; Autoimmune Diseases; Cat Diseases; Cats; Cyclosporine; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Eye Diseases; Glomerulonephritis; Graft Rejection; Immunosuppressive Agents; Skin Diseases; Tacrolimus; Transplantation

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

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

Poor corneal permeability, nasolacrimal drainage and requirement of chronic administration are major drawbacks of existing therapies for ocular inflammation. Hence, we designed topical micelles of PEG. Integrin targeted tacrolimus loaded PEGCCF micelles (TTM) were prepared by solvent diffusion evaporation method and characterized for particle size, osmolality, encapsulation efficiency and drug loading. Therapeutic potential of TTM was evaluated in benzalkonium chloride induced ocular inflammation model in BALB/c mice. Corneal flourescein staining and histopathological analysis of corneal sections was performed.. TTM had a particle size of 45.3 ± 5.3 nm, encapsulation efficiency (88.7 ± 0.9%w/w) and osmolality of 292-296 mOsmol/Kg. TTM significantly reduced the corneal fluorescence as compared to tacrolimus suspension (TACS). H&E staining showed that TTM could restore corneal epithelial thickness, reduce stromal edema (p < 0.05) and decrease number of inflammatory cells (p < 0.01) compared with TACS. Immunohistochemistry analysis demonstrated lower expression of Ki67 + ve cells (p < 0.05) and IL-6 throughout the cornea against TACS (p < 0.01) and the control (p < 0.001).. TTM is an innovative delivery system for improving ocular inflammation due to a) integrin targeting b) PEGCCF in the form of carrier and c) anti-inflammatory and synergistic effect (due to Pgp inhibition) with TAC.

Topics: Administration, Ophthalmic; Animals; Benzalkonium Compounds; Cholecalciferol; Disease Models, Animal; Drug Carriers; Drug Compounding; Eye; Eye Diseases; Female; Humans; Inflammation; Integrins; Mice; Mice, Inbred BALB C; Micelles; Polyethylene Glycols; Tacrolimus

Severe allergic ocular diseases as atopic keratoconjunctivitis can induce corneal damage due to inflammatory substances released from giant papillae. Tacrolimus eye drops are one of the current therapeutic alternatives for its treatment. This work is aimed at developing and characterizing a 0.03% tacrolimus ophthalmic formulation, which was introduced in three types of vehicles (BBS, PVA and Hyaluronic Acid). For this, we have performed in vitro (stability studies) and in vivo assays (corneal permanence time measured directly by Positron Emission Tomography) of three potential formulations. Next, the best formulation was selected, and its toxicological profile and clinical effectiveness have been evaluated. The biopermanence studies (direct measurements and PET/CT) showed that the formulations with PVA and Hyaluronic Acid present more retention time on the ocular surface of rats than PBS. From the stability study, we have determined that tacrolimus with PVA in cold storage is the best option. Tacrolimus with PVA has shown lower cytotoxicity than cyclosporine at early times. On the other hand, the pilot study performed has shown significant improvements in patients, with no noticeable adverse reactions. Based on stability, biopermanence, safety and clinical effectiveness studies, we concluded that tacrolimus-PVA eye drops are a suitable candidate for its clinical application in inflammatory ophthalmology diseases.

Topics: Administration, Ophthalmic; Adolescent; Adult; Animals; Cell Survival; Child; Cornea; Drug Compounding; Drug Contamination; Drug Stability; Epithelium, Corneal; Eye Diseases; Female; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Immunosuppressive Agents; Male; Ophthalmic Solutions; Osmolar Concentration; Pharmaceutical Vehicles; Pilot Projects; Polyvinyl Alcohol; Positron-Emission Tomography; Pregnancy; Prospective Studies; Rats, Sprague-Dawley; Tacrolimus; Treatment Outcome; Young Adult

Cases are presented of 4 patients suffering from severe symptoms due to ocular psoriasis and who were treated with off-label 0.03% tacrolimus once a day.. All four patients had a mixed blepharitis and keratitis. Pseudopterygium and corneal opacities were present in three of them. All of them experienced an improvement of their itching and ocular surface. They all referred to a marked improvement of their quality of life in a follow-up period ranging from six months to two years. Therefore, topical tacrolimus could be considered an option in the treatment of ocular psoriasis.

Topics: Administration, Topical; Aged; Eye Diseases; Female; Humans; Male; Psoriasis; Tacrolimus

The purpose of this study was to investigate ocular complications among a group of patients on long-term, high-dose immunosuppression and corticosteroids for the maintenance of orthotopic heart transplants. Additionally, we provided information pertinent for the early diagnosis and treatment of eye diseases. In this study, we retrospectively assessed the clinical data of 138 patients with orthotopic heart transplantations from May 2000 to October 2005, including assessment of ophthalmic symptoms and signs, as well as the general condition, treatment, and prognosis. Of 138 transplant recipients examined (276 eyes), 47 eyes (17.0%) showed ocular surface diseases. Sixty-four (23.2%) had a posterior subcapsular cataract, and 16 (5.8%) corticosteroid glaucoma. Fifteen (5.6%) had ocular fundus diseases. Various ocular complications related to immunosuppression and corticosteroids appear among heart transplant patients. Cardiac surgeons and ophthalmologists must closely evaluate ocular symptoms in the posttransplantation period.

Topics: Asian People; Cataract; China; Eye Diseases; Female; Follow-Up Studies; Glaucoma; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Retrospective Studies; Tacrolimus

Ocular involvement in cicatricial pemphigoid often occurs from the onset. Certain forms are seen only in this condition.. A 31-year-old woman presented highly inflammatory conjunctivitis for several months associated with bilateral symblepharons and superficial punctuate keratitis around the left eye refractory to treatment. The patient had a history of mouth ulcers and sores on the scalp. Examination showed scalp lesions with crusts. Histological examination of these lesions revealed dermal-epidermal cleavage. Direct immunofluorescence showed sub-membrane deposits. Anti-basal membrane antibodies were positive. Immunotransfer confirmed the presence of circulating antibodies. This condition was controlled following administration of three courses of cyclophosphamide as a bolus. However, the symblepharons persisted in both eyes. Improvement lasted 4 years. The patient again consulted for inflammatory conjunctivitis and superficial punctate keratitis resulting in invalidating loss of visual acuity, associated with hypereosinophilia. Cortisone eye drops alone resulted in no improvement. Treatment was initiated with topical tacrolimus (Protopic) 0.03% comprising once-daily application to the conjunctiva in the evening. This therapy was well tolerated, and 2 daily applications could be given, followed by a dosage of 0.1%. Improvement was rapid and spectacular, with frank amelioration of visual acuity and resolution of the patient's keratitis. Treatment was continued for 4 months and gradually reduced to the 0.03% dosage level, with increasingly wide intervals between applications. There has been no relapse within the 12 months following the end of treatment.. Standard treatment of pharmacological cicatricial pemphigoid involves systemic immunosuppression since topical anti-inflammatories are ineffective. The mortality associated with this disease is due to iatrogenic complications. Tacrolimus exhibits extremely good penetration of the conjunctiva. Following administration at a concentration of 0.06% 3 times daily in 15 patients with inflammatory disease of the conjunctiva or the cornea, improvement was seen in 10 of these patients at 26 weeks. Tacrolimus appears to act through immunomodulatory and anti-inflammatory mechanisms. It induces local inhibition of T lymphocyte activation and reduces production of pro-inflammatory lymphokines. Oral tacrolimus cannot be used to control cicatricial pemphigoid refractory to standard immunomodulators. However, 3 three other cases involving topical treatment of cicatricial pemphigoid showed marked efficacy of treatment given for 2 to 6 months, with complete tolerability. Thus, topical tacrolimus appears to constitute an interesting alternative treatment in cicatricial pemphigoid.

Topics: Administration, Topical; Adult; Conjunctivitis; Cyclophosphamide; Eye Diseases; Female; Humans; Immunosuppressive Agents; Injections, Intravenous; Keratitis; Lymphocyte Activation; Pemphigoid, Bullous; T-Lymphocytes; Tacrolimus; Time Factors; Tissue Adhesions; Treatment Outcome; Visual Acuity

Topics: Algorithms; Anti-Bacterial Agents; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Dermatologic Agents; Dermatology; Doxycycline; ErbB Receptors; Erlotinib Hydrochloride; Exanthema; Eye Diseases; Female; Humans; Interprofessional Relations; Lung Neoplasms; Medical Oncology; Middle Aged; Ophthalmology; Quinazolines; Referral and Consultation; Skin Diseases; Tacrolimus

Topics: Administration, Topical; Aged; Eye Diseases; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Pemphigoid, Benign Mucous Membrane; Pemphigus; Tacrolimus

Topics: Acute Disease; Adult; Eye Diseases; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Tacrolimus